FN Thomson Reuters Web of Science™ VR 1.0 PT S AU Summers, RM Jerebko, AK Franaszek, M Malley, JD AF Summers, RM Jerebko, AK Franaszek, M Malley, JD BE Lemke, HU Vannier, MW Inamura, K Farman, AG Doi, K TI An integrated system for computer-aided diagnosis in CT colonography: Work-in-progress SO CARS 2001: COMPUTER ASSISTED RADIOLOGY AND SURGERY SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 15th International Congress and Exhibition on Computer Assisted Radiology and Surgery CY JUN 27-30, 2001 CL BERLIN, GERMANY SP Amer Acad Oral & Maxillofacial Radiol, Bulgarian Assoc Radiol, British Inst Radiol, Czech Radiol Soc, Deutsch Gesell Biomed Tech eV, DRG, European Soc Engn & Med, Gesell Informatik, GMDS, Int Assoc Dento Maxillo Facial Radiol, IEEE, Informat Processing Med Imaging, Japanese Coll Radiol, Japan Radiol Soc, Japanese Soc Oral & Maxillofacial Radiol, Nederlandse Vereniging Radiol, ORG, Royal Coll Radiologists, Soc Francaise Radiol Med, Schweizer Gesell Med Radiol, Assoc Italiana Radiol Med, Chinese Soc Comp Assisted Radiol, SPIE, Slovak Radiol Soc, Techn Univ Berlin, World Acad Biomed Technologies DE CT colonography; visualization; image processing; colon cancer; computer-assisted diagnosis ID VIRTUAL BRONCHOSCOPY; DISPLAY; LESIONS AB A high-throughput. integrated software system to investigate computer-aided diagnosis for CT colonography is described and demonstrated. The system allows investigation of numerous parameters and algorithms critical to the goal of automated localization of possible polyps. The system forms the foundation of our future research efforts. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. EM rms@nih.gov NR 12 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50866-X J9 INT CONGR SER JI Int. Congr. Ser. PY 2001 VL 1230 BP 629 EP 634 PG 6 WC Computer Science, Interdisciplinary Applications; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA BT72A UT WOS:000173844800105 ER PT S AU Macura, RT Staab, E Vucich, J Macura, KJ Chang, CI Macura, TJ AF Macura, RT Staab, E Vucich, J Macura, KJ Chang, CI Macura, TJ BE Lemke, HU Vannier, MW Inamura, K Farman, AG Doi, K TI Medical imaging 2001; Haystack is here, but how to find a (relevant) needle? A survey of existing content-based image retrieval systems SO CARS 2001: COMPUTER ASSISTED RADIOLOGY AND SURGERY SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 15th International Congress and Exhibition on Computer Assisted Radiology and Surgery CY JUN 27-30, 2001 CL BERLIN, GERMANY SP Amer Acad Oral & Maxillofacial Radiol, Bulgarian Assoc Radiol, British Inst Radiol, Czech Radiol Soc, Deutsch Gesell Biomed Tech eV, DRG, European Soc Engn & Med, Gesell Informatik, GMDS, Int Assoc Dento Maxillo Facial Radiol, IEEE, Informat Processing Med Imaging, Japanese Coll Radiol, Japan Radiol Soc, Japanese Soc Oral & Maxillofacial Radiol, Nederlandse Vereniging Radiol, ORG, Royal Coll Radiologists, Soc Francaise Radiol Med, Schweizer Gesell Med Radiol, Assoc Italiana Radiol Med, Chinese Soc Comp Assisted Radiol, SPIE, Slovak Radiol Soc, Techn Univ Berlin, World Acad Biomed Technologies C1 NIH, Bethesda, MD 20892 USA. RP Macura, RT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50866-X J9 INT CONGR SER PY 2001 VL 1230 BP 1120 EP 1120 PG 1 WC Computer Science, Interdisciplinary Applications; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA BT72A UT WOS:000173844800207 ER PT J AU Lee, MY Choi, SH Shin, SL Chin, H Kwon, OJ AF Lee, MY Choi, SH Shin, SL Chin, H Kwon, OJ TI Distribution of B/K protein in rat brain SO CELL AND TISSUE RESEARCH LA English DT Article DE B/K protein; antiserum; brain; mapping; immunohistochemistry; rat (Sprague Dawley) ID CA2+-DEPENDENT EXOCYTOSIS; KINASE-C; C-2-DOMAIN PROTEINS; PC12 CELLS; N-COPINE; SYNAPTOTAGMIN; DOMAINS; DOC2; RABPHILIN-3A; MEMBRANE AB B/K protein is a recently isolated member of the double C2-1ike-domain protein family, which is highly abundant in rat brain. We generated high-titer rabbit polyclonal antibodies with specificity to the 55-kDa rat B/K protein, and examined the expression pattern of B/K protein in rat brain using an immunohistochemical staining method. Immunoreactivity to B/K protein was widely found in distinct regions of rat brain: strongly in the hypothalamus, most of the circumventricular organs, the locus coeruleus, the A5 neurons of the pens, and the anterior pituitary; moderately in the anterior olfactory nucleus, the raphe nucleus, the subfornical organ, and the median eminence; and faintly in the olfactory bulb, the telencephalon, the substantia nigra pars compacta, and the ventral tegmental area. In contrast, immunoreactivity to B/K protein was not observed in the thalamus, the cerebellum, the posterior pituitary, or the spinal cord. In most of the B/K-expressing neurons, immunoreactivity was expressed mainly in soma but not in nerve fibers. B/K was also expressed in nonneuronal cells such as the tanycytes and the subcommissural organ. In the vasopressin-secreting supraoptic and paraventricular nuclei of the hypothalamus, the site where B/K cDNA was originally isolated from, all of the neurons showing vasopressin immunoreactivity also expressed B/K protein, suggesting an overlap of their expression patterns. C1 Catholic Univ Korea, Coll Med, Dept Biochem, Seoul 137701, South Korea. Catholic Univ Korea, Coll Med, Dept Anat, Seoul 137701, South Korea. NIMH, Genet Res Branch, Div Neurosci & Basic Behav Sci, NIH, Bethesda, MD 20892 USA. RP Kwon, OJ (reprint author), Catholic Univ Korea, Coll Med, Dept Biochem, 505 Banpo Dong, Seoul 137701, South Korea. NR 25 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD JAN PY 2001 VL 303 IS 1 BP 47 EP 56 DI 10.1007/s004410000221 PG 10 WC Cell Biology SC Cell Biology GA 389RF UT WOS:000166251000005 PM 11236004 ER PT J AU Gmeiner, WH Xu, JZ Horita, DA Smithgall, TE Engen, JR Smith, DL Byrd, RA AF Gmeiner, WH Xu, JZ Horita, DA Smithgall, TE Engen, JR Smith, DL Byrd, RA TI Intramolecular binding of a proximal PPII helix to an SH3 domain in the fusion protein SH3Hck : PPIIhGAP SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE SH3; hydrogen exchange; NMR; mass spectrometry ID HCK TYROSINE KINASE; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURE; CHEMICAL-SHIFTS; LARGER PROTEINS; SRC; HIV-1; NMR; FAMILY; H-1 AB SH3 domains are a conserved feature of many nonreceptor protein tyrosine kinases, such as Hck, and often function in substrate recruitment and regulation of kinase activity. SH3 domains modulate kinase activity by binding to polyproline helices (PPII helix) either intramolecularly or in target proteins. The preponderance of bimolecular and distal interactions between SH3 domains and PPII helices led us to investigate whether proximal placement of a PPII helix relative to an SH3 domain would result in tight, intramolecular binding. We have fused the PPII helix region of human GAP to the C-terminus of Hck SH3 and expressed the recombinant fusion protein in Eschericheria coli. The fusion protein, SH3(Hck) : PPIIhGAP, folded spontaneously into a structure in which the PPII helix was bound intramolecularly to the hydrophobic crevice of the SH3 domain. The SH3Hck: PPIIhGAP fusion protein is useful for investigating SH3 : PPII helix interactions, for studying concepts in protein folding and design, and may represent a protein structural motif that is widely distributed in nature. C1 Wake Forest Univ, Sch Med, Dept Biochem, Winston Salem, NC 27157 USA. Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. Univ Nebraska, Dept Chem, Lincoln, NE 68588 USA. NCI, Struct Biophys Lab, Frederick, MD 21702 USA. RP Gmeiner, WH (reprint author), Wake Forest Univ, Sch Med, Dept Biochem, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA. RI Byrd, R. Andrew/F-8042-2015; OI Byrd, R. Andrew/0000-0003-3625-4232; Horita, David/0000-0002-9563-107X FU NCI NIH HHS [P30 CA36727, CA60612, R01 CA81398]; NCRR NIH HHS [P41 RR002301] NR 32 TC 17 Z9 18 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PY 2001 VL 35 IS 2 BP 115 EP 126 DI 10.1385/CBB:35:2:115 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 494JR UT WOS:000172279400001 PM 11892787 ER PT J AU Duhe, RJ Wang, LH Farrar, WL AF Duhe, RJ Wang, LH Farrar, WL TI Negative regulation of Janus kinases SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Review ID PROTEIN-TYROSINE-PHOSPHATASE; JAK-STAT PATHWAY; SEVERE COMBINED IMMUNODEFICIENCY; SIGNAL-TRANSDUCTION PATHWAY; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PROOPIOMELANOCORTIN GENE-EXPRESSION; SEVERE CONGENITAL NEUTROPENIA; STIMULATED JAK/STAT PATHWAY; LEUKEMIA-INHIBITORY FACTOR; GROWTH-FACTOR INDEPENDENCE AB The precise regulation of both the magnitude and the duration of Janus kinase (JAK) catalytic activity is essential for the cytokine orchestration of many biological processes, and the dysregulation of JAK activity has pathological implications. Immunosuppressive disease states, such as X-linked severe combined immunodeficiency, arise from inappropriate JAK inhibition. In contrast, a limited number of cancers, primarily leukemias, result from constitutive or enhanced activation of JAK activity. JAKs are no longer implicated only in classic cytokine receptor-mediated signaling pathways, but are now also known to integrate indirectly into other receptor-mediated signal transduction processes. Therefore, an increasing number of therapeutic applications exist for biological-response modifiers that can restore aberrant JAK activity to normal levels. Exciting breakthroughs in both physiological and pharmacological methods of selective inhibition of cytokine-JAK-signal transducers and activators of transcription pathways have recently emerged in the form of suppressors of cytokine signaling (also known as cytokine-inducible SH2 protein, JAK-binding protein, or STAT-induced STAT inhibitor) proteins and novel dimethoxyquinazoline derivatives, respectively. The basis of these and other mechanisms of negative regulation of TAK activity, including the suppression of jak expression levels caused by tumor- or pathogen-derived agents, the complex interactions of JAKs with phosphatases, and the redox regulation of JAK catalytic activity, is the focus of this review. C1 Univ Mississippi, Med Ctr, Dept Pharmacol & Toxicol, Jackson, MS 39216 USA. NCI, Cytokine Mol Mech Sect, Mol Immunoregulat Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Duhe, RJ (reprint author), Univ Mississippi, Med Ctr, Dept Pharmacol & Toxicol, Jackson, MS 39216 USA. FU NCI NIH HHS [N01-CO-56000] NR 212 TC 19 Z9 19 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PY 2001 VL 34 IS 1 BP 17 EP 59 DI 10.1385/CBB:34:1:17 PG 43 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 435CW UT WOS:000168860700002 PM 11394440 ER PT J AU Tsai, CJ Nussinov, R AF Tsai, CJ Nussinov, R TI Transient, highly populated, building blocks folding model SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE protein folding; sequential folding; building block; misfolding; funnels; disconnectivity graphs ID PROTEIN-PROTEIN INTERFACES; TRANSITION-STATE; ENERGY LANDSCAPES; SUPERSECONDARY STRUCTURE; SECONDARY STRUCTURE; INITIATION SITES; LOCAL-STRUCTURE; HYDROGEN-BONDS; PEPTIDE MODELS; COMPACT UNITS AB Protein folding is a hierarchical event, in which transiently formed local structural elements assemble to yield the native conformation. In principle, multiple paths glide down the energy landscape, but, in practice, only a few of the paths are highly traveled. Here, the literature is reviewed in this light, and, particularly, a hierarchical, building block protein-folding model is presented, putting it in the context of a broad range of experimental and theoretical results published over the past few years. The model is based on two premises: First, although the local building block elements may be unstable, they nevertheless have higher population times than all alternate conformations; and, second, protein folding progresses through a combinatorial assembly of these elements. Through the binding of the most favorable building block conformers, there is a redistribution of the conformers in solution, propagating the protein-folding reaction. We describe the algorithm, and illustrate its usefulness, then we focus on its utility in assigning simple vs complex folding pathways, on chaperonin-assisted folding, on its relevance to domain-swapping processes, and on its relevance and relationship to disconnectivity graphs and tree diagrams. Considering protein folding as initiating from local transient structural elements is consistent with available experimental and theoretical results. Here, we have shown that, early in the folding process, sequential interactions are likely to take place, even if the final native fold is a complex, nonsequential one. Such a route is favorable kinetically and entropically. Through the construction of anatomy trees, the model enables derivation of the major folding pathways and their bumps, and qualitatively explains the kinetics of protein folding. C1 NCI, Intramural Res Support Program, SAIC Lab Expt & Computat Biol, Frederick, MD 21702 USA. Tel Aviv Univ, Sch Med, Dept Genet, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Intramural Res Support Program, SAIC Lab Expt & Computat Biol, Bldg 469,Rm 151, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 96 TC 8 Z9 8 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PY 2001 VL 34 IS 2 BP 209 EP 235 DI 10.1385/CBB:34:2:209 PG 27 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 451CC UT WOS:000169782700003 PM 11898865 ER PT J AU Hawkins, ME AF Hawkins, ME TI Fluorescent pteridine nucleoside analogs - A window on DNA interactions SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Review ID COLI RNA-POLYMERASE; POLYACRYLAMIDE-GEL ELECTROPHORESIS; OPEN COMPLEX-FORMATION; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; PHOSPHOROTHIOATE OLIGONUCLEOTIDE; RETROVIRAL INTEGRATION; PROMOTER RECOGNITION; GUANOSINE ANALOG; ASSAY; BINDING AB Pteridine nucleoside analog probes are highly fluorescent and offer different approaches to monitor subtle DNA interactions with other molecules. Similarities in structure and size to native nucleosides make it possible to incorporate these probes into oligonucleotides through the standard deoxyribose linkage. These probes are formulated as phosphoramidites and incorporated into oligonucleotides using automated DNA synthesis. Their position within the oligonucleotide renders them exquisitely sensitive to changes in structure as the oligonucleotide meets and reacts with other molecules. Changes are measured through fluorescence intensity, anisotropy, lifetimes, spectral shifts, and energy transfer. The fluorescence properties of pteridine nucleoside analogs as monomers and incorporated into single and double stranded oligonucleotides are reviewed. The two guanosine analogs, 3MI and 6MI, and two adenosine analogs, 6MAP and DMAP, are reviewed in detail along with applications utilizing them. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Hawkins, ME (reprint author), NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NR 40 TC 105 Z9 106 U1 2 U2 18 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PY 2001 VL 34 IS 2 BP 257 EP 281 DI 10.1385/CBB:34:2:257 PG 25 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 451CC UT WOS:000169782700005 PM 11898867 ER PT J AU Chatterjee, B Li, YX Zdanowicz, M Sonntag, JM Chin, AJ Kozlowski, DJ Valdimarsson, G Kirby, ML Lo, CW AF Chatterjee, B Li, YX Zdanowicz, M Sonntag, JM Chin, AJ Kozlowski, DJ Valdimarsson, G Kirby, ML Lo, CW TI Analysis of Cx43 alpha 1 promoter function in the developing zebrafish embryo SO CELL COMMUNICATION AND ADHESION LA English DT Article; Proceedings Paper CT International Gap Junction Conference CY 2001 CL HONOLULU, HAWAII DE connexin 43; neural crest cells; promoter; regulatory sequences; zebrafish development ID GAP JUNCTION GENE; NEURAL CREST CELLS; EXPRESSION; HEART; COMMUNICATION AB The Cx43alpha 1 gap junctions play an important role in cardiovascular development. Studies using transgenic mouse models ha e indicated that this involves an essential role for Cx43alpha 1 in modulating neural crest cell motility. We previously showed that a 6.8 kb mouse genomic sequence containing the promoter and upstream regulatory sequences of the Cx43alpha 1 gene can drive lacZ reporter gene expression in all neural crest cell lineages in the mouse embryo. To obtain further insights into the sequence motifs and regulatory pathways involved in targeting Cx43alpha 1 gene expression in neural crest cells, we assayed the activity of the mouse Cx43alpha 1 promoter in evolutionarily distantly related zebrafish embryos. For these studies, the 6.8kb Cx43alpha 1 genomic sequence and various deletion derivatives were used to generate GFP or lacZ expression vectors. The transcriptional activities of these constructs were analyzed in vivo after microinjection into one- or two- cell stage zebrafish embryos, These Studies indicated that the mouse Cx43alpha 1 promoter can drive lacZ expression in neural crest cells in the zebrafish embryos. Analysis by whole mount in situ hybridization showed that the endogenous zebrafish Cx43alpha 1 gene is expressed maternally and zygotically, and expression is observed in regions where neural crest cells are found. To further elucidate the developmental regulation of Cx43alpha 1 gene expression, we screened a zebrafish BAC library and identified a clone containing the entire zebrafish Cx43alpha 1 gene and flanking upstream and downstream sequences. The Upstream Cx43alpha 1 promoter sequences front zebrafish, mouse, and human were analyzed for evolutionarily conserved DNA motifs. Overall these Studies suggest that the sequence motifs and transcriptional regulation involved in the targeting Cx43alpha 1 expression to neural crest cells are evolutionarily conserved in zebrafish and mouse embryos. C1 Univ Penn, Dept Biol, Philadelphia, PA USA. Duke Univ, Dept Pediat, Durham, NC USA. Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA USA. Univ Penn, Dept Pediat, Philadelphia, PA USA. Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA USA. Univ Penn, Dept Biol, Philadelphia, PA USA. Univ Manitoba, Dept Zool Biochem & Med Genet, Winnipeg, MB R3T 2N2, Canada. Duke Univ, Dept Pediat, Durham, NC USA. Univ Penn, Biol Dept, Philadelphia, PA USA. RP Lo, CW (reprint author), NHLBI, Lab Dev Biol, NIH, 50 S Dr Rm 4537 MSC8019, Bethesda, MD 20814 USA. OI Chin, Alvin/0000-0002-0417-8653 NR 6 TC 5 Z9 5 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-5385 J9 CELL COMMUN ADHES JI Cell Commun. Adhes. PY 2001 VL 8 IS 4-6 BP 289 EP + DI 10.3109/15419060109080739 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 558UD UT WOS:000175984300027 PM 12064604 ER PT J AU Lagostena, L Cicuttin, A Inda, J Kachar, B Mammano, F AF Lagostena, L Cicuttin, A Inda, J Kachar, B Mammano, F TI Frequency dependence of electrical coupling in Deiters' cells of the guinea pig cochlea SO CELL COMMUNICATION AND ADHESION LA English DT Article; Proceedings Paper CT International Gap Junction Conference CY 2001 CL HONOLULU, HAWAII DE caged compounds; cell networks; connexins; electrical models; hearing; organ of Corti; patch clamp; UV photolysis ID OUTER HAIR-CELLS; INTRACELLULAR-RECORDINGS; POTASSIUM CURRENTS; SUPPORTING CELLS; GAP-JUNCTIONS; RAT COCHLEA; EXPRESSION; ORGAN; POTENTIALS; CORTI AB Immunolabeling with antibodies against connexins 26 and 30 shoved that. in the guinea pig cochlea, supporting Deiters' cells are massively interconnected and form an orderly network within the organ of Corti. In paired patch-clamp recordings the coupling ratio (CR) of adjacent Deiters' cells at the apex of the cochlea (similar to0.31) was 3-fold smaller than in isolated cell pairs due to shunting afforded by multicellular connectivity. With sinusoidal current stimuli the delay in signal propagation between adjacent cells increased with increasing frequency whereas the amplitude did not change significantly up to 200 HZ (corner frequency F-c similar to220 Hz). Depolarizing voltage commands applied to an outer hair cell (OHC) elicited outward potassium currents in the OHC and inward currents in the abutting Deiters, cells, supplying direct evidence for potassium buffering in the organ of Corti. Computational analysis indicates that electrical signals injected into a Deiters' cell are transmitted across a network segment spanning 8 cell diameters. Thus electrical coupling in the organ of Corti is unlikely to influence the selectivity of frequency filtering performed mechanically by the mammalian cochlea. C1 Scuola Int Super Studi Avanzati, Biophys Sector, I-34014 Trieste, Italy. Scuola Int Super Studi Avanzati, INFM Unit, I-34014 Trieste, Italy. Abdus Salam Int Ctr Theoret Phys, Ist Nazl Fis Nucl, ICTP, Microprocessor Lab, I-34014 Trieste, Italy. NIDCD, Sect Struct Cell Biol, NIH, Bethesda, MD USA. Scuola Int Super Studi Avanzati, Biophys Sector, I-34014 Trieste, Italy. Scuola Int Super Studi Avanzati, INFM Unit, I-34014 Trieste, Italy. RP Mammano, F (reprint author), Scuola Int Super Studi Avanzati, Biophys Sector, Via Beirut 2-4, I-34014 Trieste, Italy. RI Mammano, Fabio/I-5064-2012 OI Mammano, Fabio/0000-0003-3751-1691 FU NIDCD NIH HHS [Z01 DC 00002-11] NR 16 TC 12 Z9 13 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-5385 J9 CELL COMMUN ADHES JI Cell Commun. Adhes. PY 2001 VL 8 IS 4-6 BP 393 EP 399 DI 10.3109/15419060109080760 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 558UD UT WOS:000175984300048 PM 12064625 ER PT J AU Park, SH Birchenall-Roberts, MC Yi, YS Lee, BI Lee, DK Bertolette, DC Fu, T Ruscetti, F Kim, SJ AF Park, SH Birchenall-Roberts, MC Yi, YS Lee, BI Lee, DK Bertolette, DC Fu, T Ruscetti, F Kim, SJ TI Mechanism of induction of transforming growth factor-beta type II receptor gene expression by v-Src in murine myeloid cells SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID TUMOR-SUPPRESSOR GENE; GASTRIC-CANCER CELLS; ETS ONCOGENE FAMILY; TGF-BETA; TRANSCRIPTION FACTOR; MICROSATELLITE INSTABILITY; MOLECULAR-CLONING; DOMAIN PROTEIN; DPC4 GENE; MEMBER AB Transforming growth factor (TGF)-beta1 plays an important role during hematopoiesis. Previously, we had shown that the growth of a v-Src-transformed myeloid cell line was markedly more inhibited by TGF-beta treatment when compared with the wild-type myeloid cell line. To investigate the increased growth sensitivity of the v-Src-transformed myeloid cell line, 32D-src, to TGF-beta, we examined expression of the TGF-beta type II receptor (TGF-beta RII) gene in myeloid cell lines. Northern blot analysis showed that expression of similar to8- and 6-kb species of TGF-beta RII transcripts was markedly increased in the 32D-src cell line. The expression of the TGF-beta RII promoter linked to a reporter gene was increased 23-fold by v-Src, DNA transfection and electrophoretic mobility shift assay revealed that v-Src induces TGF-beta RII promoter activity through an AP1/ATF2-like sequence (-219 to -172), ETS binding sites (+1 to +36), and the inverted CCAAT box (-81 to -77), Novel DNA-protein complexes with FTS binding sites are significantly increased in v-src-transformed cell lines compared with the control cell line. These results suggest that v-Src induces activity of the TGF-beta RII promoter through multiple elements by inducing expression of nuclear proteins interacting with these elements. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Leukocyte Biol, Frederick, MD 21702 USA. RP Kim, SJ (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Room B1106, Bethesda, MD 20892 USA. NR 48 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JAN PY 2001 VL 12 IS 1 BP 9 EP 18 PG 10 WC Cell Biology SC Cell Biology GA 395RX UT WOS:000166596000002 PM 11205746 ER PT J AU Feng, Y Longo, DL Ferris, DK AF Feng, Y Longo, DL Ferris, DK TI Polo-like kinase interacts with proteasomes and regulates their activity SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID ANAPHASE-PROMOTING COMPLEX; XENOPUS EGG EXTRACTS; CELL-CYCLE; 20S PROTEASOME; PROTEIN-KINASE; PHOSPHORYLATION; MITOSIS; PLX1; SUBUNITS; SPINDLE AB The polo-like kinase (Plk) has been shown to be associated with the anaphase-promoting complex at the transition from metaphase to anaphase and to regulate ubiquitination, the process that targets proteins for degradation by proteasomes. In this study, we have identified proteasomal proteins interacting with Plk by mass spectrometry and found that Plk and 20S proteasome subunits could be reversibly immunoprecipitated from both human CA46 cells and HEK 293 cells transfected with HA-Plk. Furthermore, both coprecipitated Plk and baculovirus-expressed Plk were able to phosphorylate proteasome subunits, and metabolic labeling studies indicate that Plk is partially responsible for the phosphorylation of 20S proteasome subunits C9 and C8 in vivo. In addition, phosphorylation of proteasomes by Plk enhanced proteolytic activity toward an artificial substrate Suc-L-L-V-Y-AMC in vitro and in vivo. Finally, we were also able to detect Plk associated with 26S proteasomes under certain conditions. Together our results suggest that Plk is an important mitotic regulator of proteasome activity. C1 NCI, Frederick Canc Res & Dev Ctr, Biol Mechanisms Sect, Lab Leucocyte Biol, Frederick, MD 21702 USA. NIA, Baltimore, MD 21224 USA. NCI, Frederick Canc Res & Dev Ctr, IRSP, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Ferris, DK (reprint author), NCI, Frederick Canc Res & Dev Ctr, Biol Mechanisms Sect, Lab Leucocyte Biol, Frederick, MD 21702 USA. FU NCI NIH HHS [CA33572, N01CO56000] NR 42 TC 46 Z9 47 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JAN PY 2001 VL 12 IS 1 BP 29 EP 37 PG 9 WC Cell Biology SC Cell Biology GA 395RX UT WOS:000166596000004 PM 11205743 ER PT J AU Borlongan, CV Su, TP Wang, Y AF Borlongan, CV Su, TP Wang, Y TI Delta opioid peptide augments functional effects and intrastriatal graft survival of rat fetal ventral mesencephalic cells SO CELL TRANSPLANTATION LA English DT Article DE Parkinson's disease; neural transplantation; fetal mesencephalic cells; substantia nigra; striatum; 6-hydroxydopamine; tyrosine hydroxylase; locomotor behavior ID NEUROTROPHIC FACTOR; DOPAMINERGIC-NEURONS; FIBER OUTGROWTH; BEHAVIORAL RECOVERY; PARKINSONS-DISEASE; NIGRAL GRAFTS; LINE; TRANSPLANTATION; TISSUE; STRIATUM AB Delta enkephalin analogue [D-Ala(2),D-Leu(5)]enkephalin (DADLE) has been shown to protect dopamine transporters from methamphetamine-induced neurotoxicity. In the present study, we demonstrate that exposure of embryonic ventral mesencephalic cells to DADLE (0.01 g/ml). prior to intrastriatal transplantation. enhanced functional recovery and graft survival in 6-hydroxydopamine-induced hemiparkinsonian rats. At 6 and 8 weeks posttransplantation, animals that received DADLE-treated cell grafts exhibited significantly higher (near normal) spontaneous locomotor behaviors, as well as trends of greater reversal of motor asymmetrical behaviors compared with animals that received nontreated cell grafts. Histological examination revealed that animals transplanted with DADLE-treated cell grafts exhibited about twice the number of surviving tyrosine hydroxylase-immunoreactive grafted neurons compared with those animals that received nontreated cell grafts. These results suggest that DADLE should be considered as an adjunctive agent for neural transplantation therapy in Parkinson's disease. C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Borlongan, CV (reprint author), NIDA, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Borlongan, Cesar/0000-0002-2966-9782 NR 33 TC 19 Z9 19 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD JAN-FEB PY 2001 VL 10 IS 1 BP 53 EP 58 PG 6 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 415VY UT WOS:000167745300006 PM 11294472 ER PT J AU Monga, SPS Tang, Y Candotti, F Rashid, A Wildner, O Mishra, B Iqbal, S Mishra, L AF Monga, SPS Tang, Y Candotti, F Rashid, A Wildner, O Mishra, B Iqbal, S Mishra, L TI Expansion of hepatic and hematopoietic stem cells utilizing mouse embryonic liver explants SO CELL TRANSPLANTATION LA English DT Article DE liver; development; stem cells; culture; explant; gene therapy ID MEDIATED GENE-TRANSFER; HEPATOCYTE TRANSPLANTATION; PROGENITOR CELLS; EXPRESSION; DIFFERENTIATION; IDENTIFICATION; CULTURE; TCF-4; TITER AB Ex vivo embryonic liver explant culture is a novel and attractive approach to obtain abundant hepatic and hematopoietic stem cells. Gene therapy of autologous hepatic and hematopoietic stem cells represents an alternative therapeutic approach to liver transplantation for genetic and metabolic disorders. In this study we characterize the growth and differentiation of hepatic stem cells utilizing embryonic liver cultures. Day 9.5 liver buds are microdissected and cultured under specific conditions. Modulation of growth conditions by addition of hepatocyte growth factor, Flt-3 ligand, and stem cell factor leads to enrichment of hepatic progenitor cells in embryonic liver explants. Under these conditions, we also demonstrate the role of a novel marker PRAJA-1 to identify hepatic stem cells and transitional hepatocytes. Utilization of dexamethasone enhanced pseudolobule formation with increased hepatocytic and biliary differentiation. Transforming growth factor-beta leads to enrichment of biliary cells in the culture, Gut formation is enhanced in the presence of interleukin-3 and blood formation by increasing the mesodermal tissue in these cultures. We also show increased retroviral-mediated expression of the green fluorescent protein expression in the expanded hepatic and hematopoietic stem cells under different culture conditions. Thus, the embryonic liver explant culture is an attractive source for hepatic progenitors and is a possible step towards generating nontumorigenic immortalized hepatocytes with possible transplantation applications. C1 DVAMC, Lab GI Dev & Mol Biol, Washington, DC 20422 USA. Temple Univ, Fels Canc Inst, Philadelphia, PA 19140 USA. NHGRI, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RP Mishra, L (reprint author), DVAMC, Lab GI Dev & Mol Biol, 151 W,50 Irving St NW, Washington, DC 20422 USA. FU NIDDK NIH HHS [1RO1 DK56111, 1RO3DK53861] NR 40 TC 33 Z9 43 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD JAN-FEB PY 2001 VL 10 IS 1 BP 81 EP 89 PG 9 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 415VY UT WOS:000167745300009 PM 11294475 ER PT B AU Hallenbeck, JM AF Hallenbeck, JM BE Choi, DW Dacey, RG Hsu, CY Powers, WJ TI Inflammation - Introduction SO CEREBROVASCULAR DISEASE: MOMENTUM AT THE END OF THE SECOND MILLENNIUM SE AMERICAN HEART ASSOCIATION MONOGRAPH SERIES LA English DT Proceedings Paper CT 21st Princeton Conference on Cerebrovascular Disease CY MAY 07-10, 1998 CL ST LOUIS, MO SP Washington Univ C1 NINCDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Hallenbeck, JM (reprint author), NINCDS, Stroke Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU FUTURA PUBL CO INC PI ARMONK PA 135 BEDFORD RD PO BOX 418, ARMONK, NY 10504-0418 USA BN 0-87993-494-8 J9 AM HEART MONOGR S PY 2001 BP 193 EP 195 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA BT13Q UT WOS:000172045100012 ER PT B AU McLaughlin, AC Ye, FQ Mattay, VS Frank, JA Weinberger, DR AF McLaughlin, AC Ye, FQ Mattay, VS Frank, JA Weinberger, DR BE Choi, DW Dacey, RG Hsu, CY Powers, WJ TI Quantitative measurement of regional blood flow by magnetic resonance with arterial spin tagging SO CEREBROVASCULAR DISEASE: MOMENTUM AT THE END OF THE SECOND MILLENNIUM SE AMERICAN HEART ASSOCIATION MONOGRAPH SERIES LA English DT Proceedings Paper CT 21st Princeton Conference on Cerebrovascular Disease CY MAY 07-10, 1998 CL ST LOUIS, MO SP Washington Univ ID POSITRON EMISSION TOMOGRAPHY; SENSORY STIMULATION; WORKING-MEMORY; PERFUSION; BRAIN; ACTIVATION; RECOVERY; INVERSION; INCREASES; VALUES C1 NIH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP McLaughlin, AC (reprint author), NIH, Clin Brain Disorders Branch, Bldg 10, Bethesda, MD 20892 USA. NR 27 TC 0 Z9 0 U1 0 U2 0 PU FUTURA PUBL CO INC PI ARMONK PA 135 BEDFORD RD PO BOX 418, ARMONK, NY 10504-0418 USA BN 0-87993-494-8 J9 AM HEART MONOGR S PY 2001 BP 307 EP 316 PG 10 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA BT13Q UT WOS:000172045100021 ER PT J AU Miles, EW AF Miles, EW TI Tryptophan synthase: A multienzyme complex with an intramolecular tunnel SO CHEMICAL RECORD LA English DT Article DE tryptophan synthase; substrate channeling; pyridoxal phosphate; multienzyme complex; crystal structure ID INDUCED CONFORMATIONAL-CHANGES; OXINDOLYL-L-ALANINE; ALPHA-SUBUNIT; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; ALPHA(2)BETA(2) COMPLEX; BETA-SUBUNIT; ALPHA-2-BETA-2 COMPLEX; BIENZYME COMPLEX; FLEXIBLE LOOP AB Tryptophan synthase is a classic enzyme that channels a metabolic intermediate, indole. The crystal structure of the tryptophan synthase alpha(2)beta(2) complex from Salmonella typhimurium revealed for the first time the architecture of a multienzyme complex and the presence of an intramolecular tunnel. This remarkable hydrophobic tunnel provides a likely passageway for indole from the active site of the a subunit, where it is produced, to the active site of the beta subunit, where it reacts with L-serine to form L-tryptophan in a pyridoxal phosphate-dependent reaction. Rapid kinetic studies of the wild type enzyme and of channel-impaired mutant enzymes provide strong evidence for the proposed channeling mechanism. Structures of a series of enzyme-substrate intermediates at the alpha and beta active sites are elucidating enzyme mechanisms and dynamics. These structural results are providing a fascinating picture of loops opening and closing, of domain movements, and of conformational. changes in the indole tunnel. Solution studies provide further evidence for ligand-induced conformational changes that send signals between the alpha and beta subunits. The combined results show that the switching of the enzyme between open and closed conformations couples the catalytic reactions at the alpha and beta active sites and prevents the escape of indole. (C) 2001 The Japan Chemical journal Forum and John Wiley Sons, Inc. C1 NIDDKD, Sect Enzyme Struct & Funct, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Miles, EW (reprint author), NIDDKD, Sect Enzyme Struct & Funct, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA. EM EdithM@intra.niddk.nih.gov NR 78 TC 46 Z9 49 U1 2 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1527-8999 J9 CHEM REC JI Chem. Rec. PY 2001 VL 1 IS 2 BP 140 EP 151 PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA 669VT UT WOS:000182371700004 PM 11893063 ER PT J AU Yang, YC Yan, J Churchwell, M Beger, R Chan, PC Doerge, DR Fu, PP Chou, MW AF Yang, YC Yan, J Churchwell, M Beger, R Chan, PC Doerge, DR Fu, PP Chou, MW TI Development of a P-32-postlabeling/HPLC method for detection of dehydroretronecine-derived DNA adducts in vivo and in vitro SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID PYRROLIZIDINE ALKALOID MONOCROTALINE; PROTEIN CROSS-LINKS; AROMATIC-HYDROCARBONS; CARCINOGENIC ACTIVITY; MASS-SPECTROMETRY; LIVER MICROSOMES; MAMMALIAN-CELLS; RAT-LIVER; IN-VITRO; METABOLITE AB Pyrrolizidine alkaloids are naturally occurring genotoxic chemicals produced by a large number of plants. Metabolism of pyrrolizidine alkaloids in vivo and in vitro generates dehydroretronecine (DHR) as a common reactive metabolite. In this study, we report the development of a P-32-postlabeling/HPLC method for detection of (i) two DHR-3'-dGMP and four DHR-3'-dAMP adducts and (ii) a set of eight DHR-derived DNA adducts in vitro and in vivo. The approach involves (1) synthesis of DHR-3'-dGMP, DHR-3'-dAMP, and DHR-3',5'-dG-bisphosphate standards and characterization of their structures by mass and H-1 NMR spectral analyses, (2) development of optimal conditions for enzymatic DNA digestion, adduct enrichment, and P-32-postlabeling, and (3) development of optimal HPLC conditions. Using this methodology, we have detected eight DHR-derived DNA adducts, including the two epimeric DHR-3',5'-dG-bisphosphate adducts both in vitro and in vivo. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Chou, MW (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 72 TC 38 Z9 39 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 2001 VL 14 IS 1 BP 91 EP 100 DI 10.1021/tx000149o PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 393ZW UT WOS:000166500400011 PM 11170512 ER PT J AU Yang, YC Yan, J Doerge, DR Chan, PC Fu, PP Chou, MW AF Yang, YC Yan, J Doerge, DR Chan, PC Fu, PP Chou, MW TI Metabolic activation of the tumorigenic pyrrolizidine alkaloid, riddelliine, leading to DNA adduct formation in vivo SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID RAT-LIVER MICROSOMES; HAMSTER OVARY CELLS; S-PHASE SYNTHESIS; IN-VITRO; AROMATIC-HYDROCARBONS; CARCINOGENIC ACTIVITY; INVIVO TREATMENT; CROSS-LINKING; INVITRO; MOUSE AB Riddelliine is a representative naturally occurring genotoxic pyrrolizidine alkaloid. We have studied the mechanism by which riddelliine induces hepatocellular tumors in vivo. Metabolism of riddelliine by liver microsomes of F344 female rats generated riddelliine N-oxide and dehydroretronecine (DHR) as major metabolites. Metabolism was enhanced when liver microsomes from phenobarbital-treated rats were used. Metabolism in the presence of calf thymus DNA resulted in eight DNA adducts that were identical to those obtained from the reaction of DHR with calf thymus DNA. Two of these adducts were identified as DHR-modified 7-deoxyguanosin-N-2-yl epimers (DHR-3'-dGMP); the other six were DHR-derived DNA adducts, but their structures were not characterized. A similar DNA adduct profile was detected in the livers of female F344 rats fed riddelliine, and a dose-response relationship was obtained for the level of the total (eight) DHR-derived DNA adducts and the level of the DHR-3'-dGMP adducts. These results suggest that riddelliine induces liver tumors in rats through a genotoxic mechanism and the eight DHR-derived DNA adducts are likely to contribute to liver tumor development. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Chou, MW (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 67 TC 62 Z9 63 U1 2 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 2001 VL 14 IS 1 BP 101 EP 109 DI 10.1021/tx000150n PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 393ZW UT WOS:000166500400012 PM 11170513 ER PT J AU Cragg, G Newman, D AF Cragg, G Newman, D TI Nature's bounty SO CHEMISTRY IN BRITAIN LA English DT Article C1 NCI, Fairview Ctr, Natl Prod Branch, Frederick, MD 21702 USA. RP Cragg, G (reprint author), NCI, Fairview Ctr, Natl Prod Branch, Room 206,POB B, Frederick, MD 21702 USA. NR 8 TC 2 Z9 2 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD,, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0009-3106 J9 CHEM BRIT JI Chem. Br. PD JAN PY 2001 VL 37 IS 1 BP 22 EP 26 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 393DD UT WOS:000166453200035 ER PT J AU Belsky, J Friedman, SL Hsieh, KH AF Belsky, J Friedman, SL Hsieh, KH TI Testing a core emotion-regulation prediction: Does early attentional persistence moderate the effect of infant negative emotionality on later development? SO CHILD DEVELOPMENT LA English DT Article ID BEHAVIOR PROBLEMS; AGE 3; TEMPERAMENT; CHILD AB To test the hypothesis that early attentional persistence will moderate the effect of infant negative emotionality on social competence, problem behavior, and school readiness at age 3, data collected as part of the NICHD Study of Early Child Care were subject to structural equation modeling analyses (N = 1,038). Consistent with Eisenberg et al.'s data on older children, high levels of negative emotionality were associated with low levels of social competence only when attentional persistence was poor. No such moderating effects of attentional persistence emerged in the case of behavior problems. And in the case of school readiness, findings indicated that high levels of negative emotionality predicted high levels of school readiness when attentional persistence was high, a result opposite to that found with respect to the prediction of social competence. C1 Univ London Birkbeck Coll, Sch Psychol, London WC1E 7HX, England. NICHHD, Rockville, MD USA. Penn State Univ, University Pk, PA 16802 USA. RP Belsky, J (reprint author), Univ London Birkbeck Coll, Sch Psychol, London WC1E 7HX, England. OI Belsky, Jay/0000-0003-2191-2503 FU NICHD NIH HHS [U10-HD25420] NR 39 TC 83 Z9 83 U1 0 U2 5 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0009-3920 J9 CHILD DEV JI Child Dev. PD JAN-FEB PY 2001 VL 72 IS 1 BP 123 EP 133 DI 10.1111/1467-8624.00269 PG 11 WC Psychology, Educational; Psychology, Developmental SC Psychology GA 405DY UT WOS:000167143800008 PM 11280474 ER PT J AU Janini, GM Issaq, HJ AF Janini, GM Issaq, HJ TI Selection of buffers in capillary zone electrophoresis: Application to peptide and protein analysis SO CHROMATOGRAPHIA LA English DT Article; Proceedings Paper CT Symposium on CE in Biotechnology - Practical Applications for Protein Analysis CY AUG 18, 1999 CL SAN FRANCISCO, CALIFORNIA SP Calif Separat Sci Soc ID MICELLAR ELECTROKINETIC CHROMATOGRAPHY; MODIFIED SILICA CAPILLARIES; ELECTROOSMOTIC FLOW; INFLUENCE MOBILITY; CETYLTRIMETHYLAMMONIUM BROMIDE; SEPARATION EFFICIENCY; NONIONIC SURFACTANT; ISOELECTRIC BUFFERS; MASS-SPECTROMETRY; FUSED-SILICA C1 NCI, SAIC Frederick, Frederick, MD 21702 USA. RP Janini, GM (reprint author), NCI, SAIC Frederick, POB B, Frederick, MD 21702 USA. NR 79 TC 17 Z9 19 U1 0 U2 4 PU VIEWEG PI WIESBADEN PA ABRAHAM-LINCOLN-STRABE 46, POSTFACH 15 47, D-65005 WIESBADEN, GERMANY SN 0009-5893 J9 CHROMATOGRAPHIA JI Chromatographia PY 2001 VL 53 SU S BP S18 EP S26 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 418LC UT WOS:000167892800003 ER PT J AU Stanyon, R Consigliere, S Bigoni, F Ferguson-Smith, M O'Brien, PCM Wienberg, J AF Stanyon, R Consigliere, S Bigoni, F Ferguson-Smith, M O'Brien, PCM Wienberg, J TI Reciprocal chromosome painting between a New World primate, the woolly monkey, and humans SO CHROMOSOME RESEARCH LA English DT Article DE chromosome rearrangements; comparative genomics; in situ hybridization; phylogeny ID IN-SITU HYBRIDIZATION; INSITU SUPPRESSION HYBRIDIZATION; MOLECULAR PHYLOGENY; DNA-SEQUENCES; CEBUS-APELLA; PLATYRRHINI; HOMOLOGIES; KARYOTYPE; FISH; REARRANGEMENTS AB We employed fluorescence-activated chromosome sorting (FACS) to construct chromosome paint sets for the woolly monkey (Lagothrix lagotricha) and then FISH to reciprocally paint human and woolly monkey metaphases. Reciprocal chromosome painting between humans and the woolly monkey allowed us to assign subchromosomal homologies between these species. The reciprocal painting data between humans and the woolly monkey also allow a better interpretation of the chromosomal difference between humans and platyrrhines, and refine hypotheses about the genomic rearrangements that gave origin to the genome of New World monkeys. Paints of woolly monkey chromosomes were used to paint human metaphases and forty-five clear signals were detected. Paints specific to each human chromosome were used to paint woolly monkey metaphases. The 23 human paints gave 39 clear signals on the woolly monkey karyotype. The woolly monkey chromosomes painted by human paints produced 7 associations of segments homologous to human chromosomes or human chromosome segments: 2/16, 3/21, 4/15, 5/7, 8/18, 10/16 and 14/15. A derived translocation between segments homologous to human chromosomes 4 and 15 is a synapomorphic marker linking all Atelines. These species may also be linked by fragmentation of homologs to human 1, 4, and 15. C1 NCI, Basic Res Lab, Mol Cytogenet Sect, Frederick, MD 21702 USA. Univ Genoa, Dept Anthropol Sci, Genoa, Italy. Univ Cambridge, Dept Clin Vet Med, Cambridge CB3 0ES, England. RP Stanyon, R (reprint author), NCI, Basic Res Lab, Mol Cytogenet Sect, Bldg 560, Frederick, MD 21702 USA. OI Stanyon, Roscoe/0000-0002-7229-1092 NR 38 TC 47 Z9 48 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PY 2001 VL 9 IS 2 BP 97 EP 106 DI 10.1023/A:1009274802086 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 420ZP UT WOS:000168036800002 PM 11321373 ER PT S AU Verma, M Wright, GL Hanash, SM Gopal-Srivastava, R Srivastava, S AF Verma, M Wright, GL Hanash, SM Gopal-Srivastava, R Srivastava, S BE Lo, YMD Chiu, RWK Johnson, PJ TI Proteomic approaches within the NCI Early Detection Research Network for the discovery and identification of cancer biomarkers SO CIRCULATING NUCLEIC ACIDS IN PLASMA OR SERUM II SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd International Symposium on Circulating Nucleic Acids in Plasma or Serum held in conjunction with the 6th Annual Scientific Symposium of the Hong-Kong-Cancer-Institute CY FEB 20-21, 2001 CL HONG KONG, PEOPLES R CHINA SP Amersham Pharmacia Biotech (China) Ltd, Appl Biosys Hong Kong Ltd, Aventis Pharma, Bayer Diagnost Ltd, Beckman Coulter Hong Kong Ltd, Cheng Suen Man Shook Fdn, Faulding Pharmaceut (Hong Kong) Ltd, Gene Co Ltd, Lift Technologies (Pacific) Ltd, Roche Diagnost (Hong Kong) Ltd, Sanofi Synthelabo, Springer Verlag Hong Kong Ltd DE biomarkers; EDRN; LCM; MALDI; ProteinChip; proteomics; SELDI ID MASS-SPECTROMETRY; PROTEIN BIOCHIP; ANTIGEN AB In the postgenome era, proteomics provides a powerful approach for the analysis of normal and transformed cell functions, for the identification of disease-specific targets, and for uncovering novel endpoints for the evaluation of chemoprevention agents and drug toxicity. Unfortunately, the genomic information that has greatly expounded the genetic basis of cancer does not allow an accurate prediction of what is actually occurring at the protein level within a given cell type at any given time. The gene expression program of a given cell is affected by numerous factors in the in vivo environment resulting from tissue complexity and organ system orchestration, with cells acting in concert with each other and responding to changes in their microenvironment. Repositories of genomic information can be considered master "inventory lists" of genes and their maps, which need to be supplemented with protein-derived information. The National Cancer Institute's Early Detection Research Network is employing proteomics, or "protein walking", in the discovery and evaluation of biomarkers for cancer detection and for the identification of high-risk subjects. Armed with microdissection techniques, including the use of Laser Capture Microdissection (LCM) to procure pure populations of cells directly from human tissue, the Network is facilitating the development of technologies that can overcome the problem of tissue heterogeneity and address the need to identify markers in easily accessible biological fluids. Proteomic approaches complement plasma-based assays of circulating DNA for cancer detection and risk assessment. LCM, coupled with downstream proteomics applications, such as two-dimensional polyacrylamide gel electrophoresis and SELDI (surface enhanced laser desorption ionization) separation followed by mass spectrometry (MS) analysis, may greatly facilitate the characterization and identification of protein expression changes that track normal and disease phenotypes. We highlight recent work from Network investigators to demonstrate the potential of proteomics to identify proteins present in cancer tissues and body fluids that are relevant for cancer screening. C1 NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Rockville, MD 20852 USA. Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, Norfolk, VA 23501 USA. Eastern Virginia Med Sch, Virginia Prostrate Ctr, Norfolk, VA 23501 USA. Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. NCI, Div Extramural Activ, Bethesda, MD 20892 USA. RP Srivastava, S (reprint author), NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, 6130 Execut Blvd,EPN-330F, Rockville, MD 20852 USA. NR 24 TC 74 Z9 84 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-378-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 945 BP 103 EP 115 PG 13 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BT32H UT WOS:000172648500013 PM 11708463 ER PT J AU Yoshikawa, T Black, JB Ihira, M Suzuki, K Suga, S Iida, K Saito, Y Asonuma, K Tanaka, K Asano, Y AF Yoshikawa, T Black, JB Ihira, M Suzuki, K Suga, S Iida, K Saito, Y Asonuma, K Tanaka, K Asano, Y TI Comparison of specific serological assays for diagnosing human herpesvirus 6 infection after liver transplantation SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; EXANTHEM-SUBITUM; IDENTIFICATION; PNEUMONITIS; ANTIBODIES; RECIPIENTS; EXCRETION; FEATURES; CHILDREN; TYPE-6 AB Cross-reactivity between human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) antibodies and the reliability of specific serological assays were analyzed for 12 patients with concurrent HHV-6 and HHV-7 antibody responses after transplantation with a liver from a living relative by using an immunofluorescence assay (IFA). A neutralizing antibody titer assay (NT) and an immunoblot assay (IB) designed to detect immunoglobulin M (IgM) antibody to the HHV-6 immunodominant 101-kDa protein were compared in the diagnosis of an active HHV-6 infection. A total of 9 of 12 patients demonstrated concurrent HHV-6 and HHV-7 antibody responses, including increased Ige titers and/or the presence of IgM by IFA, and were thus analyzed for cross-reactive antibody to heterologous virus. The average percentages of residual antibody to HHV-6 and HHV-7 after absorption with HHV-6 antigen were 32.6% (range, 6 to 50%) and 55.6% (range, 35 to 100%), respectively. All 12 patients were subsequently analyzed for HHV-6 antibody by using IB and NT, IB detected IgM antibody to the 101-kDa protein in 75% (9 of 12) of the recipients. A significant rise in the NT antibody titer was detected in the same nine samples. However, HHV-6 DNA was detected by PCR in only five of nine plasma samples collected from recipients with a specific serologic response against HHV-6. C1 Fujita Hlth Univ, Sch Med, Dept Pediat, Aichi, Japan. Special Reference Labs Inc, Tokyo, Japan. Kyoto Univ, Sch Med, Dept Transplantat & Immunol, Kyoto 606, Japan. NCI, NIH, Bethesda, MD 20892 USA. RP Yoshikawa, T (reprint author), Nagoya Univ, Sch Med, Res Inst Dis Mechanism & Control, Virol Lab,Showa Ku, Tsurumai Cho, Nagoya, Aichi 4668550, Japan. RI Asano, Yoshizo/F-6870-2012 NR 29 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JAN PY 2001 VL 8 IS 1 BP 170 EP 173 DI 10.1128/CDLI.8.1.170-173.2001 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 389YG UT WOS:000166265800026 PM 11139213 ER PT B AU Emanuel, EJ AF Emanuel, EJ BE VanderHeide, A OnwuteakaPhilipsen, B Emanuel, EJ VanderMaas, PJ VanderWal, G TI Euthanasia and physician-assisted suicide in the United States at the turn of the 21(st) century SO CLINICAL AND EPIDEMIOLOGICAL ASPECTS OF END-OF-LIFE DECISION-MAKING SE KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN, VERHANDELINGEN LA English DT Proceedings Paper CT Colloquium on Clinical and Epidemiological Aspects of End-of-Life Decision-Making CY OCT 07-09, 1999 CL AMSTERDAM, NETHERLANDS SP Royal Netherlands Acad Arts & Sci, Netherlands Org Sci Res, Dutch Canc Soc, Dutch Minist Hlth, Erasmus Univ Rotterdam Fdn Vereniging Trustfonds, Vrije Univ Amsterdam, VanCoeverden Adriani Fdn & Dittmerfonds, Erasmus Univ Rotterdam, Dept Publ Hlth, Vrije Univ Amsterdam, Fac Med ID ONCOLOGY PATIENTS; WASHINGTON-STATE; ATTITUDES; LIFE; OREGON; NETHERLANDS; DEATH; END; EXPERIENCES; WILLINGNESS AB For more than a decade, the ethics and legality of euthanasia and physician-assisted suicide have been actively debated in the United States. This debate has fairly clearly settled the legal questions and added significant empirical data to inform the debate. This chapter gives a review of both the legal decisions and legislative initiatives regarding euthanasia and physician-assisted suicide and the many empirical studies of the American public, physicians, and patients related to their attitudes and experiences regarding euthanasia and physician-assisted suicide. In 1997, the United States Supreme Court definitively ruled 9-0 that there is no constitutional right to either euthanasia or physician-assisted suicide. But it also made clear that there is no constitutional barrier for states to legalize euthanasia or physician-assisted suicide. Only Oregon has legalized physician-assisted suicide; many other states have passed laws to ensure euthanasia and physician-assisted suicide are illegal. The most recent referendum, in 1998 in Michigan, voted overwhelmingly to oppose legalizing physician-assisted suicide. Data on the public's attitudes shows that support for euthanasia and/or physician-assisted suicide is variable with a majority supporting these interventions for patients in extreme pain but not for other reasons. The elderly, African-Americans, Catholics, and religious individuals are much more likely to oppose euthanasia and physician-assisted suicide. Most surveys of physicians show a majority oppose euthanasia or physician-assisted suicide, with considerable variation among specialties. Support for these interventions among physicians appears to have declined in recent years. About a quarter of physicians, and as many as half of oncologists, have received requests for euthanasia or physician-assisted suicide, but a small minority, less than 10% of all physicians and fewer than 20% of oncologists, have performed euthanasia or physician-assisted suicide. And the physicians who have performed these interventions do them very rarely: most only once in a career. Data from cancer, HIV/AIDS, amyotrophic lateral sclerosis (ALS), and terminally ill patients suggest that depression, hopelessness, and psychological distress are the primary factors associated with personal interest in euthanasia or physician-assisted suicide. Pain, which is the reason most Americans find euthanasia and physician-assisted suicide acceptable-does not appear to be a main motivating factor behind patients' personal desire for euthanasia or physician-assisted suicide. It appears that considerably less than 1% of all Americans die from euthanasia or physician-assisted suicide. Over the last decade the legality of euthanasia and physician-assisted suicide in the United States has been resolved. Empirical research has contributed significantly to our understanding of the attitudes and practices regarding euthanasia and physician-assisted suicide, especially the depth of public support, the factors associated with patient interest, and physician practices regarding euthanasia and physician-assisted suicide. However, several important questions remain unanswered. C1 NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. NR 47 TC 0 Z9 0 U1 2 U2 16 PU ROYAL NETHERLANDS ACADEMY ARTSSCIENCES PI AMSTERDAM PA OUDE HOOGSTRAAT 24 PO BOX 19121, 1000 GC AMSTERDAM, NETHERLANDS BN 90-6984-309-9 J9 KNAW VERHAN PY 2001 VL 102 BP 91 EP 108 PG 6 WC Medical Ethics; Medicine, General & Internal SC Medical Ethics; General & Internal Medicine GA BU30Q UT WOS:000175616200008 ER PT J AU Lammas, DA de Jong, R Ottenhoff, HM Dorman, SE Holland, SM Altare, F Casanova, JL Kumararatne, DS AF Lammas, DA de Jong, R Ottenhoff, HM Dorman, SE Holland, SM Altare, F Casanova, JL Kumararatne, DS TI Type-1 cytokines are essential for effective anti-mycobacterial immunity SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Meeting Abstract C1 Univ Birmingham, MRC, Ctr Immunoregulat, Birmingham B15 2TT, W Midlands, England. Leiden Univ, Med Ctr, Dept Immunohaematol & Bloodbank, NL-2300 RA Leiden, Netherlands. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Hop Necker Enfants Malad, Unite Immunol & Haematol Paediat, Paris, France. Hop Necker Enfants Malad, INSERM, U429, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD JAN PY 2001 VL 31 IS 1 MA W4 BP 156 EP 156 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 410HN UT WOS:000167434700027 ER PT J AU Wood, P Lammas, D Casanova, JL Holland, S Kumararatne, D AF Wood, P Lammas, D Casanova, JL Holland, S Kumararatne, D TI Genetic defects of the Th1 cytokine pathway does not predispose to atopic disease SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Meeting Abstract C1 Univ Birmingham, Dept Immunol, Birmingham B15 2TT, W Midlands, England. Hop Necker Enfants Malad, Unite Immunol, Paris, France. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD JAN PY 2001 VL 31 IS 1 MA W5 BP 157 EP 157 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 410HN UT WOS:000167434700028 ER PT J AU Robey, RW Medina-Perez, WY Nishiyama, K Lahusen, T Miyake, K Litman, T Senderowicz, AM Ross, DD Bates, SE AF Robey, RW Medina-Perez, WY Nishiyama, K Lahusen, T Miyake, K Litman, T Senderowicz, AM Ross, DD Bates, SE TI Overexpression of the ATP-binding cassette half-transporter, ABCG2 (MXR/BCRP/ABCP1), in flavopiridol-resistant human breast cancer cells SO CLINICAL CANCER RESEARCH LA English DT Article ID DEPENDENT KINASE INHIBITOR; MULTIDRUG-RESISTANCE; DRUG-SENSITIVITY; CARCINOMA CELLS; PROTEIN GENE; CYCLE ARREST; APOPTOSIS; EXPRESSION; LINES; CYTOTOXICITY AB We sought to characterize the interactions of flavopiridol with members of the ATP-binding cassette (ABC) transporter family, Cells overexpressing multidrug resistance-1 (MDR-1) and multidrug resistance-associated protein (MRP) did not exhibit appreciable flavopiridol resistance, whereas cell lines overexpressing the ABC half-transporter, ABCG2, (MXR/BCRP/ABCP1), were found to be resistant to flavopiridol, Flavopiridol at a concentration of 10 muM was able to prevent MRP-mediated calcein efflux, whereas Pgp-mediated transport of rhodamine 123 was unaffected at flavopiridol concentrations of up to 100 muM. To determine putative mechanisms of resistance to flavopiridol, we exposed the human breast cancer cell line MCF-7 to incrementally increasing concentrations of flavopiridol, The resulting resistant subline, MCF-7 FLV1000, is maintained in 1000 nM flavopiridol and was found to be 24-fold resistant to flavopiridol, as well as highly cross-resistant to mitoxantrone (675-fold), topotecan (423-fold), and SN-38 (950-fold), the active metabolite of irinotecan, Because this cross-resistance pattern is consistent with that reported for ABCG2-overexpressing cells, cytotoxicity studies were repeated in the presence of 5 muM Of the ABCG2 inhibitor fumitremorgin C (FTC), and sensitivity of MCF-7 FLV1000 cells to flavopiridol, mitoxantrone, SN-38, and topotecan was restored. Mitoxantrone efflux studies were performed, and high levels of FTC-reversible mitoxantrone efflux were found. Northern blot and PCR analysis revealed overexpression of the ABCG2 gene. Western blot confirmed overexpression of ABCG2; neither P-glycoprotein nor MRP overexpression was detected. These results suggest that ABCG2 plays a role in resistance to flavopiridol. C1 NCI, Med Branch, Dev Therapeut Dept, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Mol Therapeut Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. Baltimore Vet Med Ctr, Dept Vet Affairs, Baltimore, MD 21201 USA. RP Bates, SE (reprint author), NCI, Med Branch, Dev Therapeut Dept, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. FU NCI NIH HHS [R01-CA77545] NR 36 TC 255 Z9 266 U1 1 U2 14 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN PY 2001 VL 7 IS 1 BP 145 EP 152 PG 8 WC Oncology SC Oncology GA 395RR UT WOS:000166595500020 PM 11205902 ER PT J AU Takebayashi, Y Goldwasser, F Urasaki, Y Kohlhagen, G Pommier, Y AF Takebayashi, Y Goldwasser, F Urasaki, Y Kohlhagen, G Pommier, Y TI Ecteinascidin 743 induces protein-linked DNA breaks in human colon carcinoma HCT116 cells and is cytotoxic independently of topoisomerase I expression SO CLINICAL CANCER RESEARCH LA English DT Article ID CARIBBEAN TUNICATE; ANTITUMOR-ACTIVITY; ANTICANCER DRUG; CRYSTAL-STRUCTURES; STRAND BREAKS; MINOR-GROOVE; CAMPTOTHECIN; VITRO; TURBINATA; CANCER AB Ecteinascidin 743 (Et743; NSC 648766) is a potent antitumor agent presently in clinical trials. Et743 selectively alkylates guanine N2 from the minor groove of duplex DNA and bends the DNA toward the major groove. This differentiates Et743 from other DNA-alkylating agents presently in the clinic. To date, the cellular effects of Et743 have not been elucidated. Recently, Et743 DNA adducts have been found to suppress gene expression selectively and to induce topoisomerase I (top1) cleavage complexes in vitro and top1-DNA complexes in cell culture. In the present study, we characterized the DNA damage and the cell cycle response induced by Et743 in human colon carcinoma HCT116 cells. Alkaline elution experiments demonstrated that micromolar concentrations of Et743 produced comparable frequencies of DNA-protein cross-links and DNA single-strand breaks, The single-strand breaks were protein-cross-linked and were not associated with detectable DNA double-strand breaks. By contrast with camptothecin, these lesions persisted for several hours after drug removal and were not formed at 4 degreesC. Et743 treatment induced transient p53 elevation, dose-dependent cell cycle accumulation in G(2)-M and in G(1)- and S-phase, and inhibition of DNA synthesis, The sensitivity of camptothecin-resistant mouse leukemia P388/CPT45 cells, which fail to express detectable top1, was similar to the sensitivity of wild-type P388 cells, suggesting that top1 is not a critical target for the antiproliferative activity of Et743. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bldg 37,Room 4E28, Bethesda, MD 20892 USA. NR 32 TC 54 Z9 59 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN PY 2001 VL 7 IS 1 BP 185 EP 191 PG 7 WC Oncology SC Oncology GA 395RR UT WOS:000166595500025 PM 11205907 ER PT J AU Shaker, MR Yang, G Timme, TL Park, SH Kadmon, D Ren, CZ Ji, XR Lee, HM Sehgal, I Anzano, M Sporn, MB Thompson, TC AF Shaker, MR Yang, G Timme, TL Park, SH Kadmon, D Ren, CZ Ji, XR Lee, HM Sehgal, I Anzano, M Sporn, MB Thompson, TC TI Dietary 4-HPR suppresses the development of bone metastasis in vivo in a mouse model of prostate cancer progression SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE bone metastasis; chemoprevention; prostate cancer; retinoids ID LOBUND-WISTAR RATS; CARCINOGENESIS; PREVENTION; SYSTEM; ACID AB The effects of the synthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR) on prostate cancer metastasis in vivo were evaluated in the mouse prostate reconstitution (MPR) model. MPRs were produced by infection of either heterozygous (+/-) or nullizygous (-/-) p53-mutant fetal prostatic epithelial cells with the recombinant retrovirus Zipras/myc 9. Previous studies have documented that loss of p53 function potentiates metastasis in this model system. MPRs were grafted into homozygous (+/+) p53 male mice, fed a 4-HPR containing diet or a control diet and maintained until the status of tumor progression dictated sacrifice. Under these experimental conditions, treatment with 4-HPR did not have a significant effect on primary tumor wet weight for either p53 +/- or p53 -/- MPRs. For, p53 +/- MPRs the animals fed the 4-HPR diet had a slight improvement in survival and a significant reduction in the number of mesenteric metastases (P=0.0477, t-test). Notably, in p53 +/- MPRs the incidence of metastasis to lumbar spine and sternum was 92% in the control animals compared to 54% in the 4-HPR treated animals (P = 0.035, chi (2)-test). In p53 -/- MPRs there was a trend toward a reduction in the number of soft tissue metastases to lung and liver in the 4-HPR group relative to the control diet group and a statistically significant reduction in the incidence of metastasis to bone was demonstrated in that 50% of control animals versus 30% of 4-HPR treated p53 -/- animals harbored bone metastases (P = 0 < 0.05, chi (2)-test). Cell lines were established from portions of the primary tumor and from selected metastatic deposits in each experimental group. Clonal analysis, by retroviral integration pattern, indicated increased clonal diversity in both the primary tumors and metastasis-derived cell lines from 4-HPR treated animals relative to the control animals. In vitro treatment with 4-HPR did not reveal discriminating differences between cell lines derived from primary tumors and bone metastases or control and treatment groups in regard to growth arrest or apoptotic responses. Overall these studies indicate limited anti-tumor and anti-metastatic activity in this highly aggressive in vivo mouse model of prostate cancer, yet 4-HPR treatment significantly suppressed the development of bone metastases in p53 +/- and p53 -/- MPRs revealing a novel and potentially clinically useful activity of this retinoid. C1 Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Radiotherapy, Houston, TX 77030 USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pharmacol, Hanover, NH 03756 USA. Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Thompson, TC (reprint author), Baylor Coll Med, Scott Dept Urol, 6560 Fannin,Suite 2100, Houston, TX 77030 USA. NR 22 TC 4 Z9 4 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 2001 VL 18 IS 5 BP 429 EP 438 PG 10 WC Oncology SC Oncology GA 441BB UT WOS:000169210200011 ER PT J AU Ortmann, RA Shevach, EM AF Ortmann, RA Shevach, EM TI Susceptibility to collagen-induced arthritis: Cytokine-mediated regulation SO CLINICAL IMMUNOLOGY LA English DT Article DE collagen-induced arthritis; cytokines; MHC restriction; Th1/Th2 cells; knockout mice ID RECEPTOR-DEFICIENT MICE; II COLLAGEN; IFN-GAMMA; INTERFERON-GAMMA; AUTOIMMUNE ENCEPHALOMYELITIS; ANTIBODY; DISEASE; INTERLEUKIN-10; PROGRESSION; INDUCTION AB Collagen-induced arthritis is an animal model of inflammatory polyarthritis that is induced in susceptible strains of rats and mice by intradermal immunization with heterologous type II collagen emulsified in complete Freund's adjuvant. Previous studies have demonstrated that disease induction is highly MHC-restricted, with only mice of H-2(q) or H-2(r) haplotypes being susceptible. We have used a panel of both susceptible and resistant strains of mice in which either IFN-gamma or IL-10 signaling has been abolished by gene deletion and show that disease can be readily induced in several resistant strains of the H-2(b) and H-2(d) haplotype; susceptibility was highly dependent on IL-12. IL-4 was also shown to be crucial for disease induction in this model. These results suggest that both Th1 and Th2 cytokines may be important in the etiopathogenesis of disease and that disease susceptibility may be a function of a dysregulated cytokine environment. (C) 2000 Academic Press. C1 NIAID, Cellular Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Ortmann, RA (reprint author), NIAID, Cellular Immunol Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 40 TC 43 Z9 46 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JAN PY 2001 VL 98 IS 1 BP 109 EP 118 DI 10.1006/clim.2000.4961 PG 10 WC Immunology SC Immunology GA 391BN UT WOS:000166334400015 PM 11141333 ER PT J AU Groll, AH Walsh, TJ AF Groll, AH Walsh, TJ TI Uncommon opportunistic fungi: new nosocomial threats SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Review ID BONE-MARROW TRANSPLANT; IN-VITRO ACTIVITY; PENICILLIUM-MARNEFFEI INFECTION; HUMAN-IMMUNODEFICIENCY-VIRUS; TRICHODERMA-LONGIBRACHIATUM INFECTION; BLASTOSCHIZOMYCES-CAPITATUS INFECTION; APIOSPERMUM PSEUDALLESCHERIA-BOYDII; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; PAECILOMYCES SPECIES INFECTIONS; CHRONIC GRANULOMATOUS-DISEASE AB During the past two decades opportunistic fungal infections have emerged as important causes of morbidity and mortality in patients with severe underlying illnesses and compromised host defenses. While Aspergillus and Candida spp. collectively account for the majority of these infections, recent epidemiological trends indicate a shift towards infections by Aspergillus spp., nonalbicans,rs Candida spp., as well as previously uncommon opportunistic fungi. Apart from an expanding number of different Zygomycetes, previously uncommon hyaline filamentous fungi (such as Fusarium species, Acremonium species, Paecilomyces species, Pseudallescheria boydii, and Scedosporium prolificans), dematiaceous filamentous fungi (such as Bipolaris species, Cladophialophora hantiana, Dactylaria gallopava. Exophiala species, and Alternaria species) and yeast-like pathogens (such as Trichosporon species, Blastoschizomyces capitatus, Malassezia species, Rhodotorula rubra and others) are increasingly encountered as causing life threatening invasive infections that are often refractory to conventional therapies. On the basis of past and current trends, the spectrum of fungal pathogens will continue to evolve in the setting of an expanding population of immunocompromised hosts. selective antifungal pressures, and shifting conditions in hospitals and the environment. An expanded and refined drug arsenal, further elucidation of pathogenesis and resistance mechanisms, establishment of in vitro/in vivo correlations, incorporation of pharmacodynamics, combination- and immunotherapies offer hope for substantial progress in prevention and treatment. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Groll, AH (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,Room 13 N-240, Bethesda, MD 20892 USA. NR 205 TC 162 Z9 172 U1 8 U2 18 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PY 2001 VL 7 SU 2 BP 8 EP 24 DI 10.1111/j.1469-0691.2001.tb00005.x PG 17 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 430YH UT WOS:000168602700004 PM 11525222 ER PT J AU Dickerman, RD Jaikumar, S AF Dickerman, RD Jaikumar, S TI The hiccup reflex arc and persistent hiccups with high-dose anabolic steroids: Is the brainstem the steroid-responsive locus? SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE androgens; brainstem; steroid receptors; testosterone; vagus nerve ID INTRACTABLE HICCUPS; DISEASE AB Hiccups have been classified as a neurologic reaction triggered by a multitude of factors. There are only a few reports of persistent hiccups associated with oral and intravenous corticosteroid use in the medical literature. It has been proposed that corticosteroids lower the threshold for synaptic transmission in the midbrain and directly stimulate the hiccup reflex are. There is a recent report of progesterone-induced hiccups, which were thought to occur secondary to the glucocorticoid-like effects of progesterone on the brainstem. We report the first case of anabolic steroid-induced hiccups occurring in an elite power lifter. The hiccups occurred within 12 hours of the individual increasing his doses of oral anabolic steroids and persisted for 12 consecutive hours until medical attention was sought. In this report the pathophysiology of anabolic steroid-induced hiccups is discussed,and the postulated relationships of steroids and the hiccup reflex arc reviewed. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Dickerman, RD (reprint author), Long Isl Jewish Med Ctr, Dept Neurosurg, 410 Lakeville Rd,Suite 210, New Hyde Park, NY 11042 USA. NR 14 TC 13 Z9 17 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD JAN-FEB PY 2001 VL 24 IS 1 BP 62 EP 64 DI 10.1097/00002826-200101000-00011 PG 3 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 405CC UT WOS:000167138800010 PM 11290884 ER PT J AU Ziemann, U Hallett, M AF Ziemann, U Hallett, M TI Hemispheric asymmetry of ipsilateral motor cortex activation during unimanual motor tasks: further evidence for motor dominance SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE ipsilateral motor cortex; inter-hemispheric inhibition; motor dominance; transcranial magnetic stimulation; motor evoked potentials ID TRANSCRANIAL MAGNETIC STIMULATION; EVOKED-POTENTIALS; HUMAN-BRAIN; INTERHEMISPHERIC INHIBITION; DIFFERENT COMPLEXITIES; VOLUNTARY CONTRACTION; CUTANEOUS STIMULI; FINGER MOVEMENTS; HUMAN HANDEDNESS; HAND PREFERENCE AB Objectives: To test to which extent the increase in ipsilateral motor cortex excitability during unimanual motor tasks shows hemispheric asymmetry. Methods: Six right-handed healthy subjects performed one of several motor tasks of different complexity (including rest) with one hand (task hand) while the other hand (non-task hand) was relaxed. Focal transcranial magnetic stimulation was applied to the motor cortex ipsilateral to the task hand and the amplitude of the motor evoked potential (MEP) in the non-task hand was measured. In one session, the task hand was the right hand, in the other session it was the left hand. Thr effects of motor task and side of the task hand were analyzed. Spinal motoneuron excitability was assessed using F-wave measurements. Results: Motor tasks, in particular complex finger sequences, resulted in an increase in MEP amplitude in the non-task hand. This increase was significantly less when the right hand rather than the left hand was the task hand. This difference was seen only in muscles homologous to primary task muscles. The asymmetry could not be explained by changes in F-wave amplitudes. Conclusions: Hemispheric asymmetry of ipsilateral motor cortex activation either supports the idea that, in right handers, the left motor cortex is more active in ipsilateral hand movements, or alternatively, that the left motor cortex exerts more effective inhibitory control over the right motor cortex than vice versa. We suggest that hemispheric asymmetry of ipsilateral motor cortex activation is one property of motor dominance of the left motor cortex. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Frankfurt, Neurol Clin, D-60590 Frankfurt, Germany. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Ziemann, U (reprint author), Univ Frankfurt, Neurol Clin, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. NR 50 TC 108 Z9 111 U1 0 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD JAN PY 2001 VL 112 IS 1 BP 107 EP 113 DI 10.1016/S1388-2457(00)00502-2 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 396TE UT WOS:000166652000014 PM 11137667 ER PT J AU Mima, T Matsuoka, T Hallett, M AF Mima, T Matsuoka, T Hallett, M TI Information flow from the sensorimotor cortex to muscle in humans SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE EEG; EMG; coherence; directed transfer function ID MOTOR CORTEX; 40 HZ; COHERENCE; EEG; SYNCHRONIZATION; PROPAGATION; CONTRACTION; RHYTHM; TREMOR; TASK AB Objectives: To investigate the physiologic mechanism of human electroencephalogram-electromyogram (EEG-EMG) coherence, the directed transfer function (DTF) based on a multivariate autoregressive (MVAR) model was computed. Methods: Fifty-sis channel EEG and EMG of the right abductor pollicis brevis muscle during a weak tonic contraction were recorded in 6 normal volunteers. The EEG over the left sensorimotor area and the rectified EMG were used to compute coherence and DTF. Results: EEG-EMG coherence was observed at the peak frequency of 15-29 Hz (mean 18.5 Hz). The peak frequency of DTF from EEG to EMG was 12-27 Hz (mean 17.8 Hz). DTF from EEG to EMG was significantly larger than that from EMG to EEG at 19-30 and 45-50 Hz (P < 0.05). Conclusions: The present findings suggest that the EEG-EMG coupling mechanism for the 19 Hz or higher frequency might differ from that for the lower frequency. Directional information Row from EEG to EMG in the former frequency range likely reflects the motor control command. The finding of the directional information flow from EEG to EMG within the gamma band indicates that 40 Hz EEG-EMG coherence is not specific to the muscle Piper rhythm which is seen only with strong contraction. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC1428, Bethesda, MD 20892 USA. OI Mima, Tatsuya/0000-0001-7783-1599; Mima, Tatsuya/0000-0001-7787-4855 NR 20 TC 64 Z9 66 U1 2 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD JAN PY 2001 VL 112 IS 1 BP 122 EP 126 DI 10.1016/S1388-2457(00)00515-0 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 396TE UT WOS:000166652000016 PM 11137669 ER PT J AU Sokoloff, L AF Sokoloff, L TI Obituary - Seymour S. Kety, MD 1915-2000 SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Biographical-Item C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. RP Sokoloff, L (reprint author), NIMH, Cerebral Metab Lab, Bldg 36,Room 1A-07, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD JAN PY 2001 VL 1 IS 1-2 BP 2 EP 5 AR PII S1566-2772(00)00021-9 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 529EZ UT WOS:000174288200002 ER PT J AU Hamilton, CS Swedo, SE AF Hamilton, CS Swedo, SE TI Autoimmune-mediated, childhood onset Obsessive-compulsive Disorder and tics: a review SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article DE pediatric autoimmune neuropsychiat disorders assoicated with streptococcal infections; obsessive-compulsive disorder; tics; streptococcal infection; autoimmune response ID ACUTE RHEUMATIC-FEVER; LYMPHOCYTE ANTIGEN D8/17; GROUP-A STREPTOCOCCI; SYDENHAMS-CHOREA; BASAL GANGLIA; NEUROPSYCHIATRIC DISORDERS; TOURETTES-SYNDROME; ANTINEURONAL ANTIBODIES; HUNTINGTONS-DISEASE; CHILDREN C1 NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. RP Hamilton, CS (reprint author), 10 Ctr Dr,Bldg 10,Room 4N208, Bethesda, MD 20892 USA. EM hamiltoe@intra.nimh.nih.gov NR 93 TC 5 Z9 5 U1 6 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD JAN PY 2001 VL 1 IS 1-2 BP 61 EP 68 AR PII S1566-2772(00)00008-6 DI 10.1016/S1566-2772(00)00008-6 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 529EZ UT WOS:000174288200011 ER PT J AU Post, RM Weiss, SRB Leverich, GS Smith, M Zhang, LX AF Post, RM Weiss, SRB Leverich, GS Smith, M Zhang, LX TI Sensitization and kindling-like phenomena in bipolar disorder: implications for psychopharmacology SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article DE bipolar disorder; psychopharmacol; sensitization and kindling-like phenomena ID THYROTROPIN-RELEASING-HORMONE; POSTTRAUMATIC-STRESS-DISORDER; GLUCOCORTICOID-RECEPTOR FUNCTION; MESSENGER-RNA EXPRESSION; HIPPOCAMPAL VOLUME; LITHIUM-DISCONTINUATION; AFFECTIVE-ILLNESS; MATERNAL-DEPRIVATION; CONTINGENT TOLERANCE; DEPRESSED-PATIENTS AB Behavioral sensitization to psychomotor stimulants and electrophysiological kindling are two different models of learning and memory that reveal progressively increasing responsiveness to repetition of the are inducing stimulus over time. Although cocain-induced behaviors in animals and humans show many different parallels with mania and the evolution into dysphoric mania and psychosis. the development of amygdala-kindled seizures and their progression to spontaneity is obviously a highly indirect and nonhomologous model for illness progression in the affective disorders. Nonetheless, both models offer new insights into the longitudinal course and recurrence of the affective disorders and potential neurobiological mechanisms involved at the level of gene expression. A complex spatio-temporal cascade of changes in gene expression involving a host of immediate early genes (IEGs). neurotrophic factors, and late effector genes (LEGs) are postulated that reflect both primary pathological and secondary. adaptive processes whose ratio may determine the presence or absence of illness, New evidence suggests that the impact of both stressful environmental events and of antidepressants and mood stabilizers on neurotrophic factor gene expression reveals a potential basis for lasting illness-related biochemical and structural alterations in the central nervous system and their potential prevention or amelioration by therapeutic agents. Given the substantive evidence of both episode and stressor sensitization in the course of bipolar illness, the models of sensitization and kindling provide additional theoretical rationale to the growing empirical database on the importance of instituting early pharmacoprophylaxis and sustaining it for the long-term. Published by Association for Research in Nervous and Mental Disease. C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, Bldg 10,Room 35289,10 Ctr Dr MSC 1272, Bethesda, MD 20892 USA. NR 76 TC 20 Z9 21 U1 2 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD JAN PY 2001 VL 1 IS 1-2 BP 69 EP 81 AR PII S1566-2772(00)00009-8 DI 10.1016/S1566-2772(00)00009-8 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 529EZ UT WOS:000174288200012 ER PT J AU Robertson, AG Robertson, C Soutar, DS Burns, H Hole, D McCarron, P AF Robertson, AG Robertson, C Soutar, DS Burns, H Hole, D McCarron, P TI Treatment of oral cancer: The need for defined protocols and specialist centres. Variations in the treatment of oral cancer SO CLINICAL ONCOLOGY LA English DT Article DE oral cancer; radiotherapy; surgery; treatment protocols ID CLINICIAN WORKLOAD; COLORECTAL-CANCER; MANAGEMENT; SURVIVAL; RESIDUALS; HEAD; NECK AB The authors of this study aimed to identify treatment philosophies for oral cancer within the west of Scotland and to investigate any survival differences associated with the various treatment options by means of a retrospective review of case notes and cancer registry data. All patients with squamous cancer of the tongue or moor of the mouth were identified from the West of Scotland Cancer Registry for the period 1984-1990. A total of 206 patients were available for study. Five different treatment protocols were identified: 5% of patients underwent biopsy only, 16% biopsy plus radiotherapy, 11% excisional biopsy, 25% radical surgery, and 42% radical surgery plus radiotherapy. Tumour staging by the TNM classification was an important factor that determined outcome. When adjusting for T stage and nodal involvement, there was a significant effect of treatment protocol on both the disease-free period (P<0.001) and on survival (P<0.001). The treatment options were used differently by individual clinicians and were related to stage of the disease. One hundred and forty-four (70%) of the patients were treated by a single combined head and neck unit based within the plastic surgery unit at Canniesburn Hospital. The remaining 62 were treated in 13 different units throughout the west of Scotland. For those not treated in the combined head and neck unit, the increased hazard for recurrence was 1.43 (95% confidence interval (CI) 1.01-2.02), and the increased hazard ratio for death was 1.48 (95% CI 1.06-2.06) when adjusting for tumour stage, and nodal involvement. Treatment philosophies for oral cancer have a significant effect on outcome. There is a need to develop clearly defined protocols based on staging and site of disease. We believe that treatment should be carried out within a multidisciplinary setting in a combined head and neck cancer unit. C1 Western Infirm & Associated Hosp, Beatson Oncol Ctr, Glasgow G11 6NT, Lanark, Scotland. European Inst Oncol, Milan, Italy. Canniseburn Hosp, Glasgow, Lanark, Scotland. Greater Glasgow Hlth Board, Glasgow, Lanark, Scotland. Univ Glasgow, Dept Publ Hlth, Glasgow, Lanark, Scotland. NIH, Bethesda, MD 20892 USA. RP Robertson, AG (reprint author), Western Infirm & Associated Hosp, Beatson Oncol Ctr, Glasgow G11 6NT, Lanark, Scotland. NR 16 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0936-6555 J9 CLIN ONCOL-UK JI Clin. Oncol. PY 2001 VL 13 IS 6 BP 409 EP 415 DI 10.1007/s001740170003 PG 7 WC Oncology SC Oncology GA 517WG UT WOS:000173633000003 PM 11824876 ER PT J AU Katz, SI AF Katz, SI TI Dermatological research in the new millennium SO CLINICS IN DERMATOLOGY LA English DT Article C1 NIAMSD, NIH, Bethesda, MD 20892 USA. RP Katz, SI (reprint author), NIAMSD, NIH, Room 4C32,31 Ctr Dr MSC 2350, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0738-081X J9 CLIN DERMATOL JI Clin. Dermatol. PD JAN-FEB PY 2001 VL 19 IS 1 BP 51 EP 53 DI 10.1016/S0738-081X(00)00212-1 PG 3 WC Dermatology SC Dermatology GA 432GC UT WOS:000168683000013 PM 11369487 ER PT J AU Vocci, FJ Chiang, CN AF Vocci, FJ Chiang, CN TI Vaccines against nicotine - How effective are they likely to be in preventing smoking? SO CNS DRUGS LA English DT Article ID CIGARETTE-SMOKING; ACTIVE IMMUNIZATION; COCAINE ABUSE; INTRAVENOUS NICOTINE; CONJUGATE VACCINE; UNITED-STATES; BRAIN; RATS; CESSATION; DRUGS AB Cigarette smoking is the most preventable cause of death in industrialised countries. 30% of all deaths in smokers in the 35 to 69 years age range are attributed to chronic cigarette smoking; smokers dying in this age cohort lose an average of 23 years of life. Public health campaigns have attempted to reduce initiation of smoking in adolescents and to foster quitting in dependent smokers. The prevalence of smoking has declined in the US to 25% of the population, but this figure has held constant for the last decade. Vaccines against nicotine are a novel concept in the field of smoking cessation research and have not yet reached the stage of clinical testing. Vaccines could reduce smoking behaviour in 3 groups of smokers: (i) current smokers attempting to quit; (ii) former smokers wanting to avoid the possibility of relapse; and (iii) adolescent smokers before they become confirmed smokers. The rationale behind the approach is that nicotine is the pharmacological agent controlling the rate of cigarette smoking, and reducing its rate and extent of uptake into the brain may have therapeutic benefits. C1 Natl Inst Drug Abuse, Div Treatment Res & Dev, Bethesda, MD 20892 USA. RP Vocci, FJ (reprint author), Natl Inst Drug Abuse, Div Treatment Res & Dev, 6001 Execut Blvd,Room 4133,MSC 9551, Bethesda, MD 20892 USA. NR 61 TC 26 Z9 26 U1 1 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2001 VL 15 IS 7 BP 505 EP 514 DI 10.2165/00023210-200115070-00001 PG 10 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 461XT UT WOS:000170389700001 PM 11510621 ER PT J AU Gottesman, S Storz, G Rosenow, C Majdalani, N Repoila, F Wassarman, KM AF Gottesman, S Storz, G Rosenow, C Majdalani, N Repoila, F Wassarman, KM TI Small RNA regulators of translation: Mechanisms of action and approaches for identifying new small RNAs SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article ID ESCHERICHIA-COLI; RIBOSOME BINDING; COMPARATIVE GENOMICS; INTERGENIC REGIONS; RPOS; PROTEIN; GENES; DSRA; HFQ; EXPRESSION C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Affymetrix, Santa Clara, CA 95051 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA. OI Repoila, Francis/0000-0001-5149-9698; Storz, Gisela/0000-0001-6698-1241 NR 45 TC 21 Z9 22 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2001 VL 66 BP 353 EP 362 DI 10.1101/sqb.2001.66.353 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 639YQ UT WOS:000180643700036 PM 12762038 ER PT J AU Asano, K Phan, L Valasek, L Schoenfeld, LW Shalev, A Clayton, J Nielsen, K Donahue, TF Hinnebusch, AG AF Asano, K Phan, L Valasek, L Schoenfeld, LW Shalev, A Clayton, J Nielsen, K Donahue, TF Hinnebusch, AG TI A multifactor complex of eIFI, cIF2, eIF3, eIF5, and tRNA(i)(Met) promotes initiation complex assembly and couples GTP hydrolysis to AUG recognition SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article ID GUANINE-NUCLEOTIDE EXCHANGE; EUKARYOTIC TRANSLATION INITIATION-FACTOR-3; SACCHAROMYCES-CEREVISIAE; RIBOSOME BINDING; PROTEIN COMPLEX; MESSENGER-RNA; PRT1 PROTEIN; START CODON; 3 EIF3; SUBUNIT C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. RP Asano, K (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. NR 40 TC 21 Z9 23 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2001 VL 66 BP 403 EP 415 DI 10.1101/sqb.2001.66.403 PG 13 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 639YQ UT WOS:000180643700041 PM 12762043 ER PT J AU Dever, TE Roll-Mecak, A Choi, SK Lee, JH Cao, C Shin, BS Burley, SK AF Dever, TE Roll-Mecak, A Choi, SK Lee, JH Cao, C Shin, BS Burley, SK TI Universal translation initiation factor IF2/eIF5B SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article ID ELONGATION-FACTOR-G; ESCHERICHIA-COLI; FACTOR IF2; SACCHAROMYCES-CEREVISIAE; CRYSTAL-STRUCTURE; TERNARY COMPLEX; GTP HYDROLYSIS; TRANSFER-RNA; FACTOR-II; IN-VITRO C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. Rockefeller Univ, Lab Mol Biophys, New York, NY 10021 USA. RP Dever, TE (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. NR 37 TC 6 Z9 6 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2001 VL 66 BP 417 EP 424 DI 10.1101/sqb.2001.66.417 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 639YQ UT WOS:000180643700042 PM 12762044 ER PT J AU Park, E Lee, YJ AF Park, E Lee, YJ TI Estimates of standard deviation of Spearman's rank correlation coefficients with dependent observations SO COMMUNICATIONS IN STATISTICS-SIMULATION AND COMPUTATION LA English DT Article DE dependent bootstrap; stationary observation; jackknife; Monte Carlo method ID BOOTSTRAP; JACKKNIFE AB We consider the problem of estimating the standard deviation of the Fisher-transformed Spearman's rank correlation coefficient between two random variables X and Y when both or either of them is serially correlated. When X or Y is not i.i.d., Efron's bootstrap (EB) and the jackknife fail to capture the autocorrelation structure in the data. The circular block bootstrap (CBB) and the stationary bootstrap (SB) can be applied as alternative nonparametric resampling schemes for stationary time series. When we can assume a time series regression model, we can apply the parametric bootstrap (PB) and the bootstrap of residuals from the model (RB) to estimate the standard deviation. We compare these six methods-EB, the jackknife, CBB, SE, PB, and RB-of estimating the standard deviation, using the simulated data which have a highly correlated first order autoregression model. As we expect, the conventional bootstrap and the jackknife perform most poorly, and the PB and RB taking into account the time series model structure are the best in bias and mean squared errors. When estimating the standard deviation of the untransformed Spearman's rank correlation, we observe a very similar result. C1 Univ N Carolina, Dept Biostat, Chapel Hill, NC 27514 USA. NIH, Biometry & Math Stat Branch, Bethesda, MD 20892 USA. NR 14 TC 8 Z9 9 U1 1 U2 8 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0361-0918 J9 COMMUN STAT-SIMUL C JI Commun. Stat.-Simul. Comput. PY 2001 VL 30 IS 1 BP 129 EP 142 DI 10.1081/SAC-100001863 PG 14 WC Statistics & Probability SC Mathematics GA 455TQ UT WOS:000170044200012 ER PT B AU Fields, RD Eshete, F Dudek, S Ozsarac, N Stevens, B AF Fields, RD Eshete, F Dudek, S Ozsarac, N Stevens, B BE Bock, G Goode, J TI Regulation of gene expression by action potentials: dependence on complexity in cellular information processing SO COMPLEXITY IN BIOLOGICAL INFORMATION PROCESSING SE NOVARTIS FOUNDATION SYMPOSIUM LA English DT Article; Proceedings Paper CT Symposium on Complexity in Biological Information Processing CY JUL 04-06, 2000 CL BERLIN, GERMANY ID LONG-TERM POTENTIATION; ELEMENT-BINDING PROTEIN; ELECTRICAL-ACTIVITY; CREB PHOSPHORYLATION; CALCIUM OSCILLATIONS; SYNAPTIC PLASTICITY; KINETIC-ANALYSIS; NEURAL IMPULSES; CAM KINASE; CALMODULIN AB Nervous system development and plasticity are regulated by neural impulse activity, but it is not well understood how the pattern of action potential firing could regulate the expression of genes responsible for long-term adaptive responses in the nervous system. Studies on mouse sensory neurons in cell cultures equipped with stimulating electrodes show that specific genes can be regulated by different patterns of action potentials, and that the temporal dynamics of intracellular signalling cascades are critical in decoding and integrating information contained in the pattern of neural impulse activity. Functional consequences include effects on neurite outgrowth, cell adhesion, synaptic plasticity and axon-glial interactions. Signalling pathways involving Ca2+, CaM KII, MAPK and CREB are particularly important in coupling action potential firing to the transcriptional regulation of both neurons and glia, and in the conversion of short-term to long-term memory. Action potentials activate multiple convergent and divergent pathways, and the complex network properties of intracellular signalling and transcriptional regulatory mechanisms contribute to spike frequency decoding. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. OI Dudek, Serena M./0000-0003-4094-8368 NR 44 TC 26 Z9 27 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA BAFFINS LANE, CHICHESTER PO19 1UD, WEST SUSSEX, ENGLAND BN 0-471-49832-7 J9 NOVART FDN SYMP PY 2001 VL 239 BP 160 EP 176 PG 17 WC Behavioral Sciences; Medicine, General & Internal SC Behavioral Sciences; General & Internal Medicine GA BS88A UT WOS:000171312200010 PM 11529310 ER PT B AU McVeigh, E AF McVeigh, E BE Virag, N Blanc, O Kappenberger, L TI Measurement of ventricular and atrial wall motion using magnetic resonance with spin-tagging SO COMPUTER SIMULATION AND EXPERIMENTAL ASSESSMENT OF CARDIAC ELECTROPHYSIOLOGY LA English DT Proceedings Paper CT 2nd International Workshop on Computer Simulation and Experimental Assessment of Electrical Cardiac Function CY DEC 04-05, 2000 CL LAUSANNE, SWITZERLAND ID CANINE LEFT-VENTRICLE; TAGGED MR-IMAGES; MECHANICAL ACTIVATION; PACED HEART; ARRHYTHMIAS; STRETCH; STRAIN C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP McVeigh, E (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU FUTURA PUBL CO INC PI ARMONK PA 135 BEDFORD RD PO BOX 418, ARMONK, NY 10504-0418 USA BN 0-87993-492-1 PY 2001 BP 81 EP 88 PG 8 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic SC Cardiovascular System & Cardiology; Computer Science; Engineering GA BS49L UT WOS:000170086900010 ER PT B AU Lee, JS Fitzgibbon, E Butman, JA Dufresne, CR Wientroub, S Robey, PG Collins, MT AF Lee, JS Fitzgibbon, E Butman, JA Dufresne, CR Wientroub, S Robey, PG Collins, MT BE Lauritzen, CGK TI Anterior cranial base fibrous dysplasia and the effect on the optic nerve canal and vision SO CRANIOFACIAL SURGERY 9 LA English DT Proceedings Paper CT 9th International Congress of the International-Society-of-Craniofacial-Surgery CY JUN 17-20, 2001 CL VISBY, SWEDEN SP Int Soc Craniofacial Surg ID MCCUNE-ALBRIGHT SYNDROME; STIMULATORY G-PROTEIN; ACTIVATING MUTATIONS; SKULL BASE; DECOMPRESSION; BONE; GENE AB A retrospective analysis of the extent of optic nerve canal involvement with FD and its effect on vision was completed. Thirty-five patients under NIH protocol 98-D-0145 were evaluated. Involvement of the walls (0-100%), width, and height of the optic canal were digitally measured. Visual fields, acuity, colour test, and fundoscopic exams were performed. Of the 59 effected canals, the height and width were: 3.7 nun +/-0.9 and 3.4 mm +/-0.6, respectively (normal 3.0-7.0 mm). Of the involved canals, 71% had complete encasement, the remaining canals had partial encasement. All ophthalmology exams, except one, were normal. The one abnormal exam was unilateral, did not correspond to the most restricted canal, and was likely due to optic nerve traction. Thus, encasement may cause narrowing of the optic canal but does not result in vision loss. Therefore, prophylactic optic nerve decompression is not recommended based on radiographic findings since they do not correlate with vision loss. C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Lee, JS (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-1617-X PY 2001 BP 257 EP 259 PG 3 WC Surgery SC Surgery GA BU03F UT WOS:000174770400069 ER PT J AU Tsai, CJ Ma, BY Kumar, S Wolfson, H Nussinov, R AF Tsai, CJ Ma, BY Kumar, S Wolfson, H Nussinov, R TI Protein folding: Binding of conformationally fluctuating building blocks via population selection SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE dynamic landscapes; conformational ensembles; binding; folding; funnels; induced conformational change ID ON-PATHWAY INTERMEDIATE; ALPHA-LYTIC PROTEASE; MURINE DIHYDROFOLATE REDUCTASES; NATIVE ESCHERICHIA-COLI; CHAPERONIN GROEL; TRYPTOPHAN SYNTHASE; HYDROGEN-EXCHANGE; PEPTIDE-FRAGMENTS; CYTOCHROME-C; LIMITED PROTEOLYSIS AB Here we review different aspects of the protein folding literature. We present a broad range of observations, showing them to be consistent with a general hierarchical protein folding model. In such a model, local relatively stable, conformationally fluctuating building blocks bind through population selection, to yield the native state. The model includes several components: (1) the fluctuating building blocks that constitute local minima along the polypeptide chain, which even if unstable still possess higher population times than all alternate conformations; (2) the landscape around the bottom of the funnels; (3) the consideration that protein folding involves intramolecular recognition; (4) similar landscapes are observed for folding and for binding, and that (5) the landscape is dynamic, changing with the conditions. The model considers protein folding to be guided by native interactions. The reviewed literature includes the effects of changing the conditions, intermediates and kinetic traps, mutations, similar topologies, fragment complementation experiments, fragments and pathways, focusing on one specific well-studied example, that of the dihydrofolate reductase, chaperones, and chaperonines, in vivo vs. in vitro folding, still using the dihydrofolate example, amyloid formation, and molecular "disorder". These are consistent with the view that binding and folding are similar events, with the differences stemming from different stabilities and hence population times. C1 NCI, Intramural Res Support Program, SAIC, Lab Expt & Computat Biol, Ft Detrick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Fac Med, Dept Human Genet & Mol Med, Sackler Inst Mol MEd, IL-69978 Tel Aviv, Israel. RP Tsai, CJ (reprint author), NCI, Intramural Res Support Program, SAIC, Lab Expt & Computat Biol, Bldg 469,Rm 151, Ft Detrick, MD 21702 USA. RI Wolfson, Haim/A-1837-2011; Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU NCI NIH HHS [N01-CO-56000] NR 122 TC 46 Z9 47 U1 0 U2 12 PU CRC PRESS LLC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 USA SN 1040-9238 J9 CRIT REV BIOCHEM MOL JI Crit. Rev. Biochem. Mol. Biol. PY 2001 VL 36 IS 5 BP 399 EP 433 DI 10.1080/20014091074228 PG 47 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 490BJ UT WOS:000172030100001 PM 11724155 ER PT J AU Evans, M AF Evans, M TI Ripe for study: Complementary and alternative treatments for obesity SO CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION LA English DT Review C1 NIH, Div Extramural Res Training & Review, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Evans, M (reprint author), NIH, Div Extramural Res Training & Review, Natl Ctr Complementary & Alternat Med, Democracy 2,Suite 106, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU CRC PRESS LLC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 USA SN 1040-8398 J9 CRIT REV FOOD SCI JI Crit. Rev. Food Sci. Nutr. PY 2001 VL 41 IS 1 BP 35 EP 37 DI 10.1080/20014091091698 PG 3 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 390KF UT WOS:000166293700004 PM 11152044 ER PT J AU Clelland, R Graybill, DC Hubbard, V Khan, LK Stern, JS Wadden, TA Weinsier, R Yanovski, S AF Clelland, R Graybill, DC Hubbard, V Khan, LK Stern, JS Wadden, TA Weinsier, R Yanovski, S TI Commercial weight loss products and programs: What consumers stand to gain and lose - A public conference on the information consumers need to evaluate weight loss products and programs SO CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION LA English DT Review C1 Fed Trade Commiss, Div Serv Ind Practices, Washington, DC 20580 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. Univ Calif Davis, Dept Internal Med, Davis, CA 95616 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Alabama, Birmingham, AL USA. RP Clelland, R (reprint author), Fed Trade Commiss, Div Serv Ind Practices, Washington, DC 20580 USA. NR 3 TC 9 Z9 9 U1 24 U2 29 PU CRC PRESS LLC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 USA SN 1040-8398 J9 CRIT REV FOOD SCI JI Crit. Rev. Food Sci. Nutr. PY 2001 VL 41 IS 1 BP 45 EP 70 PG 26 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 390KF UT WOS:000166293700008 PM 11152047 ER PT J AU Koski, GK Lyakh, LA Cohen, PA Rice, NR AF Koski, GK Lyakh, LA Cohen, PA Rice, NR TI CD14(+) monocytes as dendritic cell precursors: Diverse maturation-inducing pathways lead to common activation of NF-kappa B/RelB SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article; Proceedings Paper CT 10th International Symposium on the Immunobiology of Proteins and Peptides CY SEP 12-16, 2000 CL TAHOE CITY, CALIFORNIA SP Allergan, Allergene, Baxter Healthcare Corp, Int Bioimmune Syst, Multiple Peptidy Syst, Wyeth Lederle Vaccines DE dendritic cell; nuclear factor-kappa B; intracellular signaling; maturation ID CHRONIC MYELOGENOUS LEUKEMIA; EPIDERMAL LANGERHANS CELLS; COLONY-STIMULATING FACTOR; ANTIGEN-PRESENTING CELLS; NECROSIS-FACTOR-ALPHA; C-KIT-LIGAND; CALCIUM IONOPHORE; BONE-MARROW; TNF-ALPHA; T-CELLS AB Dendritic cells are extremely potent antigen-presenting cells that are primarily responsible for the sensitization of naive T cells to protein antigen in vivo. For this reason, dendritic cells are the focus of intense study. Despite this interest, relatively little information is available on the signal transduction pathways that regulate the development and activity of these cells. The last several years, however, have seen a steady accumulation of data regarding methods to cultivate large numbers of DC, the characterization of attendant signals that drive DC development from various precursor cells, and the induction of nuclear transcription factors that presumably direct alterations in gene expression that regulate aspects of DC development. In this review, we briefly summarize some of these findings, with emphasis on monocyte-derived dendritic cells and a discussion of two distinct types of signaling pathways that appear to regulate the final maturation of DC: one pathway calcium-dependent and cyclosporine A-sensitive, the other pathway CsA-insensitive. Although evidence suggests these signaling pathways are quite divergent in their upstream components, they both appear to activate NF-kappaB nuclear factors, particularly RelB. C1 NCI, Ctr Canc Res, Div Basic Sci, Frederick, MD 21702 USA. Cleveland Clin Fdn, Surg Res Ctr, Cleveland, OH 44195 USA. RP Koski, GK (reprint author), Univ Penn, Dept Surg, Harrison Dept Surg Res, 3400 Spruce St, Philadelphia, PA 19104 USA. NR 58 TC 39 Z9 40 U1 0 U2 0 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2001 VL 21 IS 1-3 BP 179 EP 189 PG 11 WC Immunology SC Immunology GA 480ZM UT WOS:000171493400013 PM 11642603 ER PT J AU Childs, RW AF Childs, RW TI Nonmyeloablative blood stem cell transplantation as adoptive allogeneic immunotherapy for metastatic renal cell carcinoma SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article; Proceedings Paper CT 10th International Symposium on the Immunobiology of Proteins and Peptides CY SEP 12-16, 2000 CL TAHOE CITY, CALIFORNIA SP Allergan, Allergene, Baxter Healthcare Corp, Int Bioimmune Syst, Multiple Peptidy Syst, Wyeth Lederle Vaccines DE nonmyeloablative; NST; renal cell carcinoma; immunotherapy; allogeneic stem cell transplantation; minitransplant; graft-versus-tumor; GVT ID BONE-MARROW TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; GRAFT-VERSUS-LEUKEMIA; MYELOABLATIVE THERAPY; BREAST-CANCER; HOST DISEASE; CHIMERISM; CHEMOTHERAPY; ENGRAFTMENT; REGRESSION AB Allogeneic stem cell transplantation has emerged as a potentially curative form of immunotherapy for patients with hematological malignancies that are resistant to conventional chemo/radiotherapy. Donor T cell populations targeting allogeneic minor histocompatibility antigens expressed on the patient's malignant cells are felt to be the driving force of the graft-versus-leukemia reaction, although to date only a handful of these antigens have been fully characterized. Recent data from experimental animal models and limited clinical data in humans suggest that graft-versus-tumor effects, analogous to the graft-versus-leukemia reaction, may be generated against malignancies of epithelial origin. This article reviews the results of a pilot trial demonstrating graft-versus-renal cell carcinoma effects following nonmyeloablative stem cell transplantation, highlighting the potential of allogeneic immunotherapy for treating cancer. C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Childs, RW (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 32 TC 12 Z9 12 U1 0 U2 0 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2001 VL 21 IS 1-3 BP 191 EP 203 PG 13 WC Immunology SC Immunology GA 480ZM UT WOS:000171493400014 PM 11642604 ER PT J AU Arlen, M Tsang, A Scherrer, J Wolf, J Saric, O AF Arlen, M Tsang, A Scherrer, J Wolf, J Saric, O TI The identification and development of specific monoclonal antibodies to squamous cell carcinoma SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article; Proceedings Paper CT 10th International Symposium on the Immunobiology of Proteins and Peptides CY SEP 12-16, 2000 CL TAHOE CITY, CALIFORNIA SP Allergan, Allergene, Baxter Healthcare Corp, Int Bioimmune Syst, Multiple Peptidy Syst, Wyeth Lederle Vaccines DE chimeric antibody; squamous cell carcinoma; ADCC; immunohistochemistry; pap smear AB We have developed specific monoclonal antibodies to immunogenic glycoproteins expressed selectively, on the cell membrane of squamous cell malignancies. These proteins serve to act as tumor markers that characterize this malignancy; there has be no evidence of cross reactivity to normal epithelial cells. Analysis of patterns of expression reveals that those membrane proteins identified by monoclonals AD7 and 5C6 appear early in cellular transformation to malignancy. At such a time, immunohistochemical recognition is seen in the presence of genotypic alterations, yet phenotypic changes may not be apparent. Of additional interest is that these monoclonal antibodies exhibit strong ADCC allowing the tumor proteins to not only serve as a marker of malignancy but as a target for therapeutic destruction. C1 N Shore Univ Hosp, Dept Surg, Manhasset, NY 11030 USA. Int Bioimmune Syst, Great Neck, NY USA. NCI, Bethesda, MD 20892 USA. RP Arlen, M (reprint author), N Shore Univ Hosp, Dept Surg, Manhasset, NY 11030 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2001 VL 21 IS 1-3 BP 205 EP 214 PG 10 WC Immunology SC Immunology GA 480ZM UT WOS:000171493400015 PM 11642605 ER PT J AU Cohen, PA Peng, LM Kjaergaard, J Plautz, GE Finke, JH Koski, GK Czerniecki, BJ Shu, SY AF Cohen, PA Peng, LM Kjaergaard, J Plautz, GE Finke, JH Koski, GK Czerniecki, BJ Shu, SY TI T-cell adoptive therapy of tumors: Mechanisms of improved therapeutic performance SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article; Proceedings Paper CT 10th International Symposium on the Immunobiology of Proteins and Peptides CY SEP 12-16, 2000 CL TAHOE CITY, CALIFORNIA SP Allergan, Allergene, Baxter Healthcare Corp, Int Bioimmune Syst, Multiple Peptidy Syst, Wyeth Lederle Vaccines DE CD4(+) T cells; CD8(+) T cells; L-selectin(low) T cells; helper-independent T cells; tumoricidal macrophages; lymphokine-activated killer cells; dendritic cells; tumor rejection; cytotoxic T cells; interferon-gamma ID ACTIVATED KILLER-CELLS; LYMPH-NODE CELLS; SUPERFICIAL BLADDER-CANCER; BACILLUS-CALMETTE-GUERIN; HUMAN-BLOOD MONOCYTES; HUMAN NATURAL-KILLER; MHC CLASS-I; EPIDERMAL LANGERHANS CELLS; INFLAMMATORY BOWEL-DISEASE; NECROSIS-FACTOR-ALPHA AB The T cells of many cancer patients are naturally sensitized to tumor-associated antigens (Ag), or they can readily be sensitized with vaccine maneuvers. In melanoma patients, the adoptive transfer of such T cells can often be causally linked to the objective regression of established tumors. So far, few patients have shown sustained clinical benefit from such therapy, but preclinical mouse studies have now clearly delineated the hurdles that must be overcome to render T-cell-based antitumor therapy effective. Contrary to earlier expectations, it is now established that remarkably potent CD4(+) and CD8(+) pre-effector T cells are naturally sensitized even in mice bearing progressive, weakly immunogenic tumors. However, such T cells often display signal transduction impairments as a consequence of the tumor environment, which limit their acquisition of optimal effector function. Extracorporealization and culture of these tumor-sensitized T cells with appropriate activation stimuli not only restores normal signal transduction, but also confers resolute effector activity that can often sustain tumor rejection upon reinfusion. In mouse studies, the L-selectin(low) fraction of T cells in tumor-draining lymph nodes (TDLN) constitutes the potent pre-effector population and comprises both CD4(+) and helper-independent CD8(+) T cells. Appropriate in vitro activation confers an apparently unrestricted trafficking capacity to this fraction, and even the ability to proliferate within the tumor bed, leading to unprecedented tumor rejection at anatomic sites (e.g., subcutaneous and intracranial) that were historically refractory to such treatment. Such results underscore the surprising capacity of appropriately activated effector T cells to withstand the immunosuppressive, tolerogenic, and apoptotic influences of the typical tumor environment. Given the increasingly appreciated and critical communications between T cells and host Ag-presenting cells (APC), which cross-present tumor Ag, it is likely that dendritic cell-based vaccine maneuvers that promote sensitization of T1-committed L-selectin(low) antitumor T cells will play an increasingly important role in adoptive therapy strategies. C1 Cleveland Clin Fdn, Surg Res Ctr, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. Univ Penn, Med Ctr, Dept Surg, Philadelphia, PA 19104 USA. RP Cohen, PA (reprint author), Cleveland Clin Fdn, Surg Res Ctr, FF-50,9500 Euclid Ave, Cleveland, OH 44195 USA. NR 281 TC 41 Z9 48 U1 0 U2 3 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2001 VL 21 IS 1-3 BP 215 EP 248 PG 34 WC Immunology SC Immunology GA 480ZM UT WOS:000171493400016 PM 11642606 ER PT J AU Patel, V Leethanakul, C Gutkind, JS AF Patel, V Leethanakul, C Gutkind, JS TI New approaches to the understanding of the molecular basis of oral cancer SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Review DE genetic alterations; gene expression; CGAP; genomics; proteomics ID SQUAMOUS-CELL CARCINOMA; LASER-CAPTURE MICRODISSECTION; TUMOR-SUPPRESSOR GENE; POLYPOSIS-COLI GENE; NECK-CANCER; ADENOMATOUS POLYPOSIS; ALLELIC LOSS; FIELD CANCERIZATION; HEAD; EXPRESSION AB Cancers of the oral cavity, salivary glands, larynx, and pharynx, collectively referred to as squamous cell carcinomas of the head and neck (HNSCC), are the sixth most common cancer among men in the developed world. The prognosis of HNSCC patients is still poor, which reflects the fact that although the risk factors for HNSCC are well-recognized, very little is known about the molecular mechanisms responsible for this malignancy. This review describes some of the current efforts and technological advances that have focused on the creation of a complete information infrastructure for genes expressed during squamous cell carcinogenesis. These include: the recently described HNSCC-specific chromosomal alterations (cCAP); the Head and Neck Cancer Genome Anatomy Project (HN-CGAP), whose goal is the systematic identification and cataloguing of known and novel genes expressed during tumor development; and the use of laser-capture microdissection (LCM), which is pivotal for the comprehensive molecular characterization of normal, pre-cancerous, and malignant cells by means of DNA-array technology. The latter provides the means for the analysis of expression patterns of thousands of genes simultaneously. The use of LCM for proteomics and DNA analysis is also included in this review. These revolutionary approaches are likely to have an unprecedented impact on cancer biology, and provide exciting opportunities to unravel the still-unknown mechanisms involved in squamous cell carcinogenesis. They are also expected to provide a molecular blueprint for HNSCC, thus helping to identify suitable markers for the early detection of pre-neoplastic lesions, as well as novel targets for pharmacological intervention in this disease. C1 NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), NIDCR, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Room 212, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 62 TC 49 Z9 51 U1 0 U2 6 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PY 2001 VL 12 IS 1 BP 55 EP 63 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 556DA UT WOS:000175833000005 PM 11349962 ER PT J AU Dionne, RA Berthold, CW AF Dionne, RA Berthold, CW TI Therapeutic uses of non-steroidal anti-inflammatory drugs in dentistry SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Review DE NSAIDs; acute pain; chronic pain; edema; preventive analgesia ID POSTOPERATIVE DENTAL PAIN; IBUPROFEN-CODEINE COMBINATION; 3RD MOLAR SURGERY; IMMUNOREACTIVE BETA-ENDORPHIN; ACETAMINOPHEN PLUS CODEINE; ANTI-INFLAMMATORY DRUG; ANALGESIC EFFICACY; ORAL-SURGERY; DOUBLE-BLIND; NAPROXEN SODIUM AB The non-steroidal anti-inflammatory drugs (NSATDs) are among the most widely used classes of drugs for the management of acute and chronic pain in dentistry. Their therapeutic efficacy and toxicity are well-documented and provide evidence that NSAIDs generally provide an acceptable therapeutic ratio of pain relief with fewer adverse effects than the opioid-mild analgesic combination drugs that they have largely replaced for most dental applications. The great many studies done with the oral surgery model of acute pain indicate that a single dose of an NSAID is more effective than combinations of aspirin or acetaminophen plus an opioid, with fewer side-effects, thus making it preferable for ambulatory patients. The combination of an NSAID with an opioid generally results in marginal analgesic activity but with an increased incidence of side-effects, which limits its use to patients in whom the NSAID alone results in inadequate analgesia. The selective COX-2 inhibitors hold promise for clinical efficacy with less toxicity from chronic administration and may prove advantageous for the relief of chronic orofacial pain. The use of repeated doses of NSAIDs for chronic orofacial pain should be re-evaluated in light of a lack of documented efficacy and the potential for serious gastrointestinal and renal toxicity with repeated dosing. C1 Natl Inst Dent & Craniofacial Res, Pain & Neurosurg Mech Branch, NIH, Bethesda, MD 20892 USA. RP Dionne, RA (reprint author), Natl Inst Dent & Craniofacial Res, Pain & Neurosurg Mech Branch, NIH, 10 Ctr Dr,Room 1N-117, Bethesda, MD 20892 USA. EM rdionne@dir.nidcr.nih.gov NR 127 TC 40 Z9 45 U1 1 U2 7 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PY 2001 VL 12 IS 4 BP 315 EP 330 PG 16 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 556DD UT WOS:000175833300004 PM 11603504 ER PT J AU Greig, NH Utsuki, T Yu, QS Zhu, XX Holloway, HW Perry, T Lee, B Ingram, DK Lahiri, DK AF Greig, NH Utsuki, T Yu, QS Zhu, XX Holloway, HW Perry, T Lee, B Ingram, DK Lahiri, DK TI A new therapeutic target in Alzheimer's disease treatment: Attention to butyrylcholinesterase SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE Alzheimer's disease; butyrylcholinesterase; acetylcholinesterase; inhibition; amyloid; cognition; cholinergic ID MOLECULAR-FORMS; AMYLOID PLAQUES; SENILE DEMENTIA; IN-VIVO; ACETYLCHOLINESTERASE; CHOLINESTERASES; BRAIN; NEUROTRANSMITTERS; INHIBITORS; PHENSERINE AB Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly, characterised by widespread loss of central cholinergic function. The only symptomatic treatment proven effective to date is the use of cholinesterase (ChE) inhibitors to augment surviving cholinergic activity. ChE inhibitors act on the enzymes that hydrolyse acetylcholine (ACh) following synaptic release. In the healthy brain, acetylcholinesterase (AChE) predominates (80%) and butyrylcholinesterase (BuChE) is considered to play a minor role in regulating brain ACh levels. In the AD brain, BuChE activity rises while AChE activity remains unchanged or declines. Therefore both enzymes are likely to have involvement in regulating ACh levels and represent legitimate therapeutic targets to ameliorate the cholinergic deficit. The two enzymes differ in location, substrate specificity and kinetics, Recent evidence suggests that BuChE may also have a role in the aetiology and progression of AD beyond regulation of synaptic ACh levels. Experimental evidence from the use of agents with enhanced selectivity for BuChE (cymserine, MF-8622) and ChE inhibitors such as rivastigmine, which have a dual inhibitory action on both AChE and BuChE, indicate potential therapeutic benefits of inhibiting both AChE and BuChE in AD and related dementias, The development of specific BuChE inhibitors and the continued use of ChE inhibitors with the ability to inhibit BuChE in addition to AChE should lead to improved clinical outcomes. C1 NIA, Baltimore, MD 21224 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. RP Greig, NH (reprint author), NIA, Baltimore, MD 21224 USA. NR 44 TC 98 Z9 99 U1 2 U2 8 PU LIBRAPHARM PI NEWBURY PA C/O DR. PETER L CLARKE, GEMINI HOUSE, 162 CRAVEN RD, NEWBURY RG14 5NR, BERKSHIRE, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PY 2001 VL 17 IS 3 BP 159 EP 165 PG 7 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 504LL UT WOS:000172858100002 PM 11900310 ER PT J AU Salazar-Fontana, LI Bierer, BE AF Salazar-Fontana, LI Bierer, BE TI T-lymphocyte coactivator molecules SO CURRENT OPINION IN HEMATOLOGY LA English DT Article ID NECROSIS-FACTOR RECEPTOR; B-CELL ACTIVATION; OX40 LIGAND; CD40 LIGAND; COSTIMULATORY MOLECULES; CHEMOKINE RECEPTOR; DENDRITIC CELLS; CO-STIMULATION; 4-1BB LIGAND; CUTTING EDGE AB T-cell recognition and activation occurs within a specialized area of contact known as the immunologic synapse, localized to areas of glycolipid-enriched membrane microdomains. Within this area, T-cell activation is dependent not only upon specific recognition of peptide antigen embedded within molecules of the major histocompatibility complex, but also on a variety of costimulatory receptors and interactions. Engagement of T-cell receptor (TCR) with antigen alone will induce T-cell unresponsiveness; ligation of the coreceptor CD28 will prevent the induction of unresponsiveness. Novel costimulatory molecules belonging to both the CD28 and TNF/TNFR superfamilies have recently been identified. These receptors appear to act at different stages of T-cell differentiation and activation, have been shown to play a role in promoting different T-cell effector functions, and are important for B-cell differentiation and function. (C) 2001 Lippincott Williams & Wilkins, Inc. C1 NHLBI, Lab Lymphocyte Biol, NIH, Bethesda, MD 20892 USA. RP Bierer, BE (reprint author), NHLBI, Lab Lymphocyte Biol, NIH, 10 Ctr Dr,Room 10-6C208, Bethesda, MD 20892 USA. NR 58 TC 13 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JAN PY 2001 VL 8 IS 1 BP 5 EP 11 DI 10.1097/00062752-200101000-00002 PG 7 WC Hematology SC Hematology GA 465FW UT WOS:000170579800002 PM 11138627 ER PT J AU Hostetter, TH Rosenberg, ME Ibrahim, HN Juknevicius, I AF Hostetter, TH Rosenberg, ME Ibrahim, HN Juknevicius, I TI Aldosterone in renal disease SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review ID CONVERTING ENZYME-INHIBITION; REMNANT KIDNEY MODEL; GLOMERULAR INJURY; ANGIOTENSIN-II; RAT; HYPERTENSION; NEPHROPATHY; MASS; MICROCIRCULATION; EXPRESSION AB Blockade of the renin-angiotensin-aldosterone system has proved effective in retarding the progression of renal disease in the remnant kidney model, as well as other experimental diseases, and most importantly, in a range of progressive human renal diseases. Attention has focused on the role of angiotensin II in propagating progression both by its hemodynamic and non-hemodynamic actions. Recent evidence, predominantly in the remnant kidney model, indicates that the drugs used to block this hormone system, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, also lower aldosterone levels. Aldosterone as well as angiotensin II thus appears to be instrumental in sustaining the hypertension and fibroproliferative destruction of the residual kidney. Curr Opin Nephrol Hypertens 10:105-110. (C) 2001 Lippincott Williams & Wilkins. C1 Univ Minnesota, Div Renal Dis Hypertens, Minneapolis, MN 55455 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Hostetter, TH (reprint author), Univ Minnesota, Div Renal Dis Hypertens, 516 Delaware St SE, Minneapolis, MN 55455 USA. NR 58 TC 35 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD JAN PY 2001 VL 10 IS 1 BP 105 EP 110 DI 10.1097/00041552-200101000-00016 PG 6 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 388NA UT WOS:000166186100016 PM 11195042 ER PT J AU Fenton, WS AF Fenton, WS TI Comorbid conditions in schizophrenia SO CURRENT OPINION IN PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; SCHIZOAFFECTIVE DISORDER; TRIGLYCERIDE LEVELS; SUICIDAL-BEHAVIOR; WEIGHT-GAIN; OLANZAPINE; SYMPTOMS; CLOZAPINE; ELEVATION AB Psychiatric syndromes, including depression, obsessive-compulsive disorder, panic, and substance use disorders, co-occur with schizophrenia at significant rates, These syndromes interact with schizophrenia symptoms in clinically meaningful ways, and can be associated with adverse outcomes such as suicide, long-term disability, medication nonadherence, and frequent hospitalization. Data to inform treatment of cooccurring syndromes are largely anecdotal, and further studies are required to understand better the risks and benefits of treatment options. Weight gain and disturbances of glucose and lipid metabolism are emerging as significant medical comorbidities in patients treated with new-generation antipsychotic agents, and preventive interventions are urgently needed. Curl Opin Psychiatry 14:17-23. (C) 2001 Lippincott Williams & Wilkins. C1 NIMH, Div Mental Disorders Behav Res & AIDS, Bethesda, MD 20892 USA. RP Fenton, WS (reprint author), NIMH, Div Mental Disorders Behav Res & AIDS, 6001 Execut Blvd,MSC 9621, Bethesda, MD 20892 USA. NR 48 TC 28 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD JAN PY 2001 VL 14 IS 1 BP 17 EP 23 DI 10.1097/00001504-200101000-00004 PG 7 WC Psychiatry SC Psychiatry GA 389XZ UT WOS:000166265100004 ER PT J AU Tomac, AC Hoffer, BJ AF Tomac, AC Hoffer, BJ TI Assignment of the mouse Park2(PARKIN), the homologue to a new human Parkinson candidate gene, to the telomeric region of mouse 17A3.2-3.3, by in situ hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article C1 NIDA, NIH, Baltimore, MD 21224 USA. RP Hoffer, BJ (reprint author), NIDA, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2001 VL 95 IS 1-2 BP 120 EP 121 DI 10.1159/000057032 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 549AJ UT WOS:000175422100025 PM 11978985 ER PT J AU Nash, WG Menninger, JC Wienberg, J Padilla-Nash, HM O'Brien, SJ AF Nash, WG Menninger, JC Wienberg, J Padilla-Nash, HM O'Brien, SJ TI The pattern of phylogenomic evolution of the Canidae SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID CHROMOSOME-BANDING PATTERNS; BLUE FOX; CARNIVORE KARYOTYPE; SILVER FOX; RED FOX; DOG; INTERRELATIONSHIPS; URSIDAE; FAMILY; FELIDS AB Canidae species fall into two categories with respect to their chromosome composition: these with high numbered largely acrocentric karyotypes and others with a low numbered principally metacentric karyotype. Those species with low numbered metacentric karyotypes are derived from multiple independent fusions of chromosome segments found as acrocentric chromosomes in the high numbered species, Extensive chromosome homology is apparent among acrocentric chromosome arms within Canidae species; however, little chromosome arm homology exists between Canidae species and those from other Carnivore families. Here we use Zoo-FISH (fluorescent in situ hybridization, also called chromosomal painting) probes from flow-sorted chromosomes of the Japanese raccoon dog (Nyctereutes procyonoides) to examine two phylogenetically divergent canids, the arctic fox (Alopex lagopus) and the crab-eating fox (Cerdocyon thous). The results affirm intra-canid chromosome homologies, also implicated by G-banding. In addition, painting probes from domestic cat (Felis catus), representative of the ancestral carnivore karyotype (ACK), and giant panda (Ailuropoda melanoleuca) were used to define primitive homologous segments apparent between canids and other carnivore families. Canid chromosomes seem unique among carnivores in that many canid chromosome arms are mosaics of two to four homology segments of the ACK chromosome arms. The mosaic pattern apparently preceded the divergence of modem canid species since conserved homology segments among different canid species are common, even though those segments are rearranged relative to the ancestral carnivore genome arrangement. The results indicate an ancestral episode of extensive centric fission leading to an ancestral canid genome organization that was subsequently reorganized by multiple chromosome fusion events in some but not all Canidae lineages. Copyright (C) 2002 S. Karger AG, Basel. C1 NCI, Lab Genom Divers, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. H&W Cytogenet Serv Inc, Lovettsville, VA USA. NCI, Intramural Res Support Program, SAIC, Frederick, MD 21701 USA. NCI, Basic Res Lab, Frederick, MD USA. NCI, Ctr Canc Res, Genet Branch, Bethesda, MD USA. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 27 TC 51 Z9 53 U1 1 U2 29 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2001 VL 95 IS 3-4 BP 210 EP 224 DI 10.1159/000059348 PG 15 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 566CB UT WOS:000176408300015 PM 12063402 ER PT J AU Annilo, T Tammur, J Hutchinson, A Rzhetsky, A Dean, M Allikmets, R AF Annilo, T Tammur, J Hutchinson, A Rzhetsky, A Dean, M Allikmets, R TI Human and mouse orthologs of a new ATP-binding cassette gene, ABCG4 SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID MULTIDRUG-RESISTANCE; TRANSPORT; CHOLESTEROL; PROTEINS; ALIGNMENT; CELLS AB We characterized a new ATP-binding cassette (ABC) transporter gene from human and mouse that is highly expressed in the brain. The gene, ABCG4, produces several transcripts that differ at the 5' end and encode proteins of various lengths. The ABCG4 protein is closely related to the Drosophila white and human ABCG1 genes, and belongs to the ABCG subfamily several members of which are involved in cholesterol transport. All representatives of this "reverse transporter" subfamily, including ABCG4, have a single ATP-binding domain at the N-terminus and a single C-terminal set of transmembrane segments. ABCG4 maps to human chromosome 11q23, between the markers D11S939 and D11S924, and Abcg4 to a conserved syntenic region on mouse chromosome 9. The abundant expression of this gene in the brain and close evolutionary relationship to the other members of the subfamily suggests a potential role for ABCG4 in cholesterol transport processes in this tissue. Copyright (C) 2002 S. Karger AG, Basel. C1 Columbia Univ, Dept Ophthalmol, Eye Res Addit, New York, NY 10032 USA. Columbia Univ, Dept Pathol, New York, NY 10032 USA. Columbia Univ, Dept Med Informat, New York, NY 10032 USA. Columbia Univ, Columbia Genome Ctr, New York, NY 10032 USA. NCI, FCRDC, Lab Genom Divers, Frederick, MD USA. Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, EE-50090 Tartu, Estonia. RP Allikmets, R (reprint author), Columbia Univ, Dept Ophthalmol, Eye Res Addit, Rm 715,630 W 168th St, New York, NY 10032 USA. RI rzhetsky, andrey/B-6118-2012; Dean, Michael/G-8172-2012; Annilo, Tarmo/J-2900-2013 OI Dean, Michael/0000-0003-2234-0631; Annilo, Tarmo/0000-0002-9588-3058 FU NEI NIH HHS [EY-13435] NR 19 TC 28 Z9 32 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2001 VL 94 IS 3-4 BP 196 EP 201 DI 10.1159/000048816 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 526YA UT WOS:000174156400018 PM 11856881 ER PT J AU Neusser, M Stanyon, R Bigoni, F Wienberg, J Muller, S AF Neusser, M Stanyon, R Bigoni, F Wienberg, J Muller, S TI Molecular cytotaxonomy of New World monkeys (Platyrrhini) - comparative analysis of five species by multi-color chromosome painting gives evidence for a classification of Callimico goeldii within the family of Callitrichidae SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID IN-SITU HYBRIDIZATION; DNA-SEQUENCES; PRIMATES; SYSTEMATICS; HOMOLOGIES; FISH; REARRANGEMENTS; FLUORESCENCE; EVOLUTION; HUMANS AB Chromosome rearrangements are considered as "rare genomic changes" and can provide useful markers and even landmarks for reconstructing phylogenies complementary to DNA sequence data and bio-morphological comparisons. Here, we applied multi-directional chromosome painting to reconstruct the chromosome phylogeny and evolutionary relationships among the New World monkey (Platyrrhini) species Callithrix argentata, Cebuella pygmaea, Saguinus oedipus, Callithrix jacchus and Callimico goeldii. The results clarified several aspects of New Wold monkey phylogeny. In particular the phylogenetic position of C goeldii was elucidated, which has been controversially discussed and variously classified in the family Callitrichidae, in the family Cebidae or in its own family Callimiconidae. Comparative genome maps were established by multi-color fluorescence in situ hybridization (FISH) with human, S. oedipus and Lagothrix lagothricha chromosome-specific DNA probes. From these data we reconstructed the putative ancestral karyotype of all Callitrichidae. Various derived chromosomal syntenies are shared by all five species and cytogenetically define Callitrichidae - including Callimico goeldii - as a distinctive group within the Platyrrhini. C pygmaea and C. argentata share identical chromosomal syntenies from which S. oedipus and C, jacchus differ by single independent translocations. A common derived chromosomal change links Callimico with the marmosets to the exclusion of the tamarins, however, it has further diverged from an ancestral marmoset karyotype by at least four apomorphic rearrangements. Saimiri. sciureus, representing the Cebinae, exclusively shares a derived syntenic association with all Callithrichidae, defining the genus Saimiri as a sister group. Copyright (C) 2002 S. Karger AG, Basel. C1 Univ Munich, Inst Anthropol & Human Genet, D-80333 Munich, Germany. Natl Canc Inst, Basic Res Lab, Frederick, MD USA. RP Muller, S (reprint author), Univ Munich, Inst Anthropol & Human Genet, Richard Wagner Str 10, D-80333 Munich, Germany. OI Stanyon, Roscoe/0000-0002-7229-1092 NR 48 TC 59 Z9 60 U1 1 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2001 VL 94 IS 3-4 BP 206 EP 215 DI 10.1159/000048818 PG 10 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 526YA UT WOS:000174156400020 PM 11856883 ER PT J AU Cui, Q Matsusue, K Toh, Y Kono, A Takiguchi, S AF Cui, Q Matsusue, K Toh, Y Kono, A Takiguchi, S TI Assignment of the metastasis-associated gene (Mta1) to mouse chromosome band 12F and the metastasis-associated gene 2 (Mta2) to mouse chromosome band 19B by fluorescence in situ hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID HISTONE DEACETYLASE; INSITU HYBRIDIZATION; COMPLEX; OVEREXPRESSION; EXPRESSION; CARCINOMAS; CHROMATIN; CLONING C1 Kyushu Natl Canc Ctr, Clin Res Inst, Div Chemotherapy, Minami Ku, Fukuoka 8111395, Japan. Kyushu Natl Canc Ctr, Dept Surg Gastroenterol, Fukuoka 8111395, Japan. TRANSGEN INC, Kumamoto, Japan. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Takiguchi, S (reprint author), Kyushu Natl Canc Ctr, Clin Res Inst, Div Chemotherapy, Minami Ku, 3-1-1 Notame, Fukuoka 8111395, Japan. NR 12 TC 1 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2001 VL 94 IS 3-4 BP 246 EP 247 DI 10.1159/000048825 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 526YA UT WOS:000174156400027 PM 11856890 ER PT J AU Leach, R Duniec-Dmuchowski, Z Tanaka, T Ko, MS Krawetz, SA AF Leach, R Duniec-Dmuchowski, Z Tanaka, T Ko, MS Krawetz, SA TI Assignment of OVCOV1 (alias CGI-15) to human chromosome 20 band q13.1 -> q13.2 by fluorescent in situ hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID INSITU HYBRIDIZATION; GENES C1 Wayne State Univ, Sch Med, CS Mott Ctr Human Growth & Dev, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Leach, R (reprint author), Wayne State Univ, Sch Med, CS Mott Ctr Human Growth & Dev, Dept Obstet & Gynecol, 275 E Hancock, Detroit, MI 48201 USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 FU NICHD NIH HHS [HD36512, HD98004] NR 4 TC 2 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2001 VL 94 IS 3-4 BP 252 EP 253 DI 10.1159/000048828 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 526YA UT WOS:000174156400030 PM 11856893 ER PT J AU Zimonjic, DB Zhang, H Shan, Z Factor, V Trent, J Thorgeirsson, SS Popescu, NC AF Zimonjic, DB Zhang, H Shan, Z Factor, V Trent, J Thorgeirsson, SS Popescu, NC TI DNA amplification associated with double minutes originating from chromosome 19 in mouse hepatocellular carcinoma SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID GROWTH-FACTOR-ALPHA; GENE AMPLIFICATION; TRANSGENIC MICE; C-MYC; SEQUENCE AMPLIFICATION; CRYPTIC SITES; CANCER; MICRODISSECTION; PROTEINS; CELLS AB DNA amplification is associated with genomic instability, the main characteristic of cancer cells, and it frequently involves protooncogenes. Double minute chromosomes (DM) and homogeneously stained regions (HSR) are cytological manifestations of DNA amplification. Gain of chromosome 19 is a recurrent alteration in mouse hepatocellular carcinoma (HCC). In one tumor cell line established from HCC developed in myc transgenic mice. DM derived from chromosome 19 were identified by spectral karyotyping and confirmed by fluorescence in situ hybridization (FISH). A probe generated by PCR from microdissected DM was localized by FISH on normal and HCC-derived cell lines on DM and chromosome 19 at two sites separated by several medium size G-bands. This organization of DM containing amplified sequences from separate loci of the same chromosome, indicates a complex mechanism of DNA amplification. possibly involving more than one gene. DM or HSR were not previously identified in mouse HCC and adult human HCC. The recognition of these loci could lead to the cloning of new genes or identification of known genes important in development or progression of HCC. Copyright (C) 2001 S. Karger AG, Basel. C1 NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NHGRI, Canc Genet Lab, NIH, Bethesda, MD 20892 USA. RP Popescu, NC (reprint author), NCI, Expt Carcinogenesis Lab, NIH, 37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. NR 26 TC 14 Z9 14 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2001 VL 93 IS 1-2 BP 114 EP 116 DI 10.1159/000056961 PG 3 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 457XU UT WOS:000170163600025 PM 11474192 ER PT J AU Galdzicki, Z Huang, W Siarey, R Balbo, A Rapoport, SI AF Galdzicki, Z Huang, W Siarey, R Balbo, A Rapoport, SI TI Abnormal synaptic plasticity and elevated brain, myo-inositol levels in Ts65dn mice, a model of Down syndrome SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract ID MYOINOSITOL; MOUSE C1 Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. SUNY Stony Brook, Dept Radiol, Stony Brook, NY 11794 USA. NIH, NIA, SBPM, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2001 VL 92 IS 1-2 BP 11 EP 11 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 422LU UT WOS:000168120400020 ER PT J AU Carpten, JD AF Carpten, JD CA Prostate Invest Grp TI A detailed map of the 1q24 -> q31 region: The next step, sequence analysis SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2001 VL 92 IS 1-2 BP 43 EP 43 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 422LU UT WOS:000168120400066 ER PT J AU Caldwell, GM Eddy, RL Day, CD Haley, LH Cooper, PR Sait, SSJ Hejtmancik, F Smith, RJH Morton, CC Higgins, MJ Shows, TB AF Caldwell, GM Eddy, RL Day, CD Haley, LH Cooper, PR Sait, SSJ Hejtmancik, F Smith, RJH Morton, CC Higgins, MJ Shows, TB TI Mapping of genes and transcribed sequences in a gene rich 400-kb region on human chromosome 11p15.1 -> p14 SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID SULFONYLUREA RECEPTOR GENE; FAMILIAL HYPERINSULINISM; HYBRIDIZATION; MUTATIONS; DOMAINS; 1C AB We have identified a number of transcribed sequences within a 400-kb interval on chromosome 11p15.1 --> p14. Six genes and 13 novel transcripts including ESTs, cDNAs and exons have been identified and assigned to this region. Comparison of mRNA sequence with genomic sequence has enabled us to determine the exon/intron structure of four of the genes (NUCB2, PIK3C2A, RPS13 and OR7E14P). Copyright (C) 2001 S. Karger AG, Basel. C1 New York State Dept Hlth, Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. New York State Dept Hlth, Roswell Pk Canc Inst, Dept Cytogenet, Buffalo, NY 14263 USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Iowa Hosp & Clin, Dept Otolaryngol, Iowa City, IA 52242 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Shows, TB (reprint author), New York State Dept Hlth, Roswell Pk Canc Inst, Dept Canc Genet, Elm & Carlton St, Buffalo, NY 14263 USA. FU NIDCD NIH HHS [DC03697] NR 21 TC 1 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2001 VL 92 IS 1-2 BP 103 EP 107 DI 10.1159/000056877 PG 5 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 422LU UT WOS:000168120400095 PM 11306805 ER PT J AU Shulenin, S Schriml, LM Remaley, AT Fojo, S Brewer, B Allikmets, R Dean, M AF Shulenin, S Schriml, LM Remaley, AT Fojo, S Brewer, B Allikmets, R Dean, M TI An ATP-binding cassette gene (ABCG5) from the ABCG (White) gene subfamily maps to human chromosome 2p21 in the region of the Sitosterolemia locus SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID TANGIER-DISEASE; DIETARY-CHOLESTEROL; TRANSPORTER-1; MUTATIONS; LIVER AB We characterized a new human ATP-binding cassette (ABC) transporter gene that is highly expressed in the liver. The gene, ABCG5, contains 13 exons and encodes a 651 amino acid protein. The predicted protein is closely related to the Drosophila white gene and a human gene, ABCG1, which is induced by cholesterol. This subfamily of genes all have a single ATP-binding domain at the N-terminus and a single C-terminal set of transmembrane segments. ABCG5 maps to human chromosome 2p21, between the markers D2S117 and D2S119. The abundant expression of this gene in the liver suggests that the protein product has an important role in transport of specific molecule(s) into or out of this tissue. Copyright (C) 2001 S. Karger AG, Basel. C1 NCI Frederick, Lab Genom Divers, Frederick, MD 21702 USA. NHLBI, Bethesda, MD 20892 USA. Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA. Columbia Univ, Dept Pathol, New York, NY 10027 USA. RP Dean, M (reprint author), NCI Frederick, Lab Genom Divers, Bldg 560,Rm 21-18, Frederick, MD 21702 USA. RI Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; Schriml, Lynn/0000-0001-8910-9851 NR 17 TC 17 Z9 17 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2001 VL 92 IS 3-4 BP 204 EP 208 DI 10.1159/000056903 PG 5 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 450HG UT WOS:000169735500006 PM 11435688 ER PT J AU Broccardo, C Osorio, J Luciani, MF Schriml, LM Prades, C Shulenin, S Arnould, I Naudin, L Lafargue, C Rosier, M Jordan, B Mattei, M Dean, M Denefle, P Chimini, G AF Broccardo, C Osorio, J Luciani, MF Schriml, LM Prades, C Shulenin, S Arnould, I Naudin, L Lafargue, C Rosier, M Jordan, B Mattei, M Dean, M Denefle, P Chimini, G TI Comparative analysis of the promoter structure and genomic organization of the human and mouse ABCA7 gene encoding a novel ABCA transporter SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID ATP-BINDING CASSETTE; DENSITY-LIPOPROTEIN DEFICIENCY; TANGIER-DISEASE; STARGARDT-DISEASE; IDENTIFICATION; MUTATIONS; MICE; CHOLESTEROL; SEQUENCE AB We report here the genomic and transcriptional characterization in mouse and man of a novel transporter of the ABCA subclass, named ABCA7. As it is the case for other ABCA genes, the predicted protein encoded by ABCA7 is a full symmetric transporter, highly conserved across species. The ABCA7 gene maps to human chromosome 19 and to the homologous region at band B4-C1 on mouse chromosome 10. The preferential expression of ABCA7 in the spleen, thymus, and fetal liver is consistent with the finding, in both human and mouse promoter, of sites targeted by lymphomyeloid-specific transcription factors. This suggests that ABCA7 may play a pivotal role in the developmental specification of hematopoietic cell lineages. Copyright (C) 2001 S. Karger AG, Basel. C1 Ctr Immunol Marseille Luminy, CNRS, INSERM, F-13288 Marseille 09, France. Aventis Pharma, Evry Genom Ctr, Evry, France. NCI, Ctr Genome Divers, NIH, Frederick, MD 21701 USA. INSERM, UD00, F-13258 Marseille, France. RP Chimini, G (reprint author), Ctr Immunol Marseille Luminy, CNRS, INSERM, Parc Sci Luminy,Case 906, F-13288 Marseille 09, France. RI Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; Schriml, Lynn/0000-0001-8910-9851 NR 28 TC 26 Z9 29 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2001 VL 92 IS 3-4 BP 264 EP 270 DI 10.1159/000056914 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 450HG UT WOS:000169735500017 PM 11435699 ER PT J AU Liang, SX Jenkins, NA Gilbert, DJ Copeland, NG Phillips, WD AF Liang, SX Jenkins, NA Gilbert, DJ Copeland, NG Phillips, WD TI Structure and chromosome location of the mouse P2X(1) purinoceptor gene (P2rx1) SO CYTOGENETICS AND CELL GENETICS LA English DT Article; Proceedings Paper CT 14th European Colloquium on Cytogenetics of Domestic Animals CY JUN 27-30, 2000 CL UNIV VET & PHARMACEUT SCI, BRNO, CZECH REPUBLIC SP Univ Vet & Pharmaceut Sci, Vet Res Inst, Fac Vet Med, Acad Sci Czech Republic, Biol Soc, Cytogenet Sect, J G Mendel Museum HO UNIV VET & PHARMACEUT SCI ID GATED ION CHANNELS; P-2X RECEPTOR; ATP RECEPTOR; VAS-DEFERENS; LOCALIZATION; CLONING; TRANSMISSION; EXPRESSION; CDNA AB P2X(1) receptors are ATP-gated cation channels that mediate the fast, purinergic component of sympathetic nerve-smooth muscle neurotransmission in the mouse vas deferens and may serve comparable functions in the urinary bladder and the arteries. The gene for mouse P2X(1) (P2rx(1)) was cloned and its genomic structure defined by sequencing The gene spans about 10 kb and consists of 12 exons. All splice sites conformed to the GT-AG motif and the exon-intron boundaries were largely conserved with other members of the P2X gene family so far cloned. A single transcription-starting site was identified by 5' RACE analysis, 233 bp upstream of the translation start site. The P2X(1) gene maps to the central region of mouse chromosome 11. Copyright (C) 2001 S. Karger AG, Basel. C1 Univ Sydney, Inst Biomed Res, Dept Physiol, Sydney, NSW 2006, Australia. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Phillips, WD (reprint author), Univ Sydney, Inst Biomed Res, Dept Physiol, Sydney, NSW 2006, Australia. NR 21 TC 5 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2001 VL 92 IS 3-4 BP 333 EP 336 DI 10.1159/000056923 PG 4 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 450HG UT WOS:000169735500026 PM 11435708 ER PT J AU Cho, MS Yee, H Brown, C Jeang, KT Chan, S AF Cho, MS Yee, H Brown, C Jeang, KT Chan, S TI An oriP expression vector containing the HIV-1 Tat/TAR transactivation axis produces high levels of protein expression in mammalian cells SO CYTOTECHNOLOGY LA English DT Article DE HKB11 cells; IL-2 mutein; mammalian cell expression; oriP; Tat/TAR ID HUMAN IMMUNODEFICIENCY VIRUS; TRANS-ACTIVATION; GENE-EXPRESSION; NUCLEAR-PROTEIN; ELEMENT AB A mammalian gene expression vector based on cytomegalovirus (CMV) enhancer/promoter (CMVe/p) for the regulation of gene expression was further optimized by adding oriP elements derived from Epstein-Barr virus (EBV) and the Tat/TAR transactivation axis from human immunodeficiency virus type 1 (HIV-1). Using the Tat/TAR-oriP expression vector, a transient transfection system was optimized for an extended culture period to produce large amounts of secreted IL-2SA (an IL-2 mutein) in HKB11 cells. We observed a 4-fold increase in IL-2SA expression in cells transfected with vectors containing the HIV-1 transactivation axis (Tat/TAR) or oriP elements alone when compared to cells transfected with the control vector having a CMVe/p. Cells transfected with expression vectors equipped with both oriP and Tat/TAR showed an 18-fold increase in IL-2SA expression. This transient transfection system maintained high secretion of IL-2SA for a period of 10-day with no appreciable loss in expression. We demonstrate that during this 10-day culture period, it was possible to produce 1-100 mg of proteins using 500 mug of plasmid DNA. C1 Bayer Corp, Mol & Cell Biol Proc Sci Biotechnol, Berkeley, CA USA. NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Cho, MS (reprint author), Bayer Corp, Mol & Cell Biol Proc Sci Biotechnol, Berkeley, CA USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 17 TC 10 Z9 10 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-9069 J9 CYTOTECHNOLOGY JI Cytotechnology PY 2001 VL 37 IS 1 BP 23 EP 30 DI 10.1023/A:1016124911071 PG 8 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA 572FA UT WOS:000176761700003 PM 19002911 ER PT J AU Valle, MA Kester, MB Burns, AL Marx, SJ Spiegel, AM Shiloach, J AF Valle, MA Kester, MB Burns, AL Marx, SJ Spiegel, AM Shiloach, J TI Production and purification of human menin from Drosophila melanogaster S2 cells using stirred tank reactor SO CYTOTECHNOLOGY LA English DT Article DE Drosophila Schneider; menin ID SCHNEIDER-2 CELLS; EXPRESSION; PLASMINOGEN; GENE AB A process was developed for producing human menin from transformed Drosophila Schneider 2 cells. Protein expression was achieved after inducing the metallothionein promoter by adding copper sulfate to cells growing in suspension in a stirred-tank reactor. Experiments in shake flasks showed that the production of menin was improved when the induction was conducted late in the exponential phase of cell growth at a concentration of 1-2 x 10(7) cells ml(-1), with a copper concentration of 0.2 mM for no more than 24 h. This observation was confirmed by experiments in bench-scale fermentors. Subsequently, a pilot-scale fermentation yielded 1 mg l(-1) culture of purified menin. C1 NIDDK, Biotechnol Unit, NIH, Bethesda, MD 20892 USA. Univ Maryland, Agr Biotechnol Ctr, College Pk, MD 20742 USA. NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Shiloach, J (reprint author), NIDDK, Biotechnol Unit, NIH, Bethesda, MD 20892 USA. NR 16 TC 9 Z9 10 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-9069 J9 CYTOTECHNOLOGY JI Cytotechnology PY 2001 VL 35 IS 2 BP 127 EP 135 DI 10.1023/A:1017586523710 PG 9 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA 471UW UT WOS:000170947900005 PM 19003289 ER PT J AU Wong, ECC Maher, VE Hines, K Lee, J Carter, CS Goletz, T Kopp, W Mackall, CL Berzofsky, JA Read, EJ AF Wong, ECC Maher, VE Hines, K Lee, J Carter, CS Goletz, T Kopp, W Mackall, CL Berzofsky, JA Read, EJ TI Development of a clinical-scale method for generation of dendritic cells from PBMC for use in cancer immunotherapy SO CYTOTHERAPY LA English DT Article DE dendritic cells (DCs); peripheral blood monocytes; immunotherapy ID BLOOD MONOCYTES; SERUM; ANTIGEN; MATURE AB Background There is growing interest bt the use of dendritic cells (DCs) for treatment of malignancy and infectious disease Our goal was to develop a clinical-scale method to prepare autologous DCs for cancer clinical trials Methods PBMC were collected from normal donors or cancer patients by automated leukapheresis, purified by counterflow centrifugal elutriation and placed into culture in polystyrene flasks at 1 X 10(6) cells/mL for 5-7 days at 37 degreesC, with 5% CO2, with IL-4 and GM-CSF. Conditions investigated included media formulation, supplementation with heat-inactivated allogeneic AB serum or autologous plasma and time to harvest (Day 5 or Day 7). DCs were evaluated for morphology, quantitative yield viability phenotype and function, including mixed leukocyte response and recall response to tetanus toroid and influenza virus. Results DCs with a typical immature phenotype (CD14-negative, CD1a-positive, mannose receptor-positive, CD80-positive, CD83-negntive) were generated most consistently in RPMI 1640 supplemented with 10% allogeneic AB serum or 10% autologous plasma. Cell yield was higher at Day 5 than Day 7, without detectable differences in phenotype or function. In pediatric sarcoma patients autologous DCs bad enhanced function compared with monocytes from which they were generated. In this patient group, starting with 8.0 +/- 3.7 x 10(8 fr)esh or cryopreserved autologous monocytes, DC yield was 2.1 +/- 1.0 x 10(8) cells, or 29% of the starting monocyte number: Discussion In the optimized clinical-scale method, purified peripheral monocytes are cultured for 5 days in flasks at 1 X 10(6) cells/mL in RPMI 1640, 10% allogeneic AB serum or autologous plasma, IL-4 and CM-CSF: This method avoids the use of FBS and results in in immature DCs suitable for clinical trials. C1 NCI, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD USA. SAIC, Frederick, MD USA. RP Read, EJ (reprint author), NCI, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, NIH, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-56000] NR 19 TC 35 Z9 35 U1 0 U2 2 PU ISIS MEDICAL MEDIA LTD PI OXFORD PA 59 ST ALDATES, OXFORD OX1 1ST, ENGLAND SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2001 VL 3 IS 1 BP 19 EP 29 DI 10.1080/146532401753156377 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 433CB UT WOS:000168736800004 PM 12028840 ER PT J AU Gallego, MI Binart, N Robinson, GW Okagaki, R Coschigano, KT Perry, J Kopchick, JJ Oka, T Kelly, PA Hennighausen, L AF Gallego, MI Binart, N Robinson, GW Okagaki, R Coschigano, KT Perry, J Kopchick, JJ Oka, T Kelly, PA Hennighausen, L TI Prolactin, growth hormone, and epidermal growth factor activate stat5 in different compartments of mammary tissue and exert different and overlapping developmental effects SO DEVELOPMENTAL BIOLOGY LA English DT Article ID GLAND DEVELOPMENT; EGF RECEPTOR; FACTOR-I; TYROSINE PHOSPHORYLATION; DUCTAL MORPHOGENESIS; TARGETED DISRUPTION; EPITHELIAL-CELLS; GENE-EXPRESSION; MOUSE; MICE AB Prolactin (Prl)-induced phosphorylation of Stat (signal transducer and activator of transcription) 5 is considered a key event in functional mammary development and differentiation. We now demonstrate that not only Prl, but also growth hormone (GH) and epidermal growth factor (EGF), can activate Stat5 in mammary tissue. We investigated the roles of these hormones in mammary development using mice in which the respective receptors had been inactivated. Although Prl receptor (PrlR)-null mice are infertile, we were able to maintain pregnancies in a few mice by treatment with progesterone. Mammary tissue in these mice was severely underdeveloped and exhibited limited differentiation as assessed by the phosphorylation status of Stat5 and the expression of milk protein genes. PrlR +/- mice showed impaired mammary development and alveolar differentiation during pregnancy, which corresponded with reduced phosphorylation levels of Stat5a and 5b, and impaired expression of milk protein genes. Development of the glands in these mice was arrested at around day 13 of pregnancy. While Prl activated Stat5 only in the epithelium, GH and EGF activated Stat5 preferentially in the stroma. To assess the relevance of the GH receptor (GHR) in the mammary gland, we transplanted GHR-null epithelium into cleared fat pads of wild-type mice. These experiments demonstrated that the GHR in the epithelium is not required for functional mammary development. Similarly, the EGFR in the epithelium is not required for alveolar development. In contrast, epithelial PrlR is required for mammary development and milk protein gene expression during pregnancy. Although GH is not required for alveolar development, we were able to demonstrate its lactogenic function in cultured mammary epithelium from PrlR-null mice. However, ductal development in GHR-null mice was impaired, supporting the notion that GH signals through the stromal compartment. Our findings demonstrate that GH, Prl, and EGF activate Stat5 in separate compartments, which in turn reflects their specific roles in ductal and alveolar development and differentiation. C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. Fac Med Necker Enfants Malad, INSERM, U344, Unite Endocrinol Mol, F-75730 Paris, France. Ohio Univ, Coll Osteopath Med, Dept Biomed Sci, Athens, OH 45701 USA. Ohio Univ, Coll Osteopath Med, Edison Biotechnol Inst, Athens, OH 45701 USA. RP Gallego, MI (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RI Kelly, Paul/A-7951-2008; Robinson, Gertraud/I-2136-2012 NR 46 TC 143 Z9 145 U1 3 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE 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 JAN 1 PY 2001 VL 229 IS 1 BP 163 EP 175 DI 10.1006/dbio.2000.9961 PG 13 WC Developmental Biology SC Developmental Biology GA 390ZK UT WOS:000166329500012 PM 11133161 ER PT J AU Mohamed, OA Bustin, M Clarke, HJ AF Mohamed, OA Bustin, M Clarke, HJ TI High-mobility group proteins 14 and 17 maintain the timing of early embryonic development in the mouse SO DEVELOPMENTAL BIOLOGY LA English DT Article DE chromatin; high-mobility group proteins; mouse; embryogenesis; cell cycle ID ZYGOTIC GENE ACTIVATION; RNA-POLYMERASE-II; CHROMOSOMAL-PROTEINS; DNA-REPLICATION; MAMMALIAN DEVELOPMENT; CELL-CYCLE; TRANSCRIPTIONAL ACTIVITY; ENHANCER FUNCTION; CHROMATIN; EXPRESSION AB The high-mobility group (HMG) proteins 14 and 17 are abundant chromosomal proteins that bind to nucleosomes and enhance transcription. We report that both mRNA species and both proteins are present throughout oogenesis and preimplantation development of the mouse. When antisense oligonudeotides targeting each mRNA species are injected into one-cell embryos, the proteins become depleted at the two- and four-cell stages and reaccumulate at the eight-cell stage. One-cell embryos injected with antisense oligonucleotides targeting both HMG-14 and HMG-17 cleave to the two-cell stage. Subsequent cleavages, however, are delayed compared with control-injected embryos. Nevertheless, these embryos ultimately reach the blastocyst stage. Similarly, injection into the nuclei of two-cell embryos of a peptide corresponding to the common nucleosome-binding domain of HMG-14 and HMG-17 delays progression to the four-cell stage. Furthermore, both RNA and protein synthesis is transiently reduced in antisense-injected embryos compared with injected controls. These results identify HMG-14 and HMG-17 as constitutive components of mouse oocyte and embryonic chromatin and establish a link between the structure of embryonic chromatin and the normal progression of embryonic development. (C) 2001 Academic Press. C1 McGill Univ, Dept Obstet & Gynecol, Montreal, PQ H3A 1A1, Canada. McGill Univ, Dept Biol, Montreal, PQ H3A 1A1, Canada. NCI, Prot Sect, Mol Carcinogenesis Lab, Div Basic Sci,NIH, Bethesda, MD 20892 USA. RP Mohamed, OA (reprint author), McGill Univ, Dept Obstet & Gynecol, Montreal, PQ H3A 1A1, Canada. RI Bustin, Michael/G-6155-2015 NR 62 TC 31 Z9 35 U1 0 U2 0 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 JAN 1 PY 2001 VL 229 IS 1 BP 237 EP 249 DI 10.1006/dbio.2000.9942 PG 13 WC Developmental Biology SC Developmental Biology GA 390ZK UT WOS:000166329500018 PM 11133167 ER PT J AU Tidhar, A Reichenstein, M Cohen, D Faerman, A Copeland, NG Gilbert, DJ Jenkins, NA Shani, M AF Tidhar, A Reichenstein, M Cohen, D Faerman, A Copeland, NG Gilbert, DJ Jenkins, NA Shani, M TI A novel transgenic marker for migrating limb muscle precursors and for vascular smooth muscle cells SO DEVELOPMENTAL DYNAMICS LA English DT Article DE transgenic mice; insertional mutagenesis; limb muscles; cell migration; vascular smooth muscle; pericytes; neointima ID INSERTIONAL MUTAGENESIS; CHICK-EMBRYOS; MOUSE; EXPRESSION; MICE; GENE; DIFFERENTIATION; MUSCULATURE; ARTERIAL; DISEASE AB A unique pattern of LacZ expression was found in a transgenic mouse line, likely due to regulatory elements at the site of integration. Two new genes flanking the transgene were identified. At early stages of development, the transgene is transiently expressed in ventro-lateral demomyotomal cells migrating from the somites into the limb buds. At late developmental stages and in the adult, lacZ staining marks vascular smooth muscle cells throughout the vascular bed, with the exception of the major elastic arteries, and in pericytes. No expression was detected in skeletal and smooth muscles. Different patterns of expression in vascular smooth muscles was observed at distinct levels of the vascular tree, in arteries as well as in veins. Vessel injury, resulting in stimulation of smooth muscle cells proliferation and migration, is associated with transgene down-regulation. After the formation of neointima thickening, it is reactivated. This transgenic insertion may therefore be used as a useful marker to identify novel physiological cues or genetic elements involved in the regulation of the vascular smooth muscle phenotype(s). It may also provide an experimental, tool for studying vasculature and the involvement of pericytes in regulating microvascular homeostasis. (C) 2001 Wiley-Liss, Inc. C1 Agr Res Org, Volcani Ctr, Inst Anim Sci, IL-50250 Bet Dagan, Israel. NCI, Mouse Canc Genet Program, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Shani, M (reprint author), Agr Res Org, Volcani Ctr, Inst Anim Sci, IL-50250 Bet Dagan, Israel. NR 66 TC 47 Z9 50 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 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JAN PY 2001 VL 220 IS 1 BP 60 EP 73 DI 10.1002/1097-0177(2000)9999:9999<::AID-DVDY1089>3.0.CO;2-X PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 385MN UT WOS:000166008400006 PM 11146508 ER PT J AU Westergaard, GC Lussier, ID Higley, JD AF Westergaard, GC Lussier, ID Higley, JD TI Familial influences on hand preference: Genotypic variation between closely related primate species SO DEVELOPMENTAL NEUROPSYCHOLOGY LA English DT Article ID CEREBRAL LATERALIZATION; BIOLOGICAL MECHANISMS; FUNCTIONAL ASYMMETRY; HUMAN HANDEDNESS; RHESUS-MONKEYS; MACACA-MULATTA; ASSOCIATIONS; HYPOTHESIS; HEMISPHERE; PATHOLOGY AB The emergence of hemispheric specialization has important implications for the development of higher order cognitive processes, including language and spatial skills. In this research we sought to further understand psychobiological processes associated with the development of hemispheric specialization by examining and comparing familial influences on hand preference in two closely related macaque species: rhesus macaques (Macaca mulatta) and pigtailed macaques (Macaca nemestrina). The results of our study indicate contrasting patterns of familial influence on hand preference in each species. For the rhesus macaque we found a positive correlation in the direction of hand preference between mothers and their juvenile offspring, and for the pigtailed macaque we found a negative mother-offspring correlation in the direction of hand preference. Fathers did not contribute significantly to the direction of hand preference in either species. There was a trend toward a positive correlation for strength and consistency of hand preference between parents and offspring in rhesus macaques but not in pigtailed macaques. These findings indicate that maternal influences on offspring hand preference vary between closely related primate species and lead us to question the generalizability of universal single-factor theories used to explain intergenerational transmission of hand preference in humans. C1 LABS Virginia Inc, Div Res & Dev, Yemassee, SC 29945 USA. NIAAA, Lab Clin Studies, Rockville, MD 20852 USA. RP Westergaard, GC (reprint author), LABS Virginia Inc, Div Res, 95 Castle Hall Rd,POB 557, Yemassee, SC 29945 USA. FU NCRR NIH HHS [5U42RR05083, R24 RR09983] NR 44 TC 5 Z9 5 U1 0 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 8756-5641 J9 DEV NEUROPSYCHOL JI Dev. Neuropsychol. PY 2001 VL 20 IS 3 BP 605 EP 617 DI 10.1207/875656401753549825 PG 13 WC Psychology, Developmental; Psychology; Psychology, Experimental SC Psychology GA 540LM UT WOS:000174930500004 PM 12002096 ER PT J AU Monk, CS Webb, SJ Nelson, CA AF Monk, CS Webb, SJ Nelson, CA TI Prenatal neurobiological development: Molecular mechanisms and anatomical change SO DEVELOPMENTAL NEUROPSYCHOLOGY LA English DT Review ID DEVELOPING CEREBRAL-CORTEX; HUMAN PREFRONTAL CORTEX; FETAL MONKEY NEOCORTEX; PROGRAMMED CELL-DEATH; GROWTH CONE GUIDANCE; NEURONAL MIGRATION; NERVOUS-SYSTEM; RHESUS-MONKEY; OCULAR DOMINANCE; NEURAL INDUCTION AB During prenatal development, the central nervous system is transformed from a thin layer of unspecified tissue into a complex system that can process information and organize actions. There are 8 general mechanisms that permit this transformation: neural induction, neurulation, proliferation, migration, axonal outgrowth, synaptogenesis, differentiation, and apoptosis. These processes as well as the anatomical changes they cause are described. Future research with humans, such as in utero MRI as well as behavioral and electrophysiological testing of infants following specific prenatal perturbations, is suggested to link the findings from molecular approaches to developmental neuropsychology. C1 Univ Minnesota, Inst Child Dev, Dept Pediat, Minneapolis, MN 55455 USA. RP Monk, CS (reprint author), NIMH, Sect Dev & Affect Neurosci, Bldg 1,B3-10, Bethesda, MD 20892 USA. RI Monk, Christopher/J-1805-2014 FU NICHD NIH HHS [HD01751]; NIMH NIH HHS [MH12132]; NINDS NIH HHS [NS32976] NR 117 TC 36 Z9 37 U1 1 U2 3 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 8756-5641 J9 DEV NEUROPSYCHOL JI Dev. Neuropsychol. PY 2001 VL 19 IS 2 BP 211 EP 236 DI 10.1207/S15326942DN1902_5 PG 26 WC Psychology, Developmental; Psychology; Psychology, Experimental SC Psychology GA 465YH UT WOS:000170617200005 PM 11530976 ER PT J AU Hahn, CS DiPietro, JA AF Hahn, CS DiPietro, JA TI In vitro fertilization and the family: Quality of parenting, family functioning, and child psychosocial adjustment SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID ASSISTED REPRODUCTION FAMILIES; REARING ATTITUDES; STRESS INDEX; HONG-KONG; MOTHERS; CHINESE; BEHAVIOR; QUESTIONNAIRE; TECHNOLOGY; AMERICAN AB This study examined associations between homologous in vitro fertilization (IVF) and quality of parenting, family functioning, and emotional and behavioral adjustment of 3-7-year-old children. A cross-sectional survey was conducted in Taiwan with 54 IVF mother-child pairs and 59 mother-child pairs with children conceived naturally. IVF mothers reported a greater level of protectiveness toward their children than control mothers. Teachers, blind to condition. rated IVF mothers as displaying greater warmth but not overprotective or intrusive parenting behaviors toward their children. Teachers scored children of IVF as having fewer behavioral problems than control children. In contrast, NF mothers reported less satisfaction with aspects of family functioning. Family composition moderated parenting stress: IVF mothers with only 1 child perceived less parenting stress than did those in the control group. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Populat & Family Hlth Sci, Baltimore, MD 21218 USA. RP Hahn, CS (reprint author), NICHHD, Child & Family Res Sect, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. FU PHS HHS [MCJ-000106] NR 70 TC 51 Z9 57 U1 0 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD JAN PY 2001 VL 37 IS 1 BP 37 EP 48 DI 10.1037//0012-1649.37.1.37 PG 12 WC Psychology, Developmental SC Psychology GA 394RW UT WOS:000166537900004 PM 11206432 ER PT J AU Marrero, DG Peyrot, M Garfield, S AF Marrero, DG Peyrot, M Garfield, S TI Promoting behavioral science research in diabetes SO DIABETES CARE LA English DT Editorial Material C1 Natl Inst Fitness & Sport, Indianapolis, IN 46202 USA. Loyola Coll, Baltimore, MD 21210 USA. NIDDKD, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. RP Marrero, DG (reprint author), Natl Inst Fitness & Sport, NIFS-IF122,250 Univ Blvd, Indianapolis, IN 46202 USA. NR 2 TC 7 Z9 8 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2001 VL 24 IS 1 BP 1 EP 2 DI 10.2337/diacare.24.1.1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 386XX UT WOS:000166091600001 PM 11194211 ER PT J AU Weyer, C Tataranni, PA Bogardus, C Pratley, RE AF Weyer, C Tataranni, PA Bogardus, C Pratley, RE TI Insulin resistance and insulin secretory dysfunction are independent predictors of worsening of glucose tolerance during each stage of type a diabetes development SO DIABETES CARE LA English DT Article ID PIMA-INDIANS; MELLITUS; SENSITIVITY; INDIVIDUALS; DEFICIENCY; MODEL AB OBJECTIVE - Although prospective studies indicate that insulin resistance and insulin secretory dysfunction predict type 2 diabetes, they provide limited information on the relative contributions of both abnormalities to worsening glucose tolerance at different developmental stages of the disease. We therefore assessed the predictive effect of insulin resistance and insulin secretory dysfunction separately for the progression from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) and from IGT to diabetes. RESEARCH DESIGN AND METHODS - Insulin-stimulated glucose disposal (M) (hyperinsulinemic clamp), acute insulin secretory response (AIR) (25-g intravenous glucose tolerance test), and body composition (hydrodensitometry or dual-energy X-ray absorptiometry) were measured in 254 Pima Indians with NGT and in 145 Pima Indians with IGT, who were then followed for 0.5-13 years. RESULTS - After follow-ups of 4.4 +/- 3.1 and 5.5 +/- 3.4 years, 79 (31%) of the subjects with initial NGT had developed IGT, and 64 (44%) of the subjects with initial IGT had developed diabetes. In proportional-hazards analyses with adjustment for age, sex, and percent body fat, low M and low AIR were independent predictors of both the progression from NGT to IGT (relative hazards [95% CI] for 10th vs. 90th percentile: M 2.4 [1.2-4.7], P < 0.02; AIR 2.1 [1.1-4.1], P < 0.04) and from IGT to diabetes (M 2.5 [1.3-5.0], P < 0.01;AIR 1.8 [0.99-3.3], P = 0.055). CONCLUSIONS - During each stage of the development of type 2 diabetes, insulin resistance and insulin secretory dysfunction are independent predictors of worsening glucose tolerance and are, therefore, both targets for the primary prevention of the disease. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. RP Weyer, C (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St,Rm 5-41, Phoenix, AZ 85016 USA. NR 20 TC 201 Z9 225 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2001 VL 24 IS 1 BP 89 EP 94 DI 10.2337/diacare.24.1.89 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 386XX UT WOS:000166091600018 PM 11194248 ER PT J AU Cai, T Krause, MW Odenwald, WF Toyama, R Notkins, AL AF Cai, T Krause, MW Odenwald, WF Toyama, R Notkins, AL TI The IA-2 gene family: homologs in Caenorhabditis elegans, Drosophila and zebrafish SO DIABETOLOGIA LA English DT Article DE C. elegans; Drosophila; zebrafish; IA-2; insulin-dependent diabetes mellitus ID PROTEIN-TYROSINE-PHOSPHATASE; DEPENDENT DIABETES-MELLITUS; MOLECULAR-CLONING; TRANSMEMBRANE PROTEIN; AUTOANTIGEN; EXPRESSION; IA-2-BETA; AUTOANTIBODIES; SEQUENCE; 37-KDA AB Aims/hypothesis. IA-2 and IA-2 beta are major autoantigens in Type I (insulin-dependent) diabetes mellitus and are expressed in neuroendocrine tissues including the brain and pancreatic islets of Langerhans. Based on sequence analysis, IA-2 and IA-2 beta are transmembrane protein tyrosine phosphatases but lack phosphatase activity because of critical amino acid substitutions in the catalytic domain. We studied the evolutionary conservation of IA-2 and IA-2 beta genes and searched for homologs in non-mammalian vertebrates and invertebrates. Methods. IA-2 from various species was identified from EST sequences or cloned from cDNA libraries or both. Expression in tissues was determined by transfection and in situ hybridization. Results. We identified homologs of IA-2 in C, elegans, Drosophila, and zebrafish which showed 46, 58 and 82% identity and 60, 65 and 87 % similarity, respectively, to the amino acids of the intracellular domain of human IA-2. Further studies showed that IA-2 was expressed in the neural tissues of the three species. Comparison of the genomic structure of the intracellular domain of human IA-2 with that of human IA-2 beta showed that they were nearly identical and comparison of the intron-exon boundaries of Drosophila IA-2 with human IA-2 and IA-2 beta showed a high degree of relatedness. Conclusion/Interpretation. Based on these findings and sequence analysis of IA-2 homologs in mammals, we conclude that there is an IA-2 gene family which is a part of the larger protein tyrosine phosphatase superfamily. The IA-2 and IA-2 beta genes represent two distinct subgroups within the IA-2 family which originated over 500 million years ago, long before the development of the pancreatic islets of Langerhans. C1 Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Sect Dev Biol, Mol Biol Lab, NIH, Bethesda, MD USA. Natl Inst Neurol Disorders & Stroke, Neurogenet Unit, Neurochem Lab, NIH, Bethesda, MD USA. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Notkins, AL (reprint author), Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bldg 30,Room 121,30 Convent Dr,MSC 4322, Bethesda, MD 20892 USA. OI Krause, Michael/0000-0001-6127-3940 NR 25 TC 31 Z9 32 U1 1 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2001 VL 44 IS 1 BP 81 EP 88 DI 10.1007/s001250051583 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 394EG UT WOS:000166510700012 PM 11206415 ER PT J AU Lewis, L AF Lewis, L TI The role of mental health patient organizations in disease management - Focus on the US National Depressive and Manic-Depressive Association SO DISEASE MANAGEMENT & HEALTH OUTCOMES LA English DT Article AB Mood disorders are serious chronic illnesses that are the leading cause of disability worldwide. Up to two-thirds of all people with a mood disorder are undiagnosed. In the US, there are three suicides for every two homicides, with 70% of these deaths attributed to untreated depression. Mental health advocacy organizations play an important role in the management of these disorders by urging those who are undiagnosed or untreated to seek treatment. Stigma is the number one barrier to mental healthcare, according to the US Surgeon General. Advocacy groups work to eliminate the stigma surrounding mental illness in order to encourage more people to seek treatment. They have a role in disease management as they enhance communication between patients and healthcare providers, an area in which studies have shown a significant gap in perceptions. Advocacy groups educate people so that they can play an active role in their own treatment plans. It has been demonstrated that participation in patient support groups increases patient compliance with treatment plans and decreases incidences of hospitalization for the illnesses. A critical role in disease management is patient advocacy for improved access to care, so that those needing treatment can actually receive it. Finally, mental heath advocacy groups have a role in managing the disease through 'grassroots' efforts to promote expanded research for better treatments, and eventually cures, for mental illnesses. C1 Natl Depress & Man Depress Assoc, Chicago, IL 60610 USA. NIH, Council Publ Representat, Bethesda, MD 20892 USA. NIMH, Bethesda, MD 20892 USA. RP Lewis, L (reprint author), Natl Depress & Man Depress Assoc, 730 N Franklin, Chicago, IL 60610 USA. NR 11 TC 3 Z9 3 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1173-8790 J9 DIS MANAG HEALTH OUT JI Dis. Manag. Health Outcomes PY 2001 VL 9 IS 11 BP 607 EP 617 DI 10.2165/00115677-200109110-00001 PG 11 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 494YZ UT WOS:000172314600001 ER PT J AU Kutkat, L Srivastava, S AF Kutkat, L Srivastava, S TI Introduction - The Early Detection Research Network: A platform for communication and collaboration SO DISEASE MARKERS LA English DT Editorial Material C1 Natl Canc Inst, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Rockville, MD 20852 USA. RP Srivastava, S (reprint author), Natl Canc Inst, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, 6130 Execut Blvd,Suite 330F, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2001 VL 17 IS 1 BP 3 EP 4 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 433EY UT WOS:000168747300001 ER PT J AU Strausberg, RL AF Strausberg, RL TI Talkin' omics SO DISEASE MARKERS LA English DT Editorial Material C1 NCI, Canc Genom Off, Bethesda, MD 20892 USA. RP Strausberg, RL (reprint author), NCI, Canc Genom Off, 31 Ctr Dr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2001 VL 17 IS 2 BP 39 EP 39 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 491LG UT WOS:000172109400001 ER PT J AU Herrmann, PC Liotta, LA Petricoin, EF AF Herrmann, PC Liotta, LA Petricoin, EF TI Cancer proteomics: The state of the art SO DISEASE MARKERS LA English DT Article DE proteomics; laser capture microdissection; cancer; signal transduction ID LASER CAPTURE MICRODISSECTION; MASS-SPECTROMETRY; 2-DIMENSIONAL ELECTROPHORESIS; DIFFERENTIAL EXPRESSION; TAILORED THERAPY; CELL CARCINOMA; IN-VITRO; PROTEIN; IDENTIFICATION; TISSUE AB Now that the human genome has been determined, the field of proteomics is ramping up to tackle the vast protein networks that both control and are controlled by the information encoded by the genome. The study of proteomics should yield an unparalleled understanding of cancer as well as an invaluable new target for therapeutic intervention and markers for early detection. This rapidly expanding field attempts to track the protein interactions responsible for all cellular processes. By careful analysis of these systems, a detailed understanding of the molecular causes and consequences of cancer should emerge. A brief overview of some of the cutting edge technologies employed by this rapidly expanding field is given, along with specific examples of how these technologies are employed. Soon cellular protein networks will be understood at a level that will permit a totally new paradigm of diagnosis and will allow therapy tailored to individual patients and situations. C1 US FDA, Tissue Proteom Unit, Div Therapeut Prod, Ctr Biol Evaluat Res,Clin Proteom Program, Bethesda, MD 20892 USA. NCI, Pathol Lab, Clin Prote Program, NIH, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), US FDA, Tissue Proteom Unit, Div Therapeut Prod, Ctr Biol Evaluat Res,Clin Proteom Program, Bldg 29A,Room 2B02,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 50 TC 41 Z9 44 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2001 VL 17 IS 2 BP 49 EP 57 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 491LG UT WOS:000172109400003 PM 11673651 ER PT J AU Chen, YD Yakhini, Z Ben-Dor, A Dougherty, E Trent, JM Bittner, M AF Chen, YD Yakhini, Z Ben-Dor, A Dougherty, E Trent, JM Bittner, M TI Analysis of expression patterns: The scope of the problem, the problem of scope SO DISEASE MARKERS LA English DT Article ID GENE-EXPRESSION; MOLECULAR CLASSIFICATION; HYBRIDIZATION; MICROARRAY AB Studies of the expression patterns of many genes simultaneously lead to the observation that even in closely related pathologies, there are numerous genes that are differentially expressed in consistent patterns correlated to each sample type. The early uses of the enabling technology, microarrays, was focused on gathering mechanistic biological insights. The early findings now pose another clear challenge, finding ways to effectively use this kind of information to develop diagnostics. C1 NHGRI, Canc Genet Branch, NIH, Rockville, MD 20850 USA. Agilent Labs, Chem & Biol Syst Dept, Palo Alto, CA 94304 USA. Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA. RP Bittner, M (reprint author), NHGRI, Canc Genet Branch, NIH, Bldg 49,Room 4A52,9000 Rockville Pike, Rockville, MD 20850 USA. NR 22 TC 6 Z9 6 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2001 VL 17 IS 2 BP 59 EP 65 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 491LG UT WOS:000172109400004 PM 11673652 ER PT J AU Weinstein, JN AF Weinstein, JN TI Searching for pharmacogenomic markers: The synergy between omic and hypothesis-driven research SO DISEASE MARKERS LA English DT Article DE microarray; genomics; proteomics; omics; cancer; cell line; pharmacology; pharmacogenomics; molecular marker; cancer therapy; clustered image map; MedMiner ID NATIONAL-CANCER-INSTITUTE; TUMOR-CELL-LINES; DIFFERENTIAL CYTOTOXICITY DATA; ANTICANCER DRUG SCREEN; MOLECULAR PHARMACOLOGY; CLUSTER-ANALYSIS; EXPRESSION PATTERNS; ELLIPTICINE ANALOGS; DISCOVERY; DATABASE AB With 35,000 genes and hundreds of thousands of protein states to identify, correlate, and understand, it no longer suffices to rely on studies of one gene, gene product, or process at a time. We have entered the "omic" era in biology. But large-scale omic studies of cellular molecules in aggregate rarely can answer interesting questions without the assistance of information from traditional hypothesis-driven research. The two types of science are synergistic. A case in point is the set of pharmacogenomic studies that we and our collaborators have done with the 60 human cancer cell lines of the National Cancer Institute's drug discovery program. Those cells (the NCI-60) have been characterized pharmacologically with respect to their sensitivity to > 70, 000 chemical compounds. We are further characterizing them at the DNA, RNA, protein, and functional levels. Our major aim is to identify pharmacogenomic markers that can aid in drug discovery and design, as well as in individualization of cancer therapy. The bioinformatic and chemoinformatic challenges of this study have demanded novel methods for analysis and visualization of high-dimensional data. Included are the color-coded "clustered image map" and also the MedMiner program package, which captures and organizes the biomedical literature on gene-gene and gene-drug relationships. Microarray transcript expression studies of the 60 cell lines reveal, for example, a gene-drug correlation with potential clinical implications - that between the asparagine synthetase gene and the enzyme-drug L-asparaginase in ovarian cancer cells. C1 NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Weinstein, JN (reprint author), NIH, Bldg 37,Rm 4E-28,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Weinstein@dtpax2.ncifcrf.gov NR 42 TC 10 Z9 11 U1 3 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2001 VL 17 IS 2 BP 77 EP 88 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 491LG UT WOS:000172109400006 PM 11673654 ER PT J AU Chanock, S AF Chanock, S TI Candidate genes and single nucleotide polymorphisms (SNPs) in the study of human disease SO DISEASE MARKERS LA English DT Article DE variation; genome; genetic; mutation; disease susceptibility ID BLADDER-CANCER RISK; POOLED DNA SAMPLES; FAMILIAL ALZHEIMER-DISEASE; LINKAGE DISEQUILIBRIUM; HUMAN-GENOME; BETA(2)-ADRENERGIC RECEPTOR; PROMOTER POLYMORPHISM; HIV-1 INFECTION; REGULAR USE; ALLELE AB The genomic revolution has generated an extraordinary resource, the catalog of variation within the human genome, for investigating biological, evolutionary and medical questions. Together with new, more efficient platforms for high-throughput genotyping, it is possible to begin to dissect genetic contributions to complex trait diseases, specifically examining common variants, such as the single nucleotide polymorphism (SNP). At the same time, these tools will make it possible to identify determinants of disease with the expectation of eventually, tailoring therapies based upon specific profiles. However, a number of methodological, practical and ethical issues must be addressed before the analysis of genetic variation becomes a standard of clinical medicine. The currents of variation in human biology are reviewed here, with a specific emphasis on future challenges and directions. C1 NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Gaithersburg, MD 20877 USA. RP Chanock, S (reprint author), NCI, Pediat Oncol Branch, Immunocompromised Host Sect, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. EM sc83a@nih.gov NR 55 TC 52 Z9 58 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2001 VL 17 IS 2 BP 89 EP 98 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 491LG UT WOS:000172109400007 PM 11673655 ER PT J AU Srivastava, M Bubendorf, L Nolan, L Glasman, M Leighton, X Miller, G Fehrle, W Raffeld, M Eidelman, O Kallioniemi, OP Srivastava, S Pollard, HB AF Srivastava, M Bubendorf, L Nolan, L Glasman, M Leighton, X Miller, G Fehrle, W Raffeld, M Eidelman, O Kallioniemi, OP Srivastava, S Pollard, HB TI ANX7 as a bio-marker in prostate and breast cancer progression SO DISEASE MARKERS LA English DT Article ID PROTEIN-KINASE-C; SYNEXIN ANNEXIN-VII; SPLICE VARIANTS BRCA1A; WILD-TYPE P53; DICTYOSTELIUM-DISCOIDEUM; SIGNAL-TRANSDUCTION; CHROMAFFIN GRANULES; TISSUE MICROARRAYS; CARCINOMA-CELLS; RB GENE AB The ANX7 gene codes for a Ca2+-activated GTPase, which has been implicated in both exocytotic secretion in cells and control of growth. In this review, we summarize information regarding increased tumor frequency in the Anx7 knockout mice, ANX7 growth suppression of human cancer cell lines, and ANX7 expression in human tumor tissue micro-arrays. The loss of ANX7 is significant in metastatic and hormone refractory prostate cancer compared to benign prostatic hyperplasia. In addition, ANX7 expression has prognostic value for predicting, survival of breast cancer patients. C1 USU, Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. USU, Sch Med, Inst Mol Med, Bethesda, MD 20814 USA. NHGRI, Canc Genet Branch, Mol Genet Sect, NIH, Bethesda, MD 20892 USA. NCRR, Vet Resources Program, NIH, Bethesda, MD 20892 USA. NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Basel, Inst Pathol, CH-4003 Basel, Switzerland. USUHS, Ctr Prostate Dis Res, Bethesda, MD 20814 USA. USUHS, Dept Surg, Bethesda, MD 20814 USA. RP Srivastava, M (reprint author), USU, Sch Med, Dept Anat & Cell Biol, 4301 Jones Bridge Rd, Bethesda, MD 20814 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 NR 46 TC 23 Z9 27 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2001 VL 17 IS 2 BP 115 EP 120 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 491LG UT WOS:000172109400010 PM 11673658 ER PT J AU Verma, M Srivastava, S AF Verma, M Srivastava, S TI Molecular signatures of infectious agents in human cancer SO DISEASE MARKERS LA English DT Editorial Material C1 NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Rockville, MD 20852 USA. RP Verma, M (reprint author), NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Room 3144,Execut Plaza N,6130 Execut Blvd, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2001 VL 17 IS 3 BP 121 EP 122 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 503QC UT WOS:000172808400001 ER PT J AU Mikovits, J Ruscetti, F Zhu, W Bagni, R Dorjsuren, D Shoemaker, R AF Mikovits, J Ruscetti, F Zhu, W Bagni, R Dorjsuren, D Shoemaker, R TI Potential cellular signatures of viral infections in human hematopoietic cells SO DISEASE MARKERS LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; GENE-EXPRESSION; KAPOSIS-SARCOMA; DNA-SEQUENCES; T-CELLS; HTLV-I; LYMPHOMA; LEUKEMIA; VIRUS; HUMAN-HERPESVIRUS-8 AB Expression profiling of cellular genes was performed using a 10,000 cDNA human gene array in order to identify expression changes following chronic infection of human hematopoietic cells with Kapsosi's Sarcoma -associated Virus (KSHV) also known as Human Herpesvirus 8 (HHV8) and Human T cell leukemia virus-1 (HTLV-1). We performed cell-free in vitro infection of primary bone marrow derived CD34+ cells using semi-purified HHV8 and a mature IL-2 dependent T cell line, KIT 225, using highly concentrated viral stocks prepared from an infectious molecular clone of HTLV-1. Thirty days post infection, mRNA was isolated from infected cultures and uninfected controls and submitted for microarray analysis. More than 400 genes were differentially expressed more than two-fold following HHV8 infection of primary bone marrow derived CD34+ cells. Of these 400, interferon regulatory factor 4 (IRF4), cyclin B2, TBP-associated factor, eukaryotic elongation factor and pim 2 were up-regulated more than 3.5 fold. In contrast, less than 100 genes were differentially expressed more than twofold following chronic infection of a mature T cell line with HTLV-1. Of these, only cdc7 was up-regulated more than 3.5 fold. These data may provide insight into cellular si.-natures of infection useful for diagnosis of infection as well as potential targets for therapeutic intervention. C1 Lab Antiviral Drug Mech, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Lab Leukocyte Biol,DBS, Frederick, MD 21702 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD USA. DCTD, Dev Therapeut Program, Screening Technol Branch, Frederick, MD USA. RP Mikovits, J (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Lab Leukocyte Biol,DBS, POB B,Bldg 439, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 27 TC 13 Z9 13 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2001 VL 17 IS 3 BP 173 EP 178 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 503QC UT WOS:000172808400011 PM 11790884 ER PT J AU Verma, M Lambert, PF Srivastava, SK AF Verma, M Lambert, PF Srivastava, SK TI Meeting highlights: National Cancer Institute Workshop on Molecular Signatures of Infectious Agents SO DISEASE MARKERS LA English DT Editorial Material ID HEPATITIS-B VIRUS; HUMAN-PAPILLOMAVIRUS TYPE-31; VIRAL LIFE-CYCLE; TT VIRUS; KAPOSIS-SARCOMA; DNA-SEQUENCES; X PROTEIN; 2-DIMENSIONAL ELECTROPHORESIS; TAX TRANSACTIVATION; UNKNOWN ETIOLOGY C1 NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Rockville, MD 20852 USA. Univ Wisconsin, Sch Med, Mcardle Lab Canc Res, Madison, WI 53706 USA. RP Verma, M (reprint author), NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Execut Plaza N,Room 330E,6130 Execut Blvd, Rockville, MD 20852 USA. NR 83 TC 5 Z9 5 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2001 VL 17 IS 3 BP 191 EP 201 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 503QC UT WOS:000172808400013 PM 11790886 ER PT J AU Srivastava, S Hanash, S AF Srivastava, S Hanash, S TI Global strategies for disease detection and treatment: Proteomics SO DISEASE MARKERS LA English DT Editorial Material C1 NCI, Div Canc Prevent, Canc Biomakers Res Grp, Bethesda, MD 20892 USA. Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. RP Srivastava, S (reprint author), NCI, Div Canc Prevent, Canc Biomakers Res Grp, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2001 VL 17 IS 4 BP 203 EP 204 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 514HZ UT WOS:000173434400001 ER PT J AU Paweletz, CP Trock, B Pennanen, M Tsangaris, T Magnant, C Liotta, LA Petricoin, EF AF Paweletz, CP Trock, B Pennanen, M Tsangaris, T Magnant, C Liotta, LA Petricoin, EF TI Proteomic patterns of nipple aspirate fluids obtained by SELDI-TOF: Potential for new biomarkers to aid in the diagnosis of breast cancer SO DISEASE MARKERS LA English DT Article ID IONIZATION MASS-SPECTROMETRY; RISK; RADIATION; CYTOLOGY; ANTIGEN; HISTORY AB Nipple aspirate fluid (NAF) has been used for many years as a potential non-invasive method to identify markers for breast cancer risk or early detection. Because individual markers have not been optimal, we are exploring the use of surface enhanced laser desorption and ionization time of flight (SELDI-TOF) mass spectrometry to identify patterns of proteins that might define a proteomic signature for breast cancer. SELDI-TOF was used to analyze a study set of NAF samples that included 12 women with breast cancer and 15 healthy controls (the latter included three women with an abnormal mammogram but subsequent normal biopsy). In this preliminary report, we present data showing that SELDI analysis of NAF is rapid, reproducible, and capable of identifying protein signatures that appear to differentiate NAF samples from breast cancer patients and healthy controls, including those with an abnormal mammogram who were later proven to be biopsy normal. C1 US FDA, CBER, Div Therapeut Prot, Tissue Prote, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. Johns Hopkins Univ, Dept Urol, Baltimore, MD 21287 USA. Georgetown Univ, Dept Surg, Washington, DC 20007 USA. Sibley Hosp, Dept Surg, Washington, DC 20010 USA. RP Petricoin, EF (reprint author), US FDA, CBER, Div Therapeut Prot, Tissue Prote, Bethesda, MD 20892 USA. NR 24 TC 206 Z9 237 U1 1 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2001 VL 17 IS 4 BP 301 EP 307 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 514HZ UT WOS:000173434400011 PM 11790897 ER PT J AU Cattaneo, M Sorio, C Malferrari, G Rogozin, IB Bernard, L Scarpa, A Zollo, M Biunno, I AF Cattaneo, M Sorio, C Malferrari, G Rogozin, IB Bernard, L Scarpa, A Zollo, M Biunno, I TI Cloning and functional analysis of SEL1L promoter region, a pancreas-specific gene SO DNA AND CELL BIOLOGY LA English DT Article ID HOMEODOMAIN TRANSCRIPTION FACTOR; CELL FATE; CAENORHABDITIS-ELEGANS; BETA-CELLS; NOTCH; DIFFERENTIATION; DROSOPHILA; LIGANDS; SEL-1; MAPS AB We examined the promoter activity of SEL1L, the human ortholog of the C, elegans gene sel-1, a negative regulator of LIN-12/NOTCH receptor proteins. To understand the relation in SEL1L transcription pattern observed in different epithelial cells, we determined the transcription start site and sequenced the 5' flanking region. Sequence analysis revealed the presence of consensus promoter elements-CC boxes and a CAAT box-but the absence of a TATA motif, Potential binding sites for transcription factors that are involved in tissue-specific gene expression were identified, including: activator protein-2 (AP-2), hepatocyte nuclear factor-3 (HNF3 beta), homeobox Nkx2-5 and GATA-1. Transcription activity of the TATA-less SEL1L promoter was analyzed by transient transfection using luciferase reporter gene constructs. A core basal promoter of 302 bp was sufficient for constitutive promoter activity in all the cell types studied. This genomic fragment contains a CAAT and several GC boxes. The activity of the SEL1L promoter was considerably higher in mouse pancreatic beta cells (beta TC3) than in several human pancreatic neoplastic cell lines; an even greater reduction of its activity was observed in cells of nonpancreatic origin. These results suggest that SEL1L promoter may be a useful tool in gene therapy applications for pancreatic pathologies. C1 CNR, Ist Tecnol Biomed Avanzate, I-20090 Milan, Italy. Univ Verona, Dipartimento Patol, Sez Patol Gen & Anat Patol, I-37100 Verona, Italy. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Telethon Inst Genet & Med, Milan, Italy. RP Biunno, I (reprint author), CNR, Ist Tecnol Biomed Avanzate, Via Filli Cervi 93, I-20090 Milan, Italy. RI Bernard, Loris/K-5953-2014; scarpa, aldo/K-6832-2016; OI scarpa, aldo/0000-0003-1678-739X; Sorio, Claudio/0000-0003-2739-4014 FU Telethon [TGM00Z05, TGM06S01] NR 30 TC 12 Z9 12 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD JAN PY 2001 VL 20 IS 1 BP 1 EP 9 DI 10.1089/10445490150504648 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 399EW UT WOS:000166799500001 PM 11242538 ER PT J AU Kitanaka, J Wang, XB Kitanaka, N Hembree, CM Uhl, GR AF Kitanaka, J Wang, XB Kitanaka, N Hembree, CM Uhl, GR TI Genomic organization of the murine G protein beta subunit genes and related processed pseudogenes SO DNA SEQUENCE LA English DT Article DE GTP-binding protein beta subunit; mouse gene; pseudogene; genomic structure ID ALPHA-SUBUNIT; CDNA AB The functional significance of heterotrimeric guanine nucleotide binding protein (G protein) for the many physiological processes including the molecular mechanisms of drug addiction have been described. In investigating the changes of mRNA expression after acute psychostimulant administration, we previously identified a cDNA encoding a G protein beta1 subunit (Gbeta1) that was increased up to four-fold in certain brain regions after administration of psychostimulants. The mouse Gbeta1 gene (the mouse genetic symbol, GNB1) was mapped to chromosome 4, but little was known of its genetic features. To characterize the GNB1 gene further, we have cloned and analyzed the genomic structures of the mouse GNB1 gene and its homologous sequences. The GNB1 gene spans at least 50 kb, and consists of 12 exons and 11 introns. The exon/intron boundaries were determined and found to follow the GT/AG rule. Exons 3-11 encode the Gbeta1 protein, and the exon 2 is an alternative, resulting in putative two splicing variants. Although intron 11 is additional for GNB1 compared with GNB2 and GNB3, the intron positions within the protein coding region of GNB1, GNB2 and GNB3 are identical, suggesting that GNB1 should have diverged from the ancestral gene family earlier than the genes for GNB2 and GNB3. We also found the 5'-truncated. processed pseudogenes with 71-89% similarities to GNB1 mRNA sequence, suggesting that the truncated cDNA copies, which have been reverse-transcribed from a processed mRNA for GNB1, might have been integrated into several new locations in the mouse genome. C1 Natl Inst Drug Abuse, Mol Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Kitanaka, J (reprint author), Hyogo Med Univ, Dept Pharmacol, 1-1 Mukogawa Cho, Nishinomiya, Hyogo 6638501, Japan. NR 17 TC 5 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK,, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-5179 J9 DNA SEQUENCE JI DNA Seq. PY 2001 VL 12 IS 5-6 BP 345 EP 354 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 520AU UT WOS:000173758400006 PM 11913780 ER PT S AU Kim, J Le, DX Thoma, GR AF Kim, J Le, DX Thoma, GR BE Kantor, PB Lopresti, DP Zhou, J TI Automated labeling in document images SO DOCUMENT RECOGNITION AND RETRIEVAL VIII SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 8th Annual Document Recognition and Retrieval Conference CY JAN 24-25, 2001 CL SAN JOSE, CA SP Soc Imaging Sci & Technol, SPIE DE OCR; automated data entry; automated zoning; automated labeling; rule-based algorithm; MARS; NLM AB The National Library of Medicine (NLM) is developing an automated system to produce bibliographic records for its MEDLINE (R) database. This system, named Medical Article Record System (MARS), employs document image analysis and understanding techniques and optical character recognition (OCR). This paper describes a key module in MARS called the Automated Labeling (AL) module, which labels all zones of interest (title, author, affiliation, and abstract) automatically. The AL algorithm is based on 120 rules that are derived from an analysis of journal page layouts and features extracted from OCR output. Experiments carried out on more than 11,000 articles in over 1,000 biomedical journals show the accuracy of this rule-based algorithm to exceed 96%. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Kim, J (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 12 TC 13 Z9 13 U1 1 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3985-1 J9 P SOC PHOTO-OPT INS PY 2001 VL 4307 BP 111 EP 122 PG 12 WC Computer Science, Information Systems; Computer Science, Software Engineering SC Computer Science GA BR90Y UT WOS:000168019700011 ER PT S AU Ford, G Hauser, S Le, DX Thoma, GR AF Ford, G Hauser, S Le, DX Thoma, GR BE Kantor, PB Lopresti, DP Zhou, J TI Pattern matching techniques for correcting low confidence OCR words in a known context SO DOCUMENT RECOGNITION AND RETRIEVAL VIII SE Proceedings of SPIE LA English DT Proceedings Paper CT 8th Annual Document Recognition and Retrieval Conference CY JAN 24-25, 2001 CL SAN JOSE, CA SP Soc Imaging Sci & Technol, SPIE DE automated data extraction; scanning; OCR; NLM; MARS; pattern matching AB A commercial OCR system is a key component of a system developed at the National Library of Medicine for the automated extraction of bibliographic fields from biomedical journals. This 5-engine OCR system, while exhibiting high performance overall, does not reliably convert very small characters, especially those that are in italics. As a result, the "affiliations" field that typically contains such characters in most journals, is not captured accurately, and requires a disproportionately high manual input. To correct this problem, dictionaries have been created from words occurring in this field (e.g., university, department, street addresses, names of cities, etc.) from 230,000 articles already processed. The OCR output corresponding to the affiliation field is then matched against these dictionary entries by approximate string-matching techniques, and the ranked matches are presented to operators for verification. This paper outlines the techniques employed and the results of a comparative evaluation. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Natl Lib Med, Bethesda, MD 20894 USA. EM hauser@nlm.nih.gov NR 7 TC 5 Z9 5 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3985-1 J9 PROC SPIE PY 2001 VL 4307 BP 241 EP 249 PG 9 WC Computer Science, Information Systems; Computer Science, Software Engineering SC Computer Science GA BR90Y UT WOS:000168019700025 ER PT J AU Karrow, NA McCay, JA Brown, RD Musgrove, DL Germolec, DR White, KL AF Karrow, NA McCay, JA Brown, RD Musgrove, DL Germolec, DR White, KL TI Evaluation of the immunomodulatory effects of the macrolide antibiotic, clarithromycin, in female B6C3F1 mice: A 28-day oral gavage study SO DRUG AND CHEMICAL TOXICOLOGY LA English DT Article ID ERYTHROMYCIN; AZITHROMYCIN; INHIBITION AB The macrolide antibiotic, clarithromycin, is used extensively to treat bacterial infections associated with pneumonia, duodenal ulcers, and the advanced stages of human immunodeficiency viral (HIV) infection. In addition to its antimicrobial properties, several studies have indicated that clarithromycin also has anti-inflammatory and immunomodulatory properties. In this study, clarithromycin's immunomodulatory properties were evaluated using female B6C3F1 mice and a panel of immune assays that were designed to evaluate potential changes in innate, and acquired cellular and humoral immune responses. Female B6C3F1 mice were treated daily by gavage with clarithromycin (0, 125. 250, and 500 mg/kg) for 28 days then evaluated for immunomodulation. Minimal immunological changes were observed after 28 days of treatment. A slight increase in the number of spleen antibody-forming cells was observed at the 250 mg/kg treatment level, but not at other doses. Serum IgM levels were unaffected by the clarithromycin treatment. A significant increase in the number of splenic macrophages was also observed in mice treated with 125 mg/kg of clarithromycin, but this increase was not observed at the other treatment levels. Innate and cell-mediated immunity, as measured by natural killer cell activity, and mixed leukocyte and cytotoxic T cell response, respectively, were unchanged following treatment with clarithromycin. These results suggest that the immune system is not a target for clarithromycin at doses of 500 mg/kg or below. C1 Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. NIEHS, Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP White, KL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Med Coll Virginia Campus, Richmond, VA 23298 USA. FU NIEHS NIH HHS [ES55387] NR 23 TC 3 Z9 3 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0148-0545 J9 DRUG CHEM TOXICOL JI Drug Chem. Toxicol. PY 2001 VL 24 IS 1 BP 19 EP 37 DI 10.1081/DCT-100103083 PG 19 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy; Toxicology SC Chemistry; Pharmacology & Pharmacy; Toxicology GA 455UN UT WOS:000170046300002 PM 11307632 ER PT J AU Guo, TL McCay, JA Karrow, NA Brown, RD Musgrove, DL Luebke, RW Germolec, DR White, KL AF Guo, TL McCay, JA Karrow, NA Brown, RD Musgrove, DL Luebke, RW Germolec, DR White, KL TI Immunotoxicity of sodium bromate in female B6C3F1 mice: A 28-day drinking water study SO DRUG AND CHEMICAL TOXICOLOGY LA English DT Article DE sodium bromate; reticulocytes; immunotoxicity; macrophage activity; disinfection by-product ID POTASSIUM BROMATE; RATS; CYCLOPHOSPHAMIDE; CARCINOGENICITY AB Bromate is one of the water disinfection by-products (DBPs) produced during the process of ozonation. The purpose of this study was to evaluate the immunotoxic potential of sodium bromate (SB) in female B6C3F1 mice. SE was administered in the drinking water for 28 days at doses of 80-800 mg/l. There was no difference in drinking water consumption between the animals exposed to SE and the tap water controls. Exposure to SE did not produce any signs of overt toxicity. Furthermore, no significant differences were observed in body weight, body weight gain, or the weights of thymus, liver, kidneys or lungs. No gross pathological lesions were observed in SE-treated animals. However, animals exposed to SE had a significant increase in absolute (28%) and relative (26%) spleen weights. The erythrocyte count, hemoglobin, hematocrit, mean corpuscular volume (MCV), platelet count, total leukocyte count, and counts of differential leukocytes were unaffected by SE. A dose-related increase in reticulocytes was observed following exposure to SE with the greatest increase (78%) observed at the highest dose level. Overall, there were no changes in the absolute number of total T cells, CD4(+)CD8(-) T cells, CD4(-)CD8(+) T cells, natural killer (NK) cells and macrophages. Exposure to SE did not affect the percentage of B cells, although a slight increase in absolute number of B cells at the dose of 600 mg/l was observed. There was no alteration in IgM antibody-forming cell (AFC) response. mixed leukocyte reaction (MLR) and NK cell activity after exposure to SE. When the activity of peritoneal macrophages, unstimulated or stimulated with IFN-gamma and LPS, was evaluated using the cytotoxic/cytostatic assay of B16F10 tumor cells, the suppressive effect of macrophages on the proliferation of B16F10 tumor cells was decreased after exposure to SE. In conclusion, SE, when administered in the drinking water at doses from 80 mg/l to 800mg/l, produced minimal toxicological and immunotoxic effects in female B6C3F1 mice. C1 Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. US EPA, Res Triangle Pk, NC 27711 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP White, KL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, POB 980613, Richmond, VA 23298 USA. NR 17 TC 5 Z9 6 U1 0 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0148-0545 J9 DRUG CHEM TOXICOL JI Drug Chem. Toxicol. PY 2001 VL 24 IS 2 BP 129 EP 149 DI 10.1081/DCT-100102606 PG 21 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy; Toxicology SC Chemistry; Pharmacology & Pharmacy; Toxicology GA 455UP UT WOS:000170046400005 PM 11360431 ER PT J AU Karrow, NA Guo, TL McCay, JA Johnson, GW Brown, RD Musgrove, DL Germolec, DR Luebke, RW White, KL AF Karrow, NA Guo, TL McCay, JA Johnson, GW Brown, RD Musgrove, DL Germolec, DR Luebke, RW White, KL TI Evaluation of the immunomodulatory effects of the disinfection by-product, sodium chlorite, in female B6C3F1 mice: A drinking water study SO DRUG AND CHEMICAL TOXICOLOGY LA English DT Article DE sodium chlorite; drinking water; immunomodulation; B6C3F1 mice ID INVITRO; RATS AB Sodium chlorite is an inorganic by-product of chlorine dioxide formed during the chlorination of drinking water. Relatively little is known about the adverse health effects of exposure to sodium chlorite in drinking water. In this study, we evaluated sodium chlorite's immunomodulatory properties using female B6C3F1 mice and a panel of immune assays that were designed to evaluate potential changes in innate and acquired cellular and humoral immune responses. Female B6C3F1 mice were exposed to sodium chlorite in their drinking water (0, 0.1, 1, 5, 15, and 30 mg/L) for 28 days, and then evaluated for immunomodulation. Overall, minimal toxicological and immunological changes were observed after exposure to sodium chlorite. Increases in the percentages of blood reticulocytes, and the relative spleen weights were both observed at different sodium chlorite treatment levels: however, these increases were not dose-dependent. An increasing trend in the number of spleen antibody-forming cells was observed over the range of sodium chlorite concentrations. This increase was not, however, significant at any individual treatment level, and was not reflected by changes in serum IgM levels. A significant increase (26%) in the total number of splenic CD8(+) cells was observed in mice treated with 30 mg/L of sodium chlorite, but not at the other concentrations. Splenic mixed leukocyte response and peritoneal macrophage activity were unaffected by sodium chlorite. Lastly, exposure to sodium chlorite did not affect natural killer cell activity, although a decrease in augmented natural killer cell activity (42%) was observed at the lowest sodium chlorite treatment level. These results suggest that sodium chlorite, within the range 0.1-30mg/L, produces minimal immunotoxicity in mice. C1 Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. NIEHS, Toxicol Lab, Res Triangle Pk, NC 27709 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Expt Toxicol Div, Immunotoxicol Branch, Res Triangle Pk, NC 27711 USA. RP White, KL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Med Coll Virginia Campus, Richmond, VA 23298 USA. FU NIEHS NIH HHS [ES55094] NR 20 TC 1 Z9 1 U1 0 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0148-0545 J9 DRUG CHEM TOXICOL JI Drug Chem. Toxicol. PY 2001 VL 24 IS 3 BP 239 EP 258 DI 10.1081/DCT-100103722 PG 20 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy; Toxicology SC Chemistry; Pharmacology & Pharmacy; Toxicology GA 455UQ UT WOS:000170046500003 PM 11452397 ER PT J AU Bolego, C Centemeri, C Abbracchio, MP Ceruti, S Cattabeni, F Jacobson, KA Puglisi, L Rovati, GE Burnstock, G Nicosia, S AF Bolego, C Centemeri, C Abbracchio, MP Ceruti, S Cattabeni, F Jacobson, KA Puglisi, L Rovati, GE Burnstock, G Nicosia, S TI Two distinct P2Y receptors are involved in purine- and pyrimidine-evoked Ca2+ elevation in mammalian brain astrocytic cultures SO DRUG DEVELOPMENT RESEARCH LA English DT Article; Proceedings Paper CT PURINES 2000 Meeting CY JUL 09-13, 2000 CL MADRID, SPAIN SP PURINES DE rat; UTP; UDP; MRS2179; Ca2+ signalling ID FIBROBLAST GROWTH-FACTOR; PHOSPHOLIPASE-C; NUCLEOTIDE RECEPTOR; SIGNAL-TRANSDUCTION; CALCIUM CHANNELS; RAT STRIATUM; ATP; PATHWAYS; CLONING; CELLS AB ATP and 2-methyl-thio-ATP (2-Me-SATP) increase cytosolic calcium concentrations ([Ca2+](i)) in rat striatal astrocytes (Centemeri et al. (1997) Br J Pharmacol 121:1700-1706). The aim of the present study was to: (1) characterize pyrimidine-induced [Ca2+](i) increases in the same experimental system, and (2) try to identify the multiple P2Y receptor subtypes mediating Ca2+ mobilization. UDP and UTP triggered a concentration-dependent [Ca2+](i) elevation (EC(50)s = 0.58 muM +/- 0.4 and 31 muM +/- 6, respectively). Pyrimidine-evoked [Ca2+](i) elevation was solely due to mobilization from intracellular stores, because: (1) removing calcium from extracellular medium or (2) blocking its influx with Ni2+ did not modify UTP responses; (3) the store-depleting agent thapsigargin completely abolished UTP-evoked [Ca2+](i) increments. Guanosine-5'-O-(2-thiodiphosphate) partially inhibited the UTP response, whereas pertussis toxin (PTx) had no effect. The phospholipase C inhibitor U-73122 significantly reduced the UTP-evoked [Ca2+](i) rise. Computer-assisted analysis indicated that the UTP and UDP responses are mediated by a single receptor, while ATP and 2-Me-SATP interact with two distinct receptors. The selective P2Y(1) receptor antagonist MRS2179 abolished the ATP higher potency component. Sequential challenges with the same nucleotides resulted in almost complete homologous desensitization. Pre-exposure to UTP lowered the subsequent responses to either ATP or 2-Me-SATP. Maximally active concentrations of UTP and ATP were not additive. In conclusion, [Ca2+](i) elevation in astrocytes by purines and pyrimidines is mediated by two distinct P2Y receptors, likely the P2Y(1) and P2Y(6), subtypes. Drug Dev. Res. 52:122-132, 2001. (C) 2001 Wiley-Liss, Inc. C1 Univ Milan, Dept Pharmacol Sci, I-20133 Milan, Italy. NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, Bethesda, MD USA. Royal Free Hosp, Sch Med, Autonom Neurosci Inst, London, England. RP Abbracchio, MP (reprint author), Univ Milan, Dept Pharmacol Sci, Via Balzaretti 9, I-20133 Milan, Italy. RI Ceruti, Stefania/A-6376-2008; Jacobson, Kenneth/A-1530-2009; Abbracchio, Maria Pia/B-9342-2014; Pinna, Annalisa/J-4212-2012; OI Ceruti, Stefania/0000-0003-1663-4211; Jacobson, Kenneth/0000-0001-8104-1493; Abbracchio, Maria Pia/0000-0002-7833-3388; Pinna, Annalisa/0000-0002-4911-1735; morelli, micaela/0000-0003-0394-5782 NR 49 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 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD JAN-FEB PY 2001 VL 52 IS 1-2 BP 122 EP 132 DI 10.1002/ddr.1106 PG 11 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 429TE UT WOS:000168532400015 ER PT J AU Jacobson, KA AF Jacobson, KA TI Probing adenosine and P2 receptors: Design of novel purines and nonpurines as selective ligands SO DRUG DEVELOPMENT RESEARCH LA English DT Article; Proceedings Paper CT PURINES 2000 Meeting CY JUL 09-13, 2000 CL MADRID, SPAIN SP PURINES DE G-protein-coupled receptors; nucleoides; nucleotides; structure activity relationships; template; purines; adenosine receptors ID P2Y(1) RECEPTOR; A(3) RECEPTORS; HUMAN A(2B); NUCLEOTIDE DERIVATIVES; CARBOXYLIC CONGENER; BIOLOGICAL-ACTIVITY; ANTAGONISTS; AGONISTS; ANALOGS; POTENT AB Recent approaches to the design of selective agonists and antagonists at adenosine (AR) and P2 receptors include both modifying known receptor ligands and searching for structurally diverse antagonists. The ribose-like moiety of nucleoside/nucleotide derivatives was rigidified with a methanocarba (mc) modification, to constrain the ring in a conformation that was favored in binding to ARs or P2Y receptors. (N)-mc analogs of various N-6-substituted adenosine derivatives, including cyclopentyl and 3-iodobenzyl, in which the parent compounds are potent agonists at either A(1) or A(3)ARs, respectively, retained high receptor affinity and selectivity. For nucleotides acting as P2Y(1) receptor antagonists, the (N)-mc analog MRS 2279 ((1R,2S,4S,5S)-1-[(phosphato)methyl]-4-(2-chloro-6-methylaminopurin-9-yl) bicyclo[3.1.0]-hexane-2-phosphate) proved to be a selective antagonist, with an IC50 of 52 nM. Other ribose substitutions possible in P2Y1 receptor antagonists were 4- and 6-membered rings and acyclic derivatives. High affinity for the A(2B)AR was achieved through the formation of anilides and benzylamides of XCC (8-[4-[[[carboxy]methyl]oxy]phenyl]1,3-dipropylxanthine). A p-cyanoaniline derivative (MRS 1754, K-i value 1.97 nM) was 205-, 255-, and 289-fold selective for the human A(2B)ARS vs. human A(1)/A(2A)/A(3) ARs, respectively. A template approach based on the pyridine family, i.e., 1,4-dihydropyridine nucleus and the corresponding 3,5-diacylpyridines, was used for the design of novel adenosine antagonists. The pyridine derivative MRS 1523 (5-propyl-2-ethyl-4-propyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate) was shown to be a selective antagonist at the rat A(3)AR as well as the human A(3)AR. Chemical libraries were screened computationally and using binding assays to identify novel AR antagonists. Molecular modeling of ARs and P2Y receptors provided hypotheses for ligand docking. Drug Dev. Res. 52:178-186, 2001. Published 2001 Wiley-Liss, Inc. C1 NIDDK, Mol Recognit Sect, LBC, NIH, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, 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 41 TC 7 Z9 7 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 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD JAN-FEB PY 2001 VL 52 IS 1-2 BP 178 EP 186 DI 10.1002/ddr.1113 PG 9 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 429TE UT WOS:000168532400022 ER PT J AU Liang, BT Stewart, D Jacobson, KA AF Liang, BT Stewart, D Jacobson, KA TI Adenosine A(1) and A(3) receptors: Distinct cardioprotection SO DRUG DEVELOPMENT RESEARCH LA English DT Article; Proceedings Paper CT PURINES 2000 Meeting CY JUL 09-13, 2000 CL MADRID, SPAIN SP PURINES DE cardioprotection; cardiac myocytes; A(3) receptor; phospholipase D ID PROTEIN-KINASE-C; K-ATP CHANNELS; ISCHEMIC MYOCARDIAL INJURY; ISOLATED RAT-HEART; CONSCIOUS RABBITS; GUINEA-PIG; PHARMACOLOGICAL CHARACTERIZATION; INTRACORONARY ADENOSINE; NONXANTHINE ANTAGONIST; SELECTIVE ANTAGONISTS AB Adenosine is released in large amounts during myocardial ischemia and exerts patent cardioprotective effects in the heart. Although these observations on adenosine have been known for a long time, how adenosine acts to achieve its antiischemic effect remains incompletely understood. Recent advances in the chemistry and pharmacology of adenosine receptor ligands have provided important and novel information on the function of adenosine receptor subtypes in the cardiovascular system. The development of model systems for the cardiac actions of adenosine has yielded important insights into its mechanism of action and have begun to elucidate the sequence of signaling events from receptor activation to the actual exertion of its cardioprotective effect. The goal of the current article is to review recent advances on the cellular and molecular mechanisms that mediate the cardiac actions of adenosine and to show the cardioprotective effect of novel adenosine ligands. Drug Dev Res. 52:366-378, 2001. (C) 2001 Wiley-Liss, Inc. C1 Univ Penn, Med Ctr, Dept Med, Div Cardiovasc, Philadelphia, PA 19104 USA. NIH, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Liang, BT (reprint author), Univ Penn, Med Ctr, Dept Med, Div Cardiovasc, 956 BRBII-III,421 Curie Blvd, Philadelphia, PA 19104 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 125 TC 9 Z9 9 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD JAN-FEB PY 2001 VL 52 IS 1-2 BP 366 EP 378 DI 10.1002/ddr.1136 PG 13 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 429TE UT WOS:000168532400045 ER PT B AU Cragg, GM Newman, DJ AF Cragg, GM Newman, DJ BE Lin, Y TI Natural products drug discovery and development at the United States National Cancer Institute SO DRUG DISCOVERY AND TRADITIONAL CHINESE MEDICINE: SCIENCE, REGULATION, AND GLOBALIZATION LA English DT Proceedings Paper CT 1st International Conference on Traditional Chinese Medicine CY AUG 30-SEP 02, 2000 CL UNIV MARYLAND, COLLEGE PK, MD SP NIH, Natl Ctr Complementary & Alternat Med, Minist Sci & Technol, Beijing, Pharmaceut Ind Technol & Dev Ctr, Taipei, Pfizer Inc, Taiwan Sugar Corp,, UBI Asia, Taipei, Tauwab Sugar Corp, King Car Food Ind Co Ltd, Chainex Metal Factory Co Ltd, Sinphar Pharmaceut, Chinese Univ Hong Kong, Inst Chinese Med, Hong Kong Econ & Trade Off, Academia Sinica, Inst BioAgr Sci, Peking Univ HO UNIV MARYLAND ID ANTICANCER; AGENTS; TAXOL AB Between 1960 and 1982, the National Cancer Institute (NCI) screened over 180,000 microbial-derived, some 16,000 marine organism-derived, and over 114,000 plant-derived extracts. A number of clinically effective chemotherapeutic agents were developed, mainly through collaborative efforts with the public and private sectors. These agents include paclitaxel, camptothecin derivatives, various anthracyclines, bleomycin, actinomycin and mitomycin. Since 1986, collections of plants and marine invertebrates have been performed in over 25 tropical and subtropical countries worldwide through contracts with botanical and marine biological organizations, working in close collaboration with source country organizations and subject to agreements with the source country authorities. Over 120,000 extracts are stored at low temperatures in the NCI Natural Products Repository and are made available to the scientific community for testing in screens related to all human diseases, subject to the signing of Material Transfer Agreements, which protects the rights of all parties, particularly those of the source countries. In addition, Memoranda of Understanding (MOU) have been signed with qualified organizations in over ten source countries for direct collaboration in the drug discovery and development process. A major goal of these collaborations is to promote drug discovery in the source country, with NCI collaborating in the preclinical and clinical development stages. C1 NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Nat Prod Branch, Frederick, MD 21702 USA. RP Cragg, GM (reprint author), NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Nat Prod Branch, Suite 206,POB B, Frederick, MD 21702 USA. NR 26 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC PUBLISHERS PI NORWELL PA 101 PHILIP DRIVE, ASSINIPPI PARK, NORWELL, MA 02061 USA BN 0-7923-7411-8 PY 2001 BP 19 EP 32 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BS88L UT WOS:000171315700003 ER PT B AU Yang, SS Cragg, GM Newman, DJ AF Yang, SS Cragg, GM Newman, DJ BE Lin, Y TI The camptothecin experience: From Chinese medicinal plants to potent anti-cancer drugs SO DRUG DISCOVERY AND TRADITIONAL CHINESE MEDICINE: SCIENCE, REGULATION, AND GLOBALIZATION LA English DT Proceedings Paper CT 1st International Conference on Traditional Chinese Medicine CY AUG 30-SEP 02, 2000 CL UNIV MARYLAND, COLLEGE PK, MD SP NIH, Natl Ctr Complementary & Alternat Med, Minist Sci & Technol, Beijing, Pharmaceut Ind Technol & Dev Ctr, Taipei, Pfizer Inc, Taiwan Sugar Corp,, UBI Asia, Taipei, Tauwab Sugar Corp, King Car Food Ind Co Ltd, Chainex Metal Factory Co Ltd, Sinphar Pharmaceut, Chinese Univ Hong Kong, Inst Chinese Med, Hong Kong Econ & Trade Off, Academia Sinica, Inst BioAgr Sci, Peking Univ HO UNIV MARYLAND ID DNA TOPOISOMERASE-I; CLEAVAGE; CYTOTOXICITY; NSC-100880; BREAKS AB Camptothecin is a potent natural product based anticancer agent isolated from an organic extract of the bark of a Chinese tree, Camptotheca acuminata, Decaisne (Nyssaceae). The chemical identification of camptothecin was first reported in 1966 by Wall et al. (1) as a plant alkaloid which showed strong potency against a number of cancer cells derived from leukemia, small cell lung cancer, and colon and rectal cancer. This communication describes the drug discovery and development process of camptothecin from Camptotheca acuminata at the NCI in collaboration with Monroe E. Wall's group of the Research Triangle Institute and other laboratories facilitated by NCI support. This led to the eventual development of several potent camptothecin analogs, 9-amino camptothecin, topotecan, irinotecan, and rubitecan, which have been approved for cancer therapy against diverse cancer types including different leukemias and lymphoma, small cell lung carcinoma, colon and rectal cancer, cancer of the central nervous system, renal cell carcinoma, ovarian and breast cancer in humans. Topotecan and irinotecan are also currently used in a wide spectrum of clinical trials in patients with metastatic cancers. The resolution of camptothecin action mechanism targeting topoisomerase I provided vital information in cancer drug action, and stimulated novel and rational cancer drug design and development. C1 NCI, Nat Prod Branch, NIH, Bethesda, MD 20817 USA. RP Yang, SS (reprint author), NCI, Nat Prod Branch, NIH, Bethesda, MD 20817 USA. NR 25 TC 0 Z9 0 U1 0 U2 1 PU KLUWER ACADEMIC PUBLISHERS PI NORWELL PA 101 PHILIP DRIVE, ASSINIPPI PARK, NORWELL, MA 02061 USA BN 0-7923-7411-8 PY 2001 BP 61 EP 74 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BS88L UT WOS:000171315700007 ER PT J AU Capri, S Ceci, A Terranova, L Merlo, F Mantovani, L AF Capri, S Ceci, A Terranova, L Merlo, F Mantovani, L CA Italian Grp Pharmacoecon Studies TI Guidelines for economic evaluations in Italy: Recommendations from the Italian Group of Pharmacoeconomic Studies SO DRUG INFORMATION JOURNAL LA English DT Article DE pharmacoeconomics; Italy; Italian Group for Pharmacoeconomic Studies ID COST-EFFECTIVENESS ANALYSIS; CONFIDENCE-INTERVALS; HEALTH-CARE; RATIOS; LIFE; SUBMISSIONS; SEARCH; BMJ AB Since 1997, in order for a new drug to obtain its price and reimbursement in Italy, the negotiation between authorities and the pharmaceutical industry must include an economic evaluation. The economic evaluation study leads to price and reimbursement negotiations together with such other requirements as the price of the new drug in other countries, the impact on the domestic market in terms of public pharmaceutical expenditure, and the effects on the national economy (employment and investments). In response to the need to set methodological standards for the economic evaluation of drugs a group of about 40 experts (the Italian Group for Pharmacoeconomic Studies) made up of representatives of the regulator, authorities and ministries, academia, and the industry prepared recommendations concerning the methodology and the presentation of pharmacoeconomic studies. The principles were intensively reviewed and discussed during a number of workshops and meetings throughout one year and then finally and officially presented to the regulatory authorities. The elements which must be contained in each study submitted to the authorities are briefly described in this paper considering the main theoretical and regulatory contributions found in the literature. In particular the economic analyses suggested are cost-effectiveness and cost-utility, and they must be applied from the points of view of both society and the Italian National Health Service. Even though pragmatic economic-clinical trials are preferred, given the difficulties in releasing these kinds of studies for drugs which have just been authorized the use of models is suggested where satisfying a series of requirements (the reproducibility of the results by the regulatory commission, detailed description of the methodology and the intermediate results, etc.). Preference is given to microcosting, that is, cost measurement performed at the health care provider level (eg, hospitals), from which representative data at the national level cart be obtained. In terms of the presentation of an economic evaluation, a synthesis of the study must be prepared on the basis of a detailed list of issues in order to facilitate evaluation of the study by the regulatory authorities. The approach followed by the Italian Group for Pharmacoeconomic Studies is based on the belief that only the recommendations prepared with the active contributions of all subjects interested in the economic evaluation of drugs are likely to be efficiently applied and disseminated. C1 Univ Pavia, Postgrad Sch Regulatory Disciplines, I-27100 Pavia, Italy. BETA Biomed Technol Assessement, Genoa, Italy. Italian Assoc Pharmaceut Ind, Rome, Italy. Natl Canc Inst, IST, Genoa, Italy. Univ Milan, Ctr Pharmacoecon, Milan, Italy. RP Capri, S (reprint author), Univ Pavia, Postgrad Sch Regulatory Disciplines, Piazza Botta 11, I-27100 Pavia, Italy. OI Bruzzi, Paolo/0000-0002-7874-2077; Mantovani, Lorenzo Giovanni/0000-0003-3866-8199 NR 44 TC 43 Z9 44 U1 4 U2 7 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD JAN-MAR PY 2001 VL 35 IS 1 BP 189 EP 201 PG 13 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 406NW UT WOS:000167222900022 ER PT J AU Duffel, MW Marshall, AD McPhie, P Sharma, V Jakoby, WB AF Duffel, MW Marshall, AD McPhie, P Sharma, V Jakoby, WB TI Enzymatic aspects of the phenol (aryl) sulfotransferases SO DRUG METABOLISM REVIEWS LA English DT Review ID TYROSINE-ESTER SULFOTRANSFERASE; STEREOSELECTIVE SULFATE CONJUGATION; LIVER ESTROGEN SULFOTRANSFERASE; HUMAN DOPAMINE SULFOTRANSFERASE; SUBSTRATE-SPECIFICITY; MOLECULAR-CLONING; CRYSTAL-STRUCTURE; BACTERIAL EXPRESSION; RAT-LIVER; FORM PHENOLSULFOTRANSFERASE AB The sulfotransferases that are active in the metabolism of xenobiotics represent a large family of enzymes that catalyze the transfer of the sulfuryl group from 3'-phosphoadenosine 5'-phosphosulfate to phenols, to primary and secondary alcohols, to several additional oxygen-containing functional groups, and to amines. Restriction of this review to the catalytic processes of phenol or aryl sulfotransferases does not really narrow the field, because these enzymes have overlapping specificity, not only for specific compounds, but also for multiple functional groups. The presentation aims to provide an overview of the wealth of phenol sulfotransferases that are available for study but concentrates on the enzymology of rat and human enzymes, particularly on the predominant phenol sulfotransferase from rat liver. The kinetics and catalytic mechanism of the rat enzyme is extensively reviewed and is compared with observations from other sulfotransferases. C1 NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. Univ Iowa, Coll Pharm, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. NIDDKD, Lab Genet & Biochem, NIH, Bethesda, MD 20892 USA. RP Jakoby, WB (reprint author), NIDDKD, Lab Cell Biochem & Biol, NIH, Bldg 8,Room 311, Bethesda, MD 20892 USA. RI Duffel, Michael/E-6066-2015 OI Duffel, Michael/0000-0002-6079-7459 FU NCI NIH HHS [CA38683, R01 CA038683] NR 95 TC 46 Z9 49 U1 1 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2001 VL 33 IS 3-4 BP 369 EP 395 DI 10.1081/DMR-120001394 PG 27 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 505GQ UT WOS:000172905400006 PM 11768773 ER PT J AU Marchand, C Neamati, N Pommier, Y AF Marchand, C Neamati, N Pommier, Y TI In vitro human immunodeficiency virus type 1 integrase assays SO DRUG-NUCLEIC ACID INTERACTIONS SE METHODS IN ENZYMOLOGY LA English DT Review ID HIV-1 INTEGRASE; COMPLEXES C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Marchand, C (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RI Marchand, Christophe/D-8559-2016 NR 9 TC 49 Z9 50 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2001 VL 340 BP 624 EP 633 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BS72V UT WOS:000170995300032 PM 11494874 ER PT J AU Lee, LM Henderson, DK AF Lee, LM Henderson, DK TI Tolerability of postexposure antiretroviral prophylaxis for occupational exposures to HIV SO DRUG SAFETY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEALTH-CARE WORKERS; ZIDOVUDINE PROPHYLAXIS; INFECTION; PREVENTION; TRANSMISSION; CHEMOPROPHYLAXIS; SEROCONVERSION; EXPERIENCE; INITIATION AB A substantial body of evidence provides support (but not definitive proof of efficacy) for the use of antiretroviral agents as postexposure prophylaxis for occupational exposures to HIV in the healthcare workplace. Despite the lack of definitive evidence of the efficacy of these agents in this setting, over the past decade this intervention has become the standard of care for healthcare workers who sustain occupational exposures to HIV. Administration of these agents-even for a relatively short 28-day postexposure course-is often fraught with difficulty. All of the agents currently used for postexposure prophylaxis regimens have substantial adverse effects, and significant adverse effects occur in more than two-thirds of individuals electing prophylaxis. This manuscript reiterates current US Federal Government guidelines for the administration of postexposure prophylaxis, specifically noting that zidovudine plus lamivudine (with or without a protease inhibitor) remains the recommended regimen. The paper summarises the significant toxicities associated with nucleoside reverse transcriptase inhibitors (primarily nausea, vomiting, diarrhoea and bone marrow suppression), non-nucleoside reverse transcriptase inhibitors (rash, fever, gastrointestinal symptoms and hepatitis, including hepatic decompensation necessitating liver transplantation) and protease inhibitors (nausea, vomiting, diarrhoea, abdominal pain, hyperglycaemia, hyperlipidaemia, headache and anorexia). As a class, the antiretroviral agents have an extraordinary number of drug interactions. The non-nucleoside reverse transcriptase inhibitors and the protease inhibitors are metabolised through the cytochrome P450 pathway, and the effects of concomitant administration of protease inhibitors with other agents in the same class are discussed, as well as the effects of concomitant administration of protease inhibitors with non-nucleoside agents. The potential for numerous and medically risky drug interactions emphasises the importance of planning antiretroviral prophylaxis in consultation with practitioners or clinical pharmacists who are skilled in the use of these agents and knowledgeable about the potential for significant drug interactions that could either reduce the benefit of prophylaxis or increase the potential for toxicity. Another common problem encountered by individuals managing postexposure prophylaxis programmes relates to the administration of chemoprophylaxis to a pregnant healthcare worker who has sustained an occupational exposure to HIV. We address what is known about the potential for toxicity and emphasise the recently published warning concerning the deaths of pregnant women and their offspring from lactic acidosis while receiving regimens containing stavudine and didanosine. C1 NIH, Warren G Magnuson Clin Ctr, Off Deputy Director Clin Care, Bethesda, MD 20892 USA. RP Henderson, DK (reprint author), NIH, Warren G Magnuson Clin Ctr, Off Deputy Director Clin Care, Bldg 10,Room 2C146,10 Ctr Dr,MSC-1504, Bethesda, MD 20892 USA. NR 58 TC 23 Z9 25 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2001 VL 24 IS 8 BP 587 EP 597 DI 10.2165/00002018-200124080-00003 PG 11 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 457AW UT WOS:000170115800003 PM 11480491 ER PT J AU Neumeister, A Fleischhacker, WW AF Neumeister, A Fleischhacker, WW TI Once-weekly fluoxetine - A viewpoint SO DRUGS LA English DT Editorial Material ID MAJOR DEPRESSIVE DISORDER; CONTINUATION TREATMENT; PRIMARY-CARE; FORMULATION; SYMPTOMS C1 NIMH, NIH, Mood & Anxiety Disorders Res Programs, Bethesda, MD 20892 USA. Innsbruck Univ Clin, Dept Biol Psychiat, Innsbruck, Austria. RP Neumeister, A (reprint author), NIMH, NIH, Mood & Anxiety Disorders Res Programs, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2001 VL 61 IS 15 BP 2229 EP 2230 DI 10.2165/00003495-200161150-00008 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 510PX UT WOS:000173217400008 ER PT J AU Reynolds, CF Alexopoulos, GS Katz, IR Lebowitz, BD AF Reynolds, CF Alexopoulos, GS Katz, IR Lebowitz, BD TI Chronic depression in the elderly - Approaches for prevention SO DRUGS & AGING LA English DT Article ID RECURRENT MAJOR DEPRESSION; RANDOMIZED CONTROLLED TRIAL; GERIATRIC DEPRESSION; LATE-LIFE; INTERPERSONAL PSYCHOTHERAPY; NORTRIPTYLINE; OUTCOMES; RECOVERY; TERM; DISCONTINUATION AB Depression in old age frequently follows a chronic and/or relapsing course, related to medical comorbidity, cognitive impairment and depletion of psychosocial resources. As endorsed by the US National Institutes of Health (NIH) Consensus Development Conference on the Diagnosis and Treatment of Late Life Depression, a major goal of treatment is to prevent relapse, recurrence and chronicity. We believe that most, if not all, elderly patients with major depressive episodes are appropriate candidates for maintenance therapy, because of the vulnerability to relapse and recurrence and because of the favourable benefit to risk ratio of available treatments. Antidepressant pharmacotherapy is the mainstay of this therapeutic goal, but psychosocial approaches (especially interpersonal psychotherapy) have also been shown to contribute significantly to prevention of a chronic depressive illness and to prevention of the disability that attends depression. Studies published to date have established the long term or maintenance efficacy of the tricyclic antidepressant nortriptyline. Current, ongoing studies are addressing the maintenance efficacy of paroxetine and citalopram to prolong recovery in depression associated with old age. These studies are focusing particularly on patients aged 70 years and above, who are at high risk of recurrence, and on patients in primary care settings, where under-recognition and under-treatment of depression in the elderly have been costly from a public health perspective in terms of increased medical utilisation, burden to patients and families, and high rates of suicide. Depression in old age is a major contributor to the global burden of illness-related disability, but it is extremely treatable if appropriate pharmacotherapy is prescribed and accepted by patients and their caregivers. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. Cornell Univ, Coll Med, White Plains, NY 10605 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NIMH, Bethesda, MD 20892 USA. RP Reynolds, CF (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Room 1135E,3811 OHara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [MH59380, P30 MH 52129, P30 MH 49762, P30 MH52247, MH59381, MH59366] NR 43 TC 32 Z9 32 U1 1 U2 4 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2001 VL 18 IS 7 BP 507 EP 514 DI 10.2165/00002512-200118070-00004 PG 8 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 454ZD UT WOS:000170000900004 PM 11482744 ER PT S AU Gronenborn, AM AF Gronenborn, AM BE Jardetzky, O Finucane, MD TI Exploiting magnetic field induced alignment - Residual dipolar couplings for NMR structure determination SO DYNAMICS, STRUCTURE AND FUNCTION OF BIOLOGICAL MACROMOLECULES SE NATO SCIENCE SERIES, SERIES A: LIFE SCIENCE LA English DT Proceedings Paper CT 4th NATO Advanced-Study-Institute on Dynamics, Structure and Function of Biological Macromolecules CY MAY 25-JUN 05, 1999 CL ERICE, ITALY SP NATO, Int Sch Struct Biol & Magnet Resonance ID LIQUID-CRYSTALLINE MEDIUM; TOBACCO MOSAIC-VIRUS; X-RAY-DIFFRACTION; ORIENTED MACROMOLECULES; STRUCTURE REFINEMENT; FILAMENTOUS PHAGE; HUMAN UBIQUITIN; NEMATIC PHASE; PROTEINS; RESOLUTION AB Residual dipolar couplings arise from small degrees of alignment of molecules in a magnetic field. Media employed for imparting alignment onto biomolecules lacking sufficient magnetic susceptibility anisotropies themselves comprise dilute aqueous phospholipid bicelles, colloidal suspensions of rod-shaped viruses and lamellar phases of quasiternary surfactant systems. The stability of these liquid crystalline phases with respect to temperature range, pH variation and time varies and is critically dependent on sample composition and experimental conditions. The magnitude of the residual dipolar couplings depends upon the degree of ordering and allows the determination of the corresponding internuclear vectors with respect to the molecule's alignment frame. Inclusion of dipolar constraints into NMR structure calculations leads to improved accuracy of the resulting structures, especially in cases where the information content provided by traditional NOE constraints is limited. C1 NIH, NIDDK, Phys Chem Lab, Bethesda, MD 20892 USA. RP Gronenborn, AM (reprint author), NIH, NIDDK, Phys Chem Lab, Bldg 5, Bethesda, MD 20892 USA. NR 51 TC 1 Z9 1 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-6686 BN 1-58603-032-9 J9 NATO SCI S A LIF SCI PY 2001 VL 315 BP 107 EP 116 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BS59G UT WOS:000170487100008 ER PT S AU Leapman, RD AF Leapman, RD BE Aindow, M Kiely, CJ TI Analysis of biological structures by EELS and energy filtering SO ELECTRON MICROSCOPY AND ANALYSIS 2001 SE INSTITUTE OF PHYSICS CONFERENCE SERIES LA English DT Article; Proceedings Paper CT Conference of the Electron-Microscopy-and Analysis-Group CY SEP 05-07, 2001 CL UNIV DUNDEE, DUNDEE, SCOTLAND SP Electron Microscopy & Anal Grp, Royal Microscop Soc, Inst Mat HO UNIV DUNDEE ID TRANSMISSION ELECTRON-MICROSCOPY; POSTCOLUMN IMAGING FILTER; CRYOSECTIONED CELLS; LOSS SPECTROSCOPY; SYSTEM AB Electron energy-loss spectroscopy (EELS) in the scanning transmission electron microscope (STEM) and in the energy-filtering transmission electron microscope (EFTEM) each provides important compositional information about biological structures. With recent improvements in instrumentation, detection limits are approaching those predicted by theory. In some applications, single atom detection is feasible for core-loss elemental maps acquired in a STEM equipped with field-emission source, parallel-detection EELS and spectrum-imaging capability. Spectrum-imaging in the EFTEM provides a complementary, quantitative technique for mapping elements that occur at relatively high concentrations over larger specimen areas. C1 NIH, Bethesda, MD 20892 USA. RP Leapman, RD (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 25 TC 0 Z9 0 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0951-3248 BN 0-7503-0812-5 J9 INST PHYS CONF SER PY 2001 IS 168 BP 9 EP 14 PG 6 WC Instruments & Instrumentation; Materials Science, Characterization & Testing; Microscopy; Physics, Multidisciplinary SC Instruments & Instrumentation; Materials Science; Microscopy; Physics GA BU50T UT WOS:000176200500002 ER PT J AU Stastna, M Radko, SP Chrambach, A AF Stastna, M Radko, SP Chrambach, A TI Discrimination between peak spreading in capillary zone electrophoresis of proteins due to interaction with the capillary wall and due to protein microheterogeneity SO ELECTROPHORESIS LA English DT Article DE capillary electrophoresis; dispersion mechanism; wall interaction versus microheterogeneity; proteins ID HIGH-PERFORMANCE ELECTROPHORESIS; ADSORPTION; POLYMER; LENGTH AB Our study attempts to find an approach to distinguishing between the contribution to peak spreading in capillary zone electrophoresis (CZE) due to protein microheterogeneity and that due to interaction with the capillary wall, by analyzing correlations between observed peak spreading and peak asymmetry. The peak asymmetry was measured as In[(t(m)-t(1))/(t(2)-t(m))] where t(m), t(1), and t(2) are migration times at the mode of the peak and at the intersection of the peak width at half-height with the ascending and descending limbs, respectively. Two isoforms of recombinant green fluorescent protein (GFP-1 and GFP-2, 27 kDa molecular mass), glucose-6-phosphate dehydrogenase (GPD, 104 kDa), and the naturally fluorescent protein R-phycoerythrin (PHYCO, 240 kDa) were subjected to CZE in polyacrylamide-coated fused-silica capillaries of 50 and 100 mum diameters under varying conditions of protein concentration, field strength, and the initial zone length. Under conditions such that contributions to peak spreading from axial diffusion, thermal effects, and electrophoretic dispersion are negligible, the analysis of the interrelations between peak width and peak asymmetry was found to allow a conclusion as to the cause of peak spreading in CZE of protein. It appears that the peak width of GFP-2 originates mostly in protein microheterogeneity while that of GFP-1 is due to protein-capillary wall interactions. For PHYCO, both microheterogeneity and protein-capillary wall interactions contribute to peak spreading. GPD exhibits relatively little microheterogeneity or interaction with capillary walls. Thus, its peak width appears to be mostly affected by an extracolumn source of spreading such as the initial zone length. C1 NICHHD, NIH, Lab Cellular & Mol Biophys, Macromol Anal Sect, Bethesda, MD 20892 USA. RP Chrambach, A (reprint author), NICHHD, NIH, Lab Cellular & Mol Biophys, Macromol Anal Sect, Bldg 10,Rm 9D50, Bethesda, MD 20892 USA. RI Stastna, Miroslava/G-9266-2014 NR 18 TC 13 Z9 13 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JAN PY 2001 VL 22 IS 1 BP 66 EP 70 DI 10.1002/1522-2683(200101)22:1<66::AID-ELPS66>3.0.CO;2-9 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 390EJ UT WOS:000166282500013 PM 11197181 ER PT S AU Podgornik, R AF Podgornik, R BE Holm, C Kekicheff, P Podgornik, R TI Interactions and conformational fluctuations in macromolecular arrays SO ELECTROSTATIC EFFECTS IN SOFT MATTER AND BIOPHYSICS SE NATO Science Series II-Mathematics Physics and Chemistry LA English DT Proceedings Paper CT Conference of the NATO Advanced Research Workshop on Electrostatic Effects in Soft Matter and Biophysics CY OCT 01-13, 2000 CL LES HOUCHES, FRANCE SP NATO ID CHARGED LAMELLAR PHASES; ENHANCED ELECTROSTATIC FORCES; DER-WAALS INTERACTION; FLUID MEMBRANES; DOUBLE-LAYER; PHOSPHOLIPID-BILAYERS; CURVATURE ELASTICITY; OSMOTIC-PRESSURE; HYDRATION FORCES; LIPID-BILAYERS C1 NICHHD, LPSB, NIH, Bethesda, MD 20892 USA. RP NICHHD, LPSB, NIH, Bethesda, MD 20892 USA. EM rudolf.podgornik@fiz.uni-lj.si NR 57 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1568-2609 BN 1-4020-0197-5; 1-4020-0196-7 J9 NATO SCI SER II-MATH PY 2001 VL 46 BP 409 EP 439 PG 31 WC Biochemistry & Molecular Biology; Biophysics; Physics, Atomic, Molecular & Chemical SC Biochemistry & Molecular Biology; Biophysics; Physics GA BU46M UT WOS:000176064100012 ER PT J AU Brown, P Will, RG Bradley, R Asher, DM Detwiler, L AF Brown, P Will, RG Bradley, R Asher, DM Detwiler, L TI Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease: Background, evolution, and current concerns SO EMERGING INFECTIOUS DISEASES LA English DT Article ID GREAT-BRITAIN; MOUSE SCRAPIE; HUMAN HEALTH; TRANSMISSION; HUMANS; MICE; BSE; CJD; UK; EPIDEMIC AB The epidemic of bovine spongiform encephalopathy (BSE) in the United Kingdom, which began in 1986 and has affected nearly 200,000 cattle, is waning to a conclusion, but leaves in its wake an outbreak of human Creutzfeldt-Jakob disease, most probably resulting from the consumption of beef products contaminated by central nervous system tissue. Although averaging only 10-15 cases a year since its first appearance in 1994, its future magnitude and geographic distribution (in countries that have imported infected British cattle or cattle products, or have endogenous BSE) cannot yet be predicted. The possibility that large numbers of apparently healthy persons might be incubating the disease raises concerns about iatrogenic transmissions through instrumentation (surgery and medical diagnostic procedures) and blood and organ donations. Government agencies in many countries continue to implement new measures to minimize this risk. C1 NINDS, NIH, Cent Nervous Syst Studies Lab, Bethesda, MD 20892 USA. Western Gen Hosp, Natl Creutzfeldt Jakob Dis Surveillance Unit, Edinburgh EH4 2XU, Midlothian, Scotland. Cent Vet Lab, Addlestone, Surrey, England. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. USDA, Anim & Plant Hlth Inspect Serv, Robbinsville, NJ USA. RP Brown, P (reprint author), NINDS, NIH, Cent Nervous Syst Studies Lab, Bldg 36,Room 4A-05,36 Convent Dr,MSC 4122, Bethesda, MD 20892 USA. EM brownp@ninds.nih.gov NR 49 TC 138 Z9 150 U1 1 U2 14 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JAN-FEB PY 2001 VL 7 IS 1 BP 6 EP 16 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 403EG UT WOS:000167029200002 PM 11266289 ER PT J AU Li, J Collins, WE Wirtz, RA Rathore, D Lal, A McCutchan, TF AF Li, J Collins, WE Wirtz, RA Rathore, D Lal, A McCutchan, TF TI Geographic subdivision of the range of the malaria parasite Plasmodium vivax SO EMERGING INFECTIOUS DISEASES LA English DT Article ID CIRCUMSPOROZOITE PROTEIN GENE; IDENTIFICATION; BRASILIANUM; FALCIPARUM; INFECTION; EVOLUTION; MOSQUITOS; RNA AB We examined geographically distinct isolates of Plasmodium vivax and categorized them according to developmental success in Anopheles albimanus. We found that parasites from Central America and Colombia form a group distinct from those of Asia. New World isolates have a distinct chromosomal translocation and an episomal variation in the open reading frame (ORF) 470 DNA sequence that distinguishes them from the other isolates tested. Old World types of P. vivax were introduced into the Americas, and a remnant of this lineage remains in P. simium. it is indistinguishable from Old World P. vivax to the extent determinable by using our encoded markers and the examination of its developmental pattern in mosquitoes. The cohesive characteristics that separate types of P. vivax are predictors of range and potential for transmission and hence require taxonomic distinction. C1 NIAID, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP McCutchan, TF (reprint author), NIAID, NIH, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA. NR 22 TC 55 Z9 58 U1 0 U2 1 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JAN-FEB PY 2001 VL 7 IS 1 BP 35 EP 42 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 403EG UT WOS:000167029200005 PM 11266292 ER PT J AU Grady, C Ramjee, G Pape, J Hofman, K Speers, M AF Grady, C Ramjee, G Pape, J Hofman, K Speers, M TI Ethical and legal issues in infectious disease research and control SO EMERGING INFECTIOUS DISEASES LA English DT Editorial Material C1 NIH, Fogarty Int Hlth Ctr, Bethesda, MD 20892 USA. MRC, Durban, South Africa. Grp Haitien Etud Sarcome Kaposi & Infect Opportun, Port Au Prince, Haiti. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Hofman, K (reprint author), NIH, Fogarty Int Hlth Ctr, 16 Ctr Dr,Bldg 16, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PY 2001 VL 7 IS 3 SU S BP 534 EP 534 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 459BW UT WOS:000170230800013 PM 11485651 ER PT J AU Breman, J LeDuc, J AF Breman, J LeDuc, J TI International partnerships in infectious diseases research, training, and control SO EMERGING INFECTIOUS DISEASES LA English DT Editorial Material C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Breman, J (reprint author), NIH, Fogarty Int Ctr, Bldg 31,Room B2C39,31 Ctr Dr,MSC 2220, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PY 2001 VL 7 IS 3 SU S BP 542 EP 543 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 459BW UT WOS:000170230800021 PM 11485659 ER PT J AU Hunter, PR Colford, JM LeChevallier, MW Binder, S Berger, PS AF Hunter, PR Colford, JM LeChevallier, MW Binder, S Berger, PS TI Waterborne diseases SO EMERGING INFECTIOUS DISEASES LA English DT Editorial Material C1 Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. WHO, CH-1211 Geneva, Switzerland. NIH, Bethesda, MD 20892 USA. US EPA, Washington, DC 20460 USA. RP Binder, S (reprint author), Ctr Dis Control & Prevent, 4770 Buford Highway NE,Mailstop K02, Atlanta, GA 30341 USA. RI Hunter, Paul/A-7172-2008 OI Hunter, Paul/0000-0002-5608-6144 NR 0 TC 16 Z9 18 U1 0 U2 4 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PY 2001 VL 7 IS 3 SU S BP 544 EP 545 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 459BW UT WOS:000170230800023 PM 11485661 ER PT J AU Teklehaimanot, A Keusch, G Binder, S AF Teklehaimanot, A Keusch, G Binder, S TI Malaria SO EMERGING INFECTIOUS DISEASES LA English DT Editorial Material C1 Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. WHO, CH-1211 Geneva, Switzerland. NIH, Bethesda, MD 20892 USA. RP Binder, S (reprint author), Ctr Dis Control & Prevent, 4770 Buford Highway NE,Mailstop K02, Atlanta, GA 30341 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PY 2001 VL 7 IS 3 SU S BP 546 EP 547 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 459BW UT WOS:000170230800025 PM 11485663 ER PT J AU Chamberland, ME Alter, HJ Busch, MP Nemo, G Ricketts, M AF Chamberland, ME Alter, HJ Busch, MP Nemo, G Ricketts, M TI Emerging infectious disease issues in blood safety SO EMERGING INFECTIOUS DISEASES LA English DT Editorial Material AB Improvements in donor screening and testing and viral inactivation of plasma derivatives together have resulted in substantial declines in transfusion-transmitted infections over the last two decades. Most recently, nucleic acid testing techniques have been developed to screen blood and plasma donations for evidence of very recent viral infections that could be missed by conventional serologic tests. Nonetheless, the blood supply remains vulnerable to new and reemerging infections. In recent years, numerous infectious agents found worldwide have been identified as potential threats to the blood supply. Several newly discovered hepatitis viruses and agents of transmissible spongiform encephalopathies present unique challenges in assessing possible risks they may pose to the safety of blood and plasma products. C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NIH, Bethesda, MD 20892 USA. Blood Ctr Pacific, San Francisco, CA USA. WHO, CH-1211 Geneva, Switzerland. RP Chamberland, ME (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd,Mailstop A30, Atlanta, GA 30333 USA. NR 0 TC 34 Z9 39 U1 1 U2 6 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PY 2001 VL 7 IS 3 SU S BP 552 EP 553 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 459BW UT WOS:000170230800031 PM 11485669 ER PT J AU Brown, P AF Brown, P TI Afterthoughts about bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease SO EMERGING INFECTIOUS DISEASES LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Brown, P (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PY 2001 VL 7 IS 3 SU S BP 598 EP 600 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 459BW UT WOS:000170230800044 PM 11485682 ER PT J AU Dhanvantari, S Izzo, A Jansen, E Brubaker, PL AF Dhanvantari, S Izzo, A Jansen, E Brubaker, PL TI Coregulation of glucagon-like peptide-1 synthesis with proglucagon and prohormone convertase 1 gene expression in enteroendocrine GLUTag cells SO ENDOCRINOLOGY LA English DT Article ID CAMP RESPONSE ELEMENTS; PROINSULIN BIOSYNTHESIS; PROPROTEIN CONVERTASES; DIABETES-MELLITUS; BETA-TC3 CELLS; RAT PITUITARY; PC2; GLUCOSE; LINE; RNA AB The insulinotropic hormone glucagon-like peptide-1 (GLP-1) is synthesized in the intestinal L cell by prohormone convertase 1 (PC1)-mediated posttranslational processing of proglucagon. Previous studies have demonstrated that proglucagon gene transcription in the L cell is stimulated by the protein kinase A (PKA) pathway through a cAMP response element (CRE). Because the PC1 gene contains two functional CREs, the present studies were conducted to investigate whether the PC1 and proglucagon genes are coregulated by PKA, and to elucidate the temporal relationship(s) of PC1 and proglucagon gene expression with production of GLP-1, in the intestinal cell. The GLUTag enteroendocrine cell line, which is known to express the proglucagon gene and to synthesize and secrete GLP-1, was used as a model. Proglucagon and PC1 messenger RNA transcript levels were both increased after 12 h (but not 24 h) of treatment of GLUTag cells with forskolin/isobutylmethylxanthine (IBMX), by 2.7 +/- 0.3- and 2.4 +/- 0.8-fold, respectively, compared with controls (P < 0.01-0.001). Activation of PKA resulted in a 2.1 +/- 0.1-fold increase in PC1 reporter construct expression (P < 0.001) at 12 h, which was dependent on the presence of the CRE, and a 13- to 24-fold increment in PC1 protein levels (P < 0.01) at 12 and 24 h. Similarly, forskolin/IBMX increased secretion of GLP-1, by 1.8 +/- 0.2- and 2.2 +/- 0.6-fold at 12 and 24 h, respectively (P < 0.05-0.01). Although the cell content of GLP-1 was diminished after 12 h of treatment (P < 0.001), GLP-1 levels increased back to control values after 24 h of forskolin/IBMX treatment (P < 0.01 vs. 12-h levels). Thus, PICA-induced secretion of GLP-1 from the L cell is followed by restoration of the cellular peptide levels through a PKA-mediated, CRE-dependent up-regulation of proglucagon and PC1 gene expression. C1 Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada. NICHHD, Dev Neurobiol Lab, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. Katholieke Univ Leuven, Ctr Human Genet, Mol Oncol Lab, Louvain, Belgium. Flanders Interuniv Inst Biotechnol, Louvain, Belgium. RP Brubaker, PL (reprint author), Univ Toronto, Dept Physiol, Room 3366,Med Sci Bldg, Toronto, ON M5S 1A8, Canada. RI Dhanvantari, Savita/B-5362-2015 NR 37 TC 17 Z9 17 U1 0 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2001 VL 142 IS 1 BP 37 EP 42 DI 10.1210/en.142.1.37 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 390QW UT WOS:000166308700006 PM 11145564 ER PT J AU Mann, CL Cidlowski, JA AF Mann, CL Cidlowski, JA TI Glucocorticoids regulate plasma membrane potential during rat thymocyte apoptosis in vivo and in vitro SO ENDOCRINOLOGY LA English DT Article ID SENSITIVE ION CHANNELS; DEOXYRIBONUCLEIC-ACID; POTASSIUM CHANNELS; FLOW-CYTOMETRY; ACTIVATION; LYMPHOCYTES; CELLS; RECEPTOR; RECOGNITION; DEGRADATION AB Glucocorticoids induce a series of profound biochemical changes in thymocytes that initiate apoptosis; however, the pathways beyond receptor transactivation that lead to this form of cell death are not fully understood. In this study, we report a novel site of action for glucocorticoids at the site of the plasma membrane. Specifically, we find that glucocorticoids induce the loss of plasma membrane potential both in vivo and in vitro. The glucocorticoid-induced loss of plasma membrane potential in cultured primary isolated rat thymocytes was both dose and time dependent. Other steroid hormones, including progesterone, estrogen, and testosterone, fail to alter the depolarization state of the thymocyte plasma membrane. Interestingly, other nonsteroid stimuli that also activate apoptosis in thymocytes also lead to cellular depolarization. In contrast, HeLa cells, which contain functional glucocorticoid receptors but do not die in response to hormone, do not alter their plasma membrane potential in response to glucocorticoids, indicating a strong association between depolarization and apoptosis. Furthermore, the ability of glucocorticoids to depolarize the plasma membrane of thymocytes required the interaction of glucocorticoids with their cognate receptor, because RU486 failed to depolarize thymocytes and antagonized the effect of glucocorticoids. Finally, experiments using inhibitors of transcription and translation indicated that the loss of plasma membrane potential in thymocytes following glucocorticoid treatment required de novo gene expression. The results of these studies establish that the loss of plasma membrane potential is an early important feature of glucocorticoid-induced apoptosis of thymocytes. C1 Univ N Carolina, NIEHS, Mol Endocrinol Grp, Lab Signal Transduct,NIH,Curriculum Toxicol, Chapel Hill, NC 27599 USA. RP Cidlowski, JA (reprint author), POB 12233 MD F3-07,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 42 TC 42 Z9 44 U1 1 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2001 VL 142 IS 1 BP 421 EP 429 DI 10.1210/en.142.1.421 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 390QW UT WOS:000166308700048 PM 11145606 ER PT J AU De Luca, F Barnes, KM Uyeda, JA De-Levi, S Abad, V Palese, T Mericq, V Baron, J AF De Luca, F Barnes, KM Uyeda, JA De-Levi, S Abad, V Palese, T Mericq, V Baron, J TI Regulation of growth plate chondrogenesis by bone morphogenetic protein-2 SO ENDOCRINOLOGY LA English DT Article ID TGF-BETA-SUPERFAMILY; CARTILAGE DIFFERENTIATION; ASCORBIC-ACID; FACTOR-I; CHONDROCYTES; EXPRESSION; BMP-2; CELLS; NOGGIN; MEMBER AB Bone morphogenetic proteins (BMPs) regulate embryonic skeletal development. We hypothesized that BMP-2, which is expressed in the growth plate, also regulates growth plate chondrogenesis and longitudinal bone growth. To test this hypothesis, fetal rat metatarsal hones were cultured for 3 days in the presence of recombinant human BMP-2. The addition of BMP-2 caused a concentration-dependent acceleration of metatarsal longitudinal growth. As the rate of longitudinal bone growth depends primarily on the rate of growth plate chondrogenesis, we studied each of its three major components. BMP-2 stimulated chondrocyte proliferation in the epiphyseal zone of the growth plate, as assessed by [H-3]thymidine incorporation. BMP-2 also caused an increase in chondrocyte hypertrophy, as assessed by quantitative histology and enzyme histochemistry. A stimulatory effect on cartilage matrix synthesis, assessed by (SO4)-S-35 incorporation into glycosaminoglycans, was produced only by the highest concentration of BMP-2. These BMP-2-mediated stimulatory effects were reversed by recombinant human Noggin, a glycoprotein that blocks BMP-2 action. In the absence of exogenous BMP-2, Noggin inhibited metatarsal longitudinal growth, chondrocyte proliferation, and chondrocyte hypertrophy, which suggests that endogenous BMPs stimulate longitudinal bone growth and chondrogenesis. We conclude that BMP-2 accelerates longitudinal bone growth by stimulating growth plate chondrocyte proliferation and chondrocyte hypertrophy. C1 Univ Maryland, Sch Med, Dept Pediat, Div Pediat Endocrinol, Baltimore, MD 21201 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP De Luca, F (reprint author), Univ Maryland, Sch Med, Dept Pediat, Div Pediat Endocrinol, 22 S Greene St,Room N5E13, Baltimore, MD 21201 USA. RI Mericq, Veronica/F-3927-2010 NR 42 TC 106 Z9 108 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2001 VL 142 IS 1 BP 430 EP 436 DI 10.1210/en.142.1.430 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 390QW UT WOS:000166308700049 PM 28201304 ER PT J AU Bohr, VA Pinto, NS Nyaga, SG Dianov, G Kraemer, K Seidman, MM Brash, RM AF Bohr, VA Pinto, NS Nyaga, SG Dianov, G Kraemer, K Seidman, MM Brash, RM TI DNA repair and mutagenesis in Werner syndrome SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE mutagenesis; Werner syndrome; base excision repair; nucleotide excision repair; whole cell extracts; DNA repair ID RNA-POLYMERASE-II; SYNDROME PROTEIN; MITOCHONDRIAL-DNA; OXIDATIVE DAMAGE; ESCHERICHIA-COLI; MAMMALIAN-CELLS; SYNDROME GENE; WRN PROTEIN; HELICASE; TRANSCRIPTION AB Werner syndrome (WS) is the hallmark premature aging syndrome in which the patients appear much older than their actual chronological age. The disorder is associated with significantly increased genome instability and with transcriptional deficiencies. There has been some uncertainty about whether WS cells are defective in DNA repair. We thus examined repair in vitro in nuclear and mitochondria( DNA. Whereas cellular studies so far do not show significant DNA repair deficiencies, biochemical studies with the Werner protein clearly indicate that it plays a role in DNA repair. Published 2001 Wiley-Liss, Inc. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. MRC, Radiat & Genome Stabil Unit, Harwell, Oxon, England. NCI, Basic Res Lab, NIH, Bethesda, MD USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Souza-Pinto, Nadja/C-3462-2013 OI Souza-Pinto, Nadja/0000-0003-4206-964X NR 40 TC 24 Z9 25 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2001 VL 38 IS 2-3 BP 227 EP 234 DI 10.1002/em.1076 PG 8 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 489XG UT WOS:000172017400021 PM 11746759 ER PT J AU Whittaker, P Seifried, HE San, RHC Clarke, JJ Dunkel, VC AF Whittaker, P Seifried, HE San, RHC Clarke, JJ Dunkel, VC TI Genotoxicity of iron chelators in L5178Y mouse lymphoma cells SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE iron chelators; iron toxicity; thalassemia; mutagenicity; mouse lymphoma assay ID DEXRAZOXANE ICRF-187; CLINICAL USE; THALASSEMIA; TOXICITY; DEFERIPRONE; MODULATION; MUTATIONS; EFFICACY; THERAPY; LOCUS AB To further study the mechanism of observed iron mutagenicity and cellular toxicity, a number of different iron chelators were evaluated to select a compound that was not mutagenic and had limited toxicity to mouse lymphoma cells. A series of iron chelators including those used clinically, those under development for clinical applications, and those used in nonclinical applications were evaluated. The mutagenic activity of the iron chelators was assessed in L5178Y mouse lymphoma cells. Eight of the 12 iron chelators that were tested induced mutagenic responses both with and without The addition of S9. Among those chelators used clinically or developed for clinical use, the only compound that did not induce a mutagenic response was the starch deferoxamine conjugate. In contrast, deferoxamine mesylate showed the highest toxicity in this group of chemicals and the concentrations leading to toxicity and mutagenicity between the activated and nonactivated assays were not significantly different. The other three chelators that were not mutagenic were Na(2)EDTA, phyfic acid, and ferrozine, Environ. Mol. Mutagen. 38:347-356, 2001. Published 2001 Wiley-Liss, Inc. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. BioReliance Corp, Rockville, MD USA. NCI, NIH, Bethesda, MD 20892 USA. RP Whittaker, P (reprint author), US FDA HFS236, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. FU NCI NIH HHS [N01-CB-87106] NR 32 TC 10 Z9 10 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2001 VL 38 IS 4 BP 347 EP 356 DI 10.1002/em.10033 PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 510QJ UT WOS:000173218500011 PM 11774367 ER PT J AU Bonassi, S Fenech, M Lando, C Lin, YP Ceppi, M Chang, WP Holland, N Kirsch-Volders, M Zeiger, E Ban, SY Barale, R Bigatti, MP Bolognesi, C Jia, C Di Giorgio, M Ferguson, LR Fucic, A Lima, OG Hrelia, P Krishnaja, AP Lee, TK Migliore, L Mikhalevich, L Mirkova, E Mosesso, P Muller, WU Odagiri, Y Scarfi, MR Szabova, E Vorobtsova, I Vral, A Zijno, A AF Bonassi, S Fenech, M Lando, C Lin, YP Ceppi, M Chang, WP Holland, N Kirsch-Volders, M Zeiger, E Ban, SY Barale, R Bigatti, MP Bolognesi, C Jia, C Di Giorgio, M Ferguson, LR Fucic, A Lima, OG Hrelia, P Krishnaja, AP Lee, TK Migliore, L Mikhalevich, L Mirkova, E Mosesso, P Muller, WU Odagiri, Y Scarfi, MR Szabova, E Vorobtsova, I Vral, A Zijno, A TI HUman MicroNucleus Project: International database comparison for results with the cytokinesis-block micronucleus assay in human lymphocytes: I. Effect of laboratory protocol, scoring criteria, and host factors on the frequency of micronuclei SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE cytokinesis-block micronucleus assay; peripheral blood lymphocytes; pooled re-analysis; biomarkers; DNA damage ID PERIPHERAL-BLOOD LYMPHOCYTES; SISTER-CHROMATID EXCHANGE; VINYL-CHLORIDE MONOMER; CULTURED HUMAN-LYMPHOCYTES; C-INDUCED MICRONUCLEI; PREDICT HUMAN CANCER; AGE-RELATED INCREASE; CHROMOSOME-ABERRATIONS; HUMAN-POPULATIONS; GENETIC-DAMAGE AB Micronucleus (MN) expression in peripheral blood lympbocytes is well established as a standard method for monitoring chromosome damage in human populations. The First results of an analysis of pooled data from laboratories using the cytokinesis-block micronucleus (CBMN) assay and participating in the HUMN (HUman MicroNucleus project) international collaborative study are presented. The effects of laboratory protocol, scoring criteria, and host factors on baseline micronucleated binucleate cell (MNC) frequency are evaluated, and a reference range of "normal" values against which future studies may be compared is provided. Primary data From historical records were submitted by 25 laboratories distributed in 16 countries. This resulted in a database of nearly 7000 subjects. Potentially significant differences were present in the methods used by participating laboratories, such as in the type of culture medium, the concentration of cytochalasin-B, the percentage of fetal calf serum, and in the culture method. Differences in criteria For scoring micronuclei were also evident. The overall median MNC frequency in nonexposed (i.e., normal) subjects was 6.5 parts per thousand and the interquartile range was between 3 and 12 parts per thousand. An increase in MNC frequency with age was evident in all but two laboratories. The effect of gender, although not so evident in all databases, was also present, with females having a 19% higher lever of MNC frequency (95% confidence interval: 14-24%). Statistical analyses were performed using random-effects models For correlated data. Our best model, which included exposure to genotoxic factors, host factors, methods, and scoring criteria, explained 75% of the total variance, with the largest contribution attributable to laboratory methods. (C) 2001 Wiley-Liss, Inc. C1 Ist Nazl Ric Canc, Dept Environm Epidemiol, I-16132 Genoa, Italy. CSIRO, Adelaide, SA, Australia. Natl Yang Ming Univ, Sch Med, Inst Environm Hlth Sci, Taipei 112, Taiwan. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Free Univ Brussels, Lab Cell Genet, Brussels, Belgium. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Radiat Effects Res Fdn, Dept Radiobiol, Hiroshima, Japan. Univ Pisa, Dipartimento Sci Uomo & Ambiente, Pisa, Italy. Univ Turin, Dipartimento Biol Anim, I-10123 Turin, Italy. Ist Nazl Ric Canc, Toxicol Evaluat Unit, I-16132 Genoa, Italy. Third Mil Med Univ, Mol Toxicol Lab, Chongqing, Peoples R China. Autoridad Regulatoria Nucl, Lab Dosimetria Biol, Buenos Aires, DF, Argentina. Auckland Canc Soc, Res Ctr, Auckland, New Zealand. Inst Med Res & Occupat Hlth, Zagreb, Croatia. Ctr Protecc & Higiene Radiaciones, Havana, Cuba. Univ Bologna, Dept Pharmacol, Bologna, Italy. Bhabha Atom Res Ctr, Div Cell Biol, Bombay 400085, Maharashtra, India. E Carolina Univ, Sch Med, Leo Jenkins Canc Ctr, Dept Radiat Oncol, Greenville, NC USA. Belarus Acad Sci, Inst Cytol & Genet, Minsk, Byelarus. Natl Ctr Hyg Med Ecol & Nutr, Sofia, Bulgaria. Univ Tuscia, Dipartimento Agrobiol & Agrochim, I-01100 Viterbo, Italy. Univ Essen Gesamthsch Klinikum, Inst Med Strahlenbiol, D-4300 Essen, Germany. Yamanashi Prefectural Coll Nursing, Div Human & Hlth Sci, Kofu, Yamanashi, Japan. CNR, Ist Ric Elettromagnetismo Componendi Elettron, I-80125 Naples, Italy. Inst Prevent & Clin Med, Bratislava, Slovakia. Cent Res Inst Roentgenol & Radiol, St Petersburg, Russia. Univ Ghent, Dept Anat Histol & Embryol, B-9000 Ghent, Belgium. Ist Super Sanita, Comparat Toxicol & Ecotoxicol Lab, I-00161 Rome, Italy. RP Bonassi, S (reprint author), Ist Nazl Ric Canc, Dept Environm Epidemiol, 10 Largo R Benzi, I-16132 Genoa, Italy. EM bonassi@hp380.ist.unige.it RI LEE, Tung-Kwang/A-4821-2008; Ferguson, Lynnette/F-5989-2011; Zijno, Andrea/H-9562-2014; OI Mosesso, Pasquale/0000-0001-5648-1366; BARALE, Roberto/0000-0003-4161-2241; bonassi, stefano/0000-0003-3833-6717 NR 94 TC 285 Z9 296 U1 0 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2001 VL 37 IS 1 BP 31 EP 45 PG 15 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 400AU UT WOS:000166847100005 PM 11170240 ER PT J AU Tennant, R Haseman, J Stoll, RE AF Tennant, R Haseman, J Stoll, RE TI Transgenic assays and the identification of carcinogens SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Letter ID LONG-TERM; CHEMICALS; MICE C1 NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Boehringer Ingelheim Pharmaceut Inc, Toxicol & Safety Assessment, Ridgefield, CT 06877 USA. RP Tennant, R (reprint author), NIEHS, Lab Environm Carcinogenesis & Mutagenesis, POB 12233, Res Triangle Pk, NC 27709 USA. NR 14 TC 3 Z9 3 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2001 VL 37 IS 1 BP 86 EP 88 DI 10.1002/1098-2280(2001)37:1<86::AID-EM1010>3.0.CO;2-G PG 3 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 400AU UT WOS:000166847100011 PM 11170246 ER PT J AU Johnson, FR AF Johnson, FR TI Response to Tennant et al.: Attempts to replace the NTP rodent bioassay with transgenic alternatives are unlikely to succeed SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Letter C1 NIEHS, Environm Toxicol Program, Toxicol Operat Branch, Res Triangle Pk, NC 27709 USA. RP Johnson, FR (reprint author), NIEHS, Environm Toxicol Program, Toxicol Operat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. NR 11 TC 10 Z9 10 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2001 VL 37 IS 1 BP 89 EP 92 DI 10.1002/1098-2280(2001)37:1<89::AID-EM1011>3.0.CO;2-4 PG 4 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 400AU UT WOS:000166847100012 ER PT J AU Li, YL Carty, MP Oakley, GG Seidman, MM Medvedovic, M Dixon, K AF Li, YL Carty, MP Oakley, GG Seidman, MM Medvedovic, M Dixon, K TI Expression of ATM in ataxia telangiectasia fibroblasts rescues defects in DNA double-strand break repair in nuclear extracts SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE double-strand break repair; nuclear extracts; ataxia telangiectasia; plasmid vector; deletion mutation ID NONPOLYPOSIS COLON-CANCER; POTENTIALLY LETHAL DAMAGE; CELL-LINE; XERODERMA-PIGMENTOSUM; GENE; RADIATION; HOMOLOG; PROTEIN; MUTATION; PRODUCT AB Ataxia telangiectasia (A-T) is cc human genetic disorder characterized by progressive cerebellar degeneration, hypersensitivity to ionizing radiation (IR), immunodeficiency, and high cancer risk. At the cellular level, IR sensitivity and increased frequency of spontaneous and IR-induced chromosomal breakage and rearrangements are the hallmarks of A-T. The ATM gene, mutated in this syndrome, has been cloned and codes for a protein sharing homology with DNA-PKcs, a protein kinase involved in DNA double-strand break (DSB) repair and DNA damage responses. The characteristics of the A-T cellular phenotypes and ATM gene suggest that ATM may play a role similar to that of DNA-PKcs in DSB repair and that there is a primary DNA repair defect in A-T cells. In the current study, the Function of ATM in DNA DSB repair was evaluated in an in vitro system using two plasmids, carrying either an EcoRI-induced DSB within the lacZ alpha gene or various endonuclease-induced DSB in the SupF suppressor tRNA gene. We Found that the DSB repair efficiency in A-T nuclear extracts was comparable to, if not higher than, that in normal nuclear extracts. However, the repair fidelity in A-T nuclear extracts was decreased when repairing DSB with short 5 ' and 3 ' overhangs (<4 base pairs (bp)) or blunt ends, but not 5 4-bp overhangs. Sequencing of the mutant plasmids revealed that deletions involving 1-6 nucleotide microhomologies were the major class of mutations in both A-T and normal extracts. However, the size of the deletions in plasmids from A-T nuclear extracts was larger than that from normal nuclear extracts. Expression of the ATM protein in A-T cells corrected the defect in DSB repair in A-T nuclear extracts. These results suggest that ATM ploys a role in maintaining genomic stability by preventing the repair of DSB from an error-prone pathway. Environ. (C) 2001 Wiley-Liss, Inc. C1 Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45267 USA. NIA, Genet Mol Lab, NIH, Baltimore, MD 21224 USA. RP Dixon, K (reprint author), Univ Cincinnati, Coll Med, Dept Environm Hlth, POB 670056, Cincinnati, OH 45267 USA. OI Oakley, Gregory/0000-0001-6207-0969 FU NIEHS NIH HHS [P30-ES06096]; NINDS NIH HHS [R01-NS34782] NR 49 TC 11 Z9 12 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2001 VL 37 IS 2 BP 128 EP 140 DI 10.1002/em.1020 PG 13 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 419NV UT WOS:000167955900004 PM 11246219 ER PT J AU Bordelon, NR Donnelly, KC George, SE AF Bordelon, NR Donnelly, KC George, SE TI Pentachlorophenol potentiates benzo[a]pyrene DNA adduct formation in adult but not infant B6C3F1 male mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE DNA adducts; age-dependent interactions; benzo[a]pyrene; pentachlorophenol; chemical mixtures ID LIVER DNA; DAMAGE; 8-HYDROXYDEOXYGUANOSINE; CARCINOGEN; 8-HYDROXYGUANINE; SENSITIVITY; ENHANCEMENT; METABOLITE; EXPRESSION; INDUCTION AB The objective of this study is to determine whether pentachlorophenol (PCP) alters benzo[a]pyrene (B[a]P)-induced DNA adduct Formation in infant and adult B6C3F1 male mice. Mice were exposed intraperitoneally to 55 mug B[a]P/g body weight (BW) alone and in combination with several doses of PCP in DMSO. The P-32-postlabeling assay was used to analyze For (+/-) anti-7,8diol-9,10-epoxideB[a] P-N(2)deoxyguanosine (BPDE-N(2)G) adducts formed in liver and lung DNA. Hepatic DNA also was analyzed For 8-hydroxy-2 ' -deoxyguanosine (8-OHdG) base damage in mice exposed to PCP. 8-OHdG was not detected at any dose of PCP in infant or adult mice. PCP exhibited an antagonistic effect on BPDE-N2G accumulation in infant mice exposed to B[a]P in combination with 50 mug PCP/g BW at both 12 and 24 hr. Comparatively, BPDE-N2G adducts were increased in adult mice exposed to binary mixtures at 24 hr in both hepatic and lung DNA (P < 0.05). Multiple comparison analysis between infant and adult mice revealed that adduct levels in infants exposed to B[a]P alone or in combination with PCP were not different from those observed in adult mice exposed to B[a]P. However, a significant increase in adducts was observed in adult mice exposed to a combination of B[a]P and PCP compared to that in all other treatment groups (P < 0.05). These results suggest that PCP alters the metabolism of B[a]P in both infant and adult mice through different mechanisms, and that infants are not susceptible to the potentiating effects of PCP observed in adult mice. Published 2001 Wiley-Liss, Inc.(dagger). C1 Texas A&M Univ, Dept Vet Anat & Publ Hlth, College Stn, TX USA. US EPA, Natl Hlth & Environm Effects Res Lab, Div Environm Carcinogenesis, Res Triangle Pk, NC USA. RP Bordelon, NR (reprint author), Natl Inst Environm Hlth Sci, 111 Alexander Dr,POB 12233,MD B3-07, Res Triangle Pk, NC 27711 USA. NR 37 TC 3 Z9 3 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2001 VL 37 IS 2 BP 164 EP 172 DI 10.1002/em.1024 PG 9 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 419NV UT WOS:000167955900008 PM 11246223 ER PT J AU Malling, HV Delongchamp, RR AF Malling, HV Delongchamp, RR TI Direct separation of in vivo and in vitro am3 revertants in transgenic mice carrying the phiX174 am3, cs70 vector SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE phiX174; transgenic; mice; revertants; ENU; spleen ID ETHYL-N-NITROSOUREA; SPONTANEOUS MUTATION; MUTAGENESIS; SINGLE; PHI-X174; BASEPAIR; SYSTEMS AB Target genes in most transgenic systems have higher spontaneous mutation frequencies than do endogenous mammalian genes. Spontaneous mutations in transgenes predominantly arise from three sources. (1) mutations fixed in the animals, (2) mutations arising from replication errors caused by damage to the DNA that may have occurred in vivo or in vitro and then was fixed during amplification of the vector in vitro, and (3) mutations arising during replication of non-revertant phages in non-permissive bacteria. An assay based on single bursts was developed to directly distinguish between the in vivo and in vitro origins of revertants. The sire of the aliquot is determined by mutant frequency and is adjusted so that ideally no more than 10 to 20% of the aliquots contain a bacterial cell transformed with a mutant phage. Mutations are detected as revertants of an amber mutation (am3) in phiX174 am3, cs70. The minimum burst size of non-revertant phiX174 am3, cs70 From splenic DNA on a permissive bacterial strain was larger than 30 plaque-forming units (pfu). Based on this observation, a burst size of 31 plaque-forming revertants was chosen as the minimum burst size of a fixed mutation. The single burst assay was tested on DNA from spleens of animals that were treated with 150 mg/kg 1-ethyl-1-nitrosurea. Only the fraction of aliquots with single bursts of revertants (> 30) increased in the treated animals compared to the controls. In contrast, there was no difference between treated and control animals For revertant frequencies calculated for burst sizes less than or equal to 30 pfu. Among the spontaneous mutations, only 30% were caused by mutations fixed in animals (i.e. burst size > 30 pfu). Total average revertant Frequency measured in DNA from treated animals was less than twofold more than the average spontaneous frequency (P = 0.048). When frequencies were based on burst sizes > 30, there was a 4.6-fold increase among treated animals compared with controls (P = 0.026). The single burst-assay resulted in a more sensitive test for mutagenicity because it eliminated noise from invitro mutations. Published 2001 Wiley-Liss, Inc.(+) C1 NIEHS, Mammalian Mutagenesis Grp, Environm Toxicol Program, Toxicol Lab, Res Triangle Pk, NC 27709 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Malling, HV (reprint author), NIEHS, Mammalian Mutagenesis Grp, Environm Toxicol Program, Toxicol Lab, MD F106,POB 12233, Res Triangle Pk, NC 27709 USA. NR 17 TC 12 Z9 12 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2001 VL 37 IS 4 BP 345 EP 355 DI 10.1002/em.1042 PG 11 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 450DR UT WOS:000169726700009 PM 11424185 ER PT J AU Delongchamp, RR Valentine, CR Malling, HV AF Delongchamp, RR Valentine, CR Malling, HV TI Estimation of the average burst size of Phi X174 am3, cs70 for use in mutation assays with transgenic mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE Phi X174 am3; cs70; transgenic mice; mutation assay; plaque count; burst size AB In mutation assays using transgenic mice, with recoverable vectors such as Phi X174 am3, cs70, mutations originate from two sources: (1) in vivo mutations, that is, mutations that were fixed in the mouse, or (2) ex vivo mutations, that is, mutations that were Fixed during recovery or plating. When a bacteriophage infects a bacterium, ii multiplies and bursts the cell, releasing a number of phages referred to as the burst size. Our method for distinguishing between in vivo mutations and ex vivo mutations estimates the average number of bursts, the denominator of in vivo mutant Frequencies, by dividing the total plaque-forming units (PFU) by the average number of phages in a burst. Herein, we outline a probability model relating observed plaque counts to the burst size and present the statistical method used to estimate the burst size. The average size of a single burst from nonrevertant phages was estimated in eight studies under the conditions of our mutation assay. The average burst size was stable across studies at 182.5 plaques per burst (standard error, 14.25). The probability that a burst is a specific size was approximated by a negative binomial distribution, which implies a Poisson-Pascal distribution for the observed plaque counts. The observed plaque counts were adequately Fit by this approximation. Published 2001 Wiley-Liss, Inc.(+) C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NIEHS, Mammalian Genet Grp, Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Delongchamp, RR (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, HFT-20,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 5 TC 7 Z9 7 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2001 VL 37 IS 4 BP 356 EP 360 DI 10.1002/em.1043.abs PG 5 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 450DR UT WOS:000169726700010 PM 11424186 ER PT S AU Couse, JF Korach, KS AF Couse, JF Korach, KS BE Mclachlan, JA Guillette, LJ Iguchi, T Toscano, WA TI Contrasting phenotypes in reproductive tissues of female estrogen receptor null mice SO ENVIRONMENTAL HORMONES: THE SCIENTIFIC BASIS OF ENDOCRINE DISRUPTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Environmental Hormones CY OCT 15-18, 2000 CL NEW ORLEANS, LOUISIANA SP Tulane Univ, Ctr Bioenvironm Res, Xavier Univ, Ctr Bioenvironm Res, Coypu Fdn, Greater New Orleans Fdn, Natl Inst Enviornm Hlth Sci, USN Off Res, USDA, W Alton Jones Fdn DE estrogen receptor; estrogen insensitivity; uterus; ovary ID TRANSCRIPTION FACTOR GATA-1; ALPHA-KNOCKOUT MOUSE; CAMPOMELIC DYSPLASIA; OVARIAN PHENOTYPE; SEX REVERSAL; RAT OVARY; EXPRESSION; BETA; GENE; CELLS AB The estrogen receptor (ER) exists in two known forms, ERalpha and ERbeta, and acts as a ligand-inducible transcription factor to fulfill critical roles in reproductive physiology. Although in vitro studies suggest the ERs may play redundant roles, a dissimilar tissue distribution indicates otherwise. Therefore, to gain insight into the role of each ER form, individual lines of mice lacking each respective receptor, as well as mice lacking both ER forms, were generated. alphaERKO and betaERKO female mice possess a normally developed reproductive tract and maintain expression of the opposite ER. The alphaERKO female Is infertile and exhibits a hypoplastic uterus that is refractory to estrogens. The ovaries of the alphaERKO female are consistently polycystic and lack indications of spontaneous ovulation. In contrast, the betaERKO female exhibits a hormonally responsive uterus and grossly normal ovaries, but is subfertile In terms of the frequency and size of litters. Immature females of both ERKO lines successfully ovulate viable ova when superovulated with exogenous gonadotropins, yet the average yield of ooctyes is reduced. Mice lacking both known ER forms (alphabetaERKO) are infertile, possess the expected reproductive tract structures, but exhibit a remarkably distinct ovarian phenotype characterized by postnatal loss of oocytes and redifferentiation of the remaining somatic cells to Sertoli-like cells. This "sex-reversal" in the alphabetaERKO ovary is accompanied by the ectopic expression of testis-specific genes, for example, Sox9 and sulfated-glycoprotein-2. C1 Natl Inst Environm Hlth Sci, Lab Reproduct & Dev Toxicol, Receptor Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. RP Korach, KS (reprint author), Natl Inst Environm Hlth Sci, Lab Reproduct & Dev Toxicol, Receptor Biol Sect, NIH, MD B3-02 POB 12233, Res Triangle Pk, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 26 TC 53 Z9 60 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-348-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 948 BP 1 EP 8 PG 8 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Reproductive Biology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Reproductive Biology GA BT69F UT WOS:000173775200001 PM 11795387 ER PT J AU Hsing, AW Chang, L Nomura, AM Isaacs, WB Armenian, HK AF Hsing, AW Chang, L Nomura, AM Isaacs, WB Armenian, HK TI A glimpse into the future SO EPIDEMIOLOGIC REVIEWS LA English DT Article C1 NCI, Div Can Epidemiol & Genet, Rockville, MD 20852 USA. Natl Yang Ming Univ, Shu Ten Urol Res Ctr, Taipei 112, Taiwan. Kuakini Med Ctr, Japan Hawaii Canc Ctr, Honolulu, HI 96817 USA. Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Hsing, AW (reprint author), NCI, Div Can Epidemiol & Genet, 6120 Execut Blvd,Room 7058,Execut Plaza S,MSC 723, Rockville, MD 20852 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X J9 EPIDEMIOL REV JI Epidemiol. Rev. PY 2001 VL 23 IS 1 BP 2 EP 2 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 476PU UT WOS:000171238600002 PM 11588849 ER PT J AU Hsing, AW Devesa, SS AF Hsing, AW Devesa, SS TI Trends and patterns of prostate cancer: What do they suggest? SO EPIDEMIOLOGIC REVIEWS LA English DT Article ID UNITED-STATES; STEROID 5-ALPHA-REDUCTASE; SURVEILLANCE SERIES; INTERPRETING TRENDS; AFRICAN-AMERICAN; RISK-FACTORS; SRD5A2 GENE; LOS-ANGELES; MORTALITY; WHITE C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, EPS MSC 7234,6120 Execut Blvd, Rockville, MD USA. NR 51 TC 165 Z9 168 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X J9 EPIDEMIOL REV JI Epidemiol. Rev. PY 2001 VL 23 IS 1 BP 3 EP 13 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 476PU UT WOS:000171238600003 PM 11588851 ER PT J AU Isaacs, W Kainu, T AF Isaacs, W Kainu, T TI Oncogenes and tumor suppressor genes in prostate cancer SO EPIDEMIOLOGIC REVIEWS LA English DT Article ID IN-SITU HYBRIDIZATION; COMPARATIVE GENOMIC HYBRIDIZATION; ANDROGEN-RECEPTOR GENE; ALLELIC LOSS; RADICAL PROSTATECTOMY; HOMOZYGOUS DELETION; P53 PROTEIN; HIGH-GRADE; E-CADHERIN; IMMUNOHISTOCHEMICAL DETECTION C1 Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21205 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Isaacs, W (reprint author), Johns Hopkins Univ, Sch Med, Dept Urol, 600 N Wolfe St, Baltimore, MD 21205 USA. NR 97 TC 15 Z9 15 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X J9 EPIDEMIOL REV JI Epidemiol. Rev. PY 2001 VL 23 IS 1 BP 36 EP 41 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 476PU UT WOS:000171238600008 PM 11588853 ER PT J AU Hsing, AW AF Hsing, AW TI Hormones and prostate cancer: What's next? SO EPIDEMIOLOGIC REVIEWS LA English DT Article ID ANDROGEN RECEPTOR EXPRESSION; BINDING GLOBULIN; GROWTH-FACTORS; 5-ALPHA-REDUCTASE ACTIVITY; ESTROGEN-RECEPTOR; STEROID-HORMONES; SERUM ANDROGENS; ENERGY-BALANCE; SEX-HORMONES; IGF-I C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, EPS-MSC 7234,6120 Execut Blvd, Rockville, MD 20852 USA. NR 93 TC 122 Z9 125 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X J9 EPIDEMIOL REV JI Epidemiol. Rev. PY 2001 VL 23 IS 1 BP 42 EP 58 PG 17 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 476PU UT WOS:000171238600009 PM 11588854 ER PT J AU Strickler, HD Goedert, JJ AF Strickler, HD Goedert, JJ TI Sexual behavior and evidence for an infectious cause of prostate cancer SO EPIDEMIOLOGIC REVIEWS LA English DT Article ID POLYMERASE CHAIN-REACTION; HUMAN-PAPILLOMAVIRUS TYPE-16; SIMPLEX VIRUS TYPE-2; RISK-FACTORS; UNITED-STATES; KAPOSIS-SARCOMA; HPV DNA; ESOPHAGEAL CANCER; MARITAL-STATUS; CARCINOMA C1 Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10461 USA. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. RP Strickler, HD (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Social Med, 1300 Morris Pk Ave,Belfer Bldg,Room 1308-B, Bronx, NY 10461 USA. NR 89 TC 52 Z9 55 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X J9 EPIDEMIOL REV JI Epidemiol. Rev. PY 2001 VL 23 IS 1 BP 144 EP 151 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 476PU UT WOS:000171238600023 PM 11588840 ER PT J AU Hayes, RB AF Hayes, RB TI Gene-environment interrelations in prostate cancer SO EPIDEMIOLOGIC REVIEWS LA English DT Article ID ANDROGEN RECEPTOR GENE; CHROMOSOME 1Q42.2-43; SUSCEPTIBILITY LOCUS; BLADDER-CANCER; POPULATION STRATIFICATION; CAG REPEAT; RISK; ASSOCIATION; LINKAGE; POLYMORPHISM C1 NCI, Div Canc Epidemiol & Genet, Occupat Studies Branch, Bethesda, MD 20892 USA. RP Hayes, RB (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat Studies Branch, EPS 8114, Bethesda, MD 20892 USA. NR 44 TC 21 Z9 21 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X J9 EPIDEMIOL REV JI Epidemiol. Rev. PY 2001 VL 23 IS 1 BP 163 EP 167 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 476PU UT WOS:000171238600026 PM 11588843 ER PT J AU Potosky, AL Feuer, EJ Levin, DL AF Potosky, AL Feuer, EJ Levin, DL TI Impact of screening on incidence and mortality of prostate cancer in the United States SO EPIDEMIOLOGIC REVIEWS LA English DT Article ID DETROIT METROPOLITAN-AREA; RADICAL PROSTATECTOMY; SURVEILLANCE SERIES; INTERPRETING TRENDS; DETECTION PROJECT; INCIDENCE RATES; SURVIVAL RATES; CARCINOMA; ANTIGEN; MEN C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Potosky, AL (reprint author), NCI, Div Canc Control & Populat Sci, EPN Room 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. NR 35 TC 71 Z9 71 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X J9 EPIDEMIOL REV JI Epidemiol. Rev. PY 2001 VL 23 IS 1 BP 181 EP 186 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 476PU UT WOS:000171238600029 PM 11588846 ER PT J AU Inskip, PD AF Inskip, PD TI Frequent radiation exposures and frequency dependent effects: The eyes have it SO EPIDEMIOLOGY LA English DT Editorial Material ID MALIGNANT-MELANOMA; UVEAL MELANOMA; ULTRAVIOLET-RADIATION; RADIOFREQUENCY RADIATION; OUTDOOR WORK; HOST FACTORS; CANCER; RISK; SUN; TELEPHONES C1 NCI, Radiat Epidemiol Branch, Rockville, MD 20852 USA. RP Inskip, PD (reprint author), NCI, Radiat Epidemiol Branch, Execut Plaza S,Room 7052,6120 Execut Blvd, Rockville, MD 20852 USA. NR 42 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2001 VL 12 IS 1 BP 1 EP 4 DI 10.1097/00001648-200101000-00001 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 385LR UT WOS:000166006400001 PM 11138802 ER PT J AU Gilliland, FD Berhane, K Rapaport, EB Thomas, DC Avol, E Gauderman, WJ London, SJ Margolis, HG McConnell, R Islam, KT Peters, JM AF Gilliland, FD Berhane, K Rapaport, EB Thomas, DC Avol, E Gauderman, WJ London, SJ Margolis, HG McConnell, R Islam, KT Peters, JM TI The effects of ambient air pollution on school absenteeism due to respiratory illnesses SO EPIDEMIOLOGY LA English DT Article DE air pollution; ozone; respiratory illnesses and children; school absenteeism ID SOUTHERN CALIFORNIA COMMUNITIES; PULMONARY-FUNCTION; DIFFERING LEVELS; MEXICO-CITY; CHILDREN; ASTHMA; PARTICULATE; EXPOSURES; MORBIDITY; SYMPTOMS AB We investigated the relations between ozone (O-3), nitrogen dioxide (NO2), and respirable particles less than 10 mum in diameter (PM10) and school absenteeism in a cohort of 4th-grade school children who resided in 12 southern California communities. An active surveillance system ascertained the numbers and types of absences during the first 6 months of 1996. Pollutants were measured hourly at central-site monitors in each of the 12 communities. To examine acute effects of air pollution on absence rates, we fitted a two-stage time series model to the absence count data that included distributed lag effects of exposure adjusted for long-term pollutant levels. Short-term change in O-3, but not NO2 or PM10, was associated with a substantial increase in school absences from both upper and lower respiratory illness. An increase of 20 ppb of O-3 was associated with an increase of 62.9% [95% confidence interval (95% CI) = 18.4-124.1%] for illness-related absence rates, 82.9% (95% CI = 3.9-222.0%) for respiratory illnesses, 45.1% (95% CI = 21.3-73.7%) for upper respiratory illnesses, and 173.9% (95% CI = 91.3-292.3%) for lower respiratory illnesses with wet cough. The short-term effects of a 20-ppb change of O-3 on illness-related absenteeism were larger in communities with lower long-term average PM10 [223.5% (95% CI = 90.4-449.7)] compared with communities with high average levels [38.1% (95% CI = 8.5-75.8)]. Increased school absenteeism from O-3 exposure in children is an important adverse effect of ambient air pollution worthy of public policy consideration. C1 Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Calif Air Resources Board, Sacramento, CA USA. RP Gilliland, FD (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, 1540 Alcazar St,CHP 236, Los Angeles, CA 90033 USA. OI London, Stephanie/0000-0003-4911-5290 FU NHLBI NIH HHS [1R01 HL61768]; NIEHS NIH HHS [5 P30 ES07048-02, 5ES09581-01] NR 45 TC 89 Z9 96 U1 3 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2001 VL 12 IS 1 BP 43 EP 54 DI 10.1097/00001648-200101000-00009 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 385LR UT WOS:000166006400009 PM 11138819 ER PT J AU Hirvonen, T Pietinen, P Virtanen, M Ovaskainen, ML Hakkinen, S Albanes, D Virtamo, J AF Hirvonen, T Pietinen, P Virtanen, M Ovaskainen, ML Hakkinen, S Albanes, D Virtamo, J TI Intake of flavonols and flavones and risk of coronary heart disease in male smokers SO EPIDEMIOLOGY LA English DT Article DE antioxidants; coronary heart disease; flavonoids; diet ID POTENTIALLY ANTICARCINOGENIC FLAVONOIDS; CARDIOVASCULAR-DISEASE; ANTIOXIDANT; QUERCETIN; VEGETABLES; MYRICETIN; VALIDITY; INHIBIT; FINLAND; FRUIT AB Flavonols and flavones are antioxidant polyphenolic compounds found in tea, vegetables, fruits, and wine. In experimental studies they have been effective free radical scavengers, metal chelators, and antithrombotic agents. In the few epidemiologic studies of these agents, some have suggested an inverse association between intake of flavonols and flavones and the risk of cardiovascular disease. Our study population comprised 25,372 male smokers, 50-69 years of age, with no previous myocardial infarction. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, which was a randomized, double-blind, placebo-controlled trial with daily supplementation of alpha-tocopherol (50 mg per day) and/or beta-carotene (20 mg per day). The men completed a validated dietary questionnaire at baseline. After 6.1 years of follow-up, there were 1,122 nonfatal myocardial infarctions and 815 coronary deaths. In the multivariate model, the relative risk of nonfatal myocardial infarction was 0.77 (95% confidence interval = 0.64-0.93) among men in the highest (median 18 mg per day) compared with the lowest (median 4 mg per day) quintile of flavonol and flavone intake. The respective relative risk for coronary death was 0.89 (95% confidence interval = 0.71-1.11). Thus, intake of flavonols and flavones was inversely associated with nonfatal myocardial infarction, whereas there was a weaker association with coronary death. C1 Natl Publ Hlth Inst, Dept Nutr, FIN-00300 Helsinki, Finland. Univ Kuopio, Dept Clin Nutr, FIN-70211 Kuopio, Finland. Univ Kuopio, Dept Physiol, FIN-70211 Kuopio, Finland. NCI, Div Clin Sci, Bethesda, MD 20892 USA. RP Hirvonen, T (reprint author), Natl Publ Hlth Inst, Dept Nutr, Mannerheimintie 166, FIN-00300 Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-CN-45165] NR 21 TC 108 Z9 113 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2001 VL 12 IS 1 BP 62 EP 67 DI 10.1097/00001648-200101000-00011 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 385LR UT WOS:000166006400011 PM 11138821 ER PT J AU Costantini, AS Miligi, L Kriebel, D Ramazzotti, V Rodella, S Scarpi, E Stagnaro, E Tumino, R Fontana, A Masala, G Vigano, C Vindigni, C Crosignani, P Benvenuti, A Vineis, P AF Costantini, AS Miligi, L Kriebel, D Ramazzotti, V Rodella, S Scarpi, E Stagnaro, E Tumino, R Fontana, A Masala, G Vigano, C Vindigni, C Crosignani, P Benvenuti, A Vineis, P TI A multicenter case-control study in Italy on hematolymphopoietic neoplasms and occupation SO EPIDEMIOLOGY LA English DT Article DE hematolymphopoietic neoplasms; occupation; case-control study; Italy; gender ID NON-HODGKINS-LYMPHOMA; CHRONIC LYMPHOCYTIC LEUKEMIAS; ANIMAL BREEDING WORKERS; POPULATION CASE-CONTROL; MULTIPLE-MYELOMA; RISK-FACTORS; CIGARETTE-SMOKING; CANCER MORTALITY; HEMATOPOIETIC CANCER; HISTOLOGICAL TYPE AB We conducted a population-based, case-control study on hematolymphopoietic malignancies in 12 areas in Italy to investigate associations between different hematolymphopoietic malignancies and exposure to solvents and pesticides. We collected all incident cases 20-74 years of age from 12 areas, with a combined population of approximately 7 million residents. The control group was formed by a random sample of the study population. Data presented in this paper refer to 2,737 interviewed cases of 3,357 eligible cases and to 1,779 of 2,391 eligible controls. We analyzed risks associated with occupation using job-title information to evaluate disease pattern according to job category. An earlier publication presented results for women; here, we report the findings for men and discuss the overall patterns in both genders. The most consistent overall finding was an approximate doubling in relative risk for all four types of malignancies among male managers and related occupations. Several additional occupations were associated with elevated risk of one or more malignancies among men. These included cooks, waiters, and bartenders, and building caretakers and cleaners, for non-Hodgkin's lymphoma; textile workers and machinery fitters for Hodgkin's lymphoma; metal processors, material handlers, rubber workers, and painters for leukemia; and hairdressers, metal processors, tailors, electrical workers, and plumbers fur multiple myeloma. The finding of increased risk of non-Hodgkin's lymphoma among both male and female cooks, waiters, and bartenders has not been previously reported; nor has the elevated risk of leukemia among material handlers. Among people engaged in agriculture, those employed as tractor drivers and as "orchard, vineyard, and related tree and shrub workers" appeared to be at increased risk for hematolymphopoietic malignancies. C1 Azienda Osped Careggi, Ctr Study & Prevent Canc, Epidemiol Unit, I-50135 Florence, Italy. Univ Massachusetts, Dept Work Environm, Lowell, MA USA. Natl Canc Inst, Ist Regina Elena, Rome, Italy. Azienda Osped, Verona, Italy. Ist Oncol Romagnolo, Forli, Italy. Natl Canc Inst, Genoa, Italy. Canc Registry, Ragusa, Italy. Local Hlth Unit, Novara, Italy. Natl Canc Inst, Epidemiol Unit, I-20133 Milan, Italy. Univ Siena, Inst Pathol, I-53100 Siena, Italy. Azienda Osped S Giovanni, Canc Epidemiol Unit, Turin, Italy. Univ Turin, I-10124 Turin, Italy. RP Costantini, AS (reprint author), Azienda Osped Careggi, Ctr Study & Prevent Canc, Epidemiol Unit, Via San Salvi 12, I-50135 Florence, Italy. OI Scarpi, Emanuela/0000-0001-7230-9267; Masala, Giovanna/0000-0002-5758-9069 FU NCI NIH HHS [CA51086] NR 70 TC 52 Z9 52 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2001 VL 12 IS 1 BP 78 EP 87 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 385LR UT WOS:000166006400014 PM 11138825 ER PT J AU Tornwall, ME Virtamo, J Haukka, JK Albanes, D Huttunen, JK AF Tornwall, ME Virtamo, J Haukka, JK Albanes, D Huttunen, JK TI Life-style factors and risk for abdominal aortic aneurysm in a cohort, of Finnish male smokers SO EPIDEMIOLOGY LA English DT Article DE abdominal aortic aneurysm; cohort study; smoking; blood pressure; serum cholesterol; HDL cholesterol; diet ID CORONARY HEART-DISEASE; WESTERN-AUSTRALIA; CHOLESTEROL; POPULATION; ATHEROSCLEROSIS; EPIDEMIOLOGY; DEATH; DIET; MEN AB Prospective studies evaluating risk factors for abdominal aortic aneurysm are few. We studied the association of life-style factors with risk for abdominal aortic aneurysm among 29,133 male smokers 50-69 years of age, participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. During a mean follow-up of 5.8 years, 181 were diagnosed with ruptured abdominal aortic aneurysm or nonruptured abdominal aortic aneurysm plus aneurysmectomy. Risk for abdominal aortic aneurysm was positively associated with age [relative risk (RR) = 4.56, 95% confidence interval (CI) = 2.42-8.61 for >65 vs less than or equal to 55 years], smoking years (RR = 2.25, 95% CI = 1.33-3.81 for >40 vs less than or equal to 32 years), systolic blood pressure (RR = 1.92, 95% CI = 1.13-3.25 for >160 vs less than or equal to 130 mmHg), diastolic blood pressure (RR = 1.80, 95% CI = 1.05-3.08 for >100 vs less than or equal to 85 mmHg), and serum total cholesterol (RR = 1.85, 95% CI = 1.09-3.12 for >6.5 vs less than or equal to5.0 mmol/liter). High-density lipoprotein cholesterol showed a strong inverse association with risk for aortic aneurysm (RR = 0.16, 95% CI = 0.08-0.32 for >1.5 vs less than or equal to0.9 mmol/liter). High energy intake was associated with lower risk for aortic aneurysm (RR = 0.59, 95% CI = 0.38-0.94 for the highest quartile vs the lowest), whereas no associations with nutrients were evident. We conclude that classical risk factors fur atherosclerotic diseases seem to be important in pathogenesis of large abdominal aortic aneurysms. C1 KTL Natl Publ Hlth Inst, Dept Nutr, ATBC Study, Helsinki 00300, Finland. NCI, Bethesda, MD 20892 USA. RP Tornwall, ME (reprint author), KTL Natl Publ Hlth Inst, Dept Nutr, ATBC Study, Mannerheiminie 166, Helsinki 00300, Finland. RI Albanes, Demetrius/B-9749-2015; Haukka, Jari/G-1484-2014 OI Haukka, Jari/0000-0003-1450-6208 FU NCI NIH HHS [N01-CN-45165] NR 36 TC 39 Z9 44 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2001 VL 12 IS 1 BP 94 EP 100 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 385LR UT WOS:000166006400016 PM 11138827 ER PT J AU Boffetta, P Silverman, DT AF Boffetta, P Silverman, DT TI A meta-analysis of bladder cancer and diesel exhaust exposure SO EPIDEMIOLOGY LA English DT Review DE bladder neoplasms; diesel exhaust; occupation; meta analysis ID OCCUPATIONAL RISK-FACTORS; LOWER URINARY-TRACT; RAILWAY WORKERS; LUNG-CANCER; MORTALITY; MALES; MEN; DRIVERS; COHORT AB The aim of this study is to review and summarize the available epidemiologic studies of bladder cancer and occupational exposure to diesel exhaust. We retrieved relevant studies and abstracted their characteristics and results. We assessed the heterogeneity of the results to decide whether to perform a fixed-effects model meta-analysis. We identified 35 relevant studies. No overall meta-analysis was performed because of heterogeneity in results. Results of railroad workers (N = 14) suggested an increased occurrence of bladder cancer, but we did not conduct a meta-analysis. The summary relative risk (RR) among truck drivers was 1.17 (95% confidence interval [CI] = 1.06-1.29, 15 studies) and that among bus drivers was 1.33 (95% CI = 1.22-1.45, 10 studies). Ten studies considered diesel exhaust exposure based on a job exposure matrix or a similar approach; the summary RR for these studies was 1.13 (95% CI = 1.00-1.27). A positive dose-response relation was suggested by 10 of the 12 studies that provided relevant information. The summary RR for high diesel exposure was 1.44 (95% CI = 1.18-1.76). There was some evidence of publication bias, however, with a lack of small studies with null or negative results. Our review suggests that exposure to diesel exhaust may increase the occurrence of bladder cancer, but the effects of misclassification, publication bias, and confounding cannot be fully taken into account. C1 Int Agcy Res Canc, Unit Environm Canc Epidemiol, F-69008 Lyon, France. NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Boffetta, P (reprint author), Int Agcy Res Canc, Unit Environm Canc Epidemiol, 150 Cours Albert Thomas, F-69008 Lyon, France. NR 40 TC 64 Z9 66 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2001 VL 12 IS 1 BP 125 EP 130 DI 10.1097/00001648-200101000-00021 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 385LR UT WOS:000166006400021 PM 11138807 ER PT J AU Freedman, LS Al-Kayed, S Qasem, MB Barchana, M Boyiadzis, M El-Najjar, K Ibrahim, AS Salhab, AR Young, JL Roffers, S Kahan, E Harford, J Silbermann, M AF Freedman, LS Al-Kayed, S Qasem, MB Barchana, M Boyiadzis, M El-Najjar, K Ibrahim, AS Salhab, AR Young, JL Roffers, S Kahan, E Harford, J Silbermann, M TI Cancer registration in the Middle East SO EPIDEMIOLOGY LA English DT Editorial Material C1 Bar Ilan Univ, Dept Math Stat & Comp Sci, IL-52900 Ramat Gan, Israel. MOH, Jordan Canc Registry, Amman, Jordan. MOH, Israel Canc Registry, Jerusalem, Israel. MOH, Natl Canc Registry, Nicosia, Cyprus. Minist Hlth, Gaza, Israel. Cairo Univ, NCI, Cairo, Egypt. Beit Jalla Hosp, Bethlehem, Israel. Emory Univ, Atlanta, GA 30322 USA. Tel Aviv Univ, IL-69978 Tel Aviv, Israel. NCI, NIH, Bethesda, MD 20892 USA. Middle E Canc Consortium Off, Haifa, Israel. RP Freedman, LS (reprint author), Bar Ilan Univ, Dept Math Stat & Comp Sci, IL-52900 Ramat Gan, Israel. NR 8 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2001 VL 12 IS 1 BP 131 EP 133 DI 10.1097/00001648-200101000-00022 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 385LR UT WOS:000166006400022 PM 11138809 ER PT J AU Kupferberg, H AF Kupferberg, H TI Animal models used in the screening of antiepileptic drugs SO EPILEPSIA LA English DT Article DE seizure models; antiepileptic drugs; antiepileptic; screens. ID RECURRING HIPPOCAMPAL SEIZURES; ANTICONVULSANT DRUGS; PHARMACOLOGICAL FACTORS; LABORATORY EVALUATION; MAXIMAL ELECTROSHOCK; SEASONAL INFLUENCES; LOW MAGNESIUM; EPILEPTIFORM ACTIVITY; PARTIAL EPILEPSY; GENETIC MODELS AB The identification of potential therapeutic agents for the treatment of epilepsy requires the use of seizure models. These models can be either in vivo or in vitro, mechanism specific, mechanism independent, or seizure specific. To be predictive of therapeutic activity in patients, the models should approximate the events that precipitate seizures in humans. Model validation is defined by determining the pharmacologic characteristics using known clinically effective drugs. Mechanism-independent models were used to identify the first antiepileptic drugs [AEDs; e.g., phenobarbital (PB) and phenytoin (PHT)]. Mechanism-specific models are based on the fundamental process by which seizure propagation and inhibition occurs. Seizure-type models identify a compound's potential based on its effects on electrographic and behavioral response. No single model can be used to identify potential compounds adequately for development. The full pharmacologic-anticonvulsant profile of a potentially useful new therapeutic agent is required to ensure successful development. C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Kupferberg, H (reprint author), NINDS, NIH, 6001 Execut Blvd,Room 21077,MSC 9523, Bethesda, MD 20892 USA. NR 53 TC 61 Z9 63 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2001 VL 42 SU 4 BP 7 EP 12 DI 10.1046/j.1528-1157.2001.0420s4007.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 470HW UT WOS:000170866400002 PM 11564118 ER PT J AU Theodore, WH Gaillard, WD De Carli, C Bhatia, S Hatta, J AF Theodore, WH Gaillard, WD De Carli, C Bhatia, S Hatta, J TI Hippocampal volume and glucose metabolism in temporal lobe epileptic foci SO EPILEPSIA LA English DT Article DE epilepsy; hippocampus; glucose metabolism; MRI; PET ID POSITRON EMISSION TOMOGRAPHY; REGIONAL HYPOMETABOLISM; FDG-PET; SEIZURES; ATROPHY; DENSITY AB Purpose: Reports conflict on the relation of glucose metabolism to hippocampal volume in temporal lobe foci. Previous studies usually have used side-side ratios rather than regional metabolic rates. Methods: We measured hippocampal volume and glucose metabolism in 37 patients with temporal epileptogenic zones identified by ictal video-EEG telemetry. Metabolic rates were normalized to global brain mean. Results: Both 18-fluoro-2-deoxyglucose-PET and volumetric MRI lateralized the epileptic focus determined by ictal video-EEG. There were significant correlations between left-right metabolic asymmetry and hippocampal formation volume left-right ratios. Comparisons between normalized metabolism and hippocampal formation volume, ignoring the side of the epileptic focus, showed significant relations between left hippocampal volume and left inferior lateral temporal metabolism, right hippocampus and right inferior mesial temporal, and left hippocampus and left inferior mesial temporal metabolism. In contrast, when normalized metabolism was compared with hippocampal volume in the epileptic focus, no relation was found. Conclusions. Our study suggests that the relation between hippocampal volume and glucose metabolism breaks down in epileptic foci and that hypometabolism is not dependent on neuronal loss. It is consistent with data suggesting that hypometabolism is an independent predictor of surgical outcome. C1 NINDS, Clin Epilepsy Sect, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. RP Theodore, WH (reprint author), NINDS, Clin Epilepsy Sect, Epilepsy Res Branch, NIH, Bldg 10,Room 5N-250,10 Ctr Dr,MSC 1408, Bethesda, MD 20892 USA. NR 15 TC 42 Z9 42 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JAN PY 2001 VL 42 IS 1 BP 130 EP 132 DI 10.1046/j.1528-1157.2001.080874.x PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 401ER UT WOS:000166914800018 PM 11207796 ER PT J AU Bialer, M Johannessen, SI Kupferberg, HJ Levy, RH Loiseau, P Perucca, E AF Bialer, M Johannessen, SI Kupferberg, HJ Levy, RH Loiseau, P Perucca, E TI Progress report on new antiepileptic drugs: a summary of the Fifth Eilat Conference (EILAT V) SO EPILEPSY RESEARCH LA English DT Review DE antiepileptic drugs; drug development; epilepsy; pharmacology; clinical trials; conference ID COMPLEX PARTIAL SEIZURES; VAGUS NERVE-STIMULATION; ADD-ON THERAPY; REFRACTORY PARTIAL EPILEPSY; NEWLY-DIAGNOSED EPILEPSY; LEVETIRACETAM UCB L059; DOUBLE-BLIND TRIAL; LEFT VAGAL NERVE; INFANTILE SPASMS; LAMOTRIGINE MONOTHERAPY AB The Fifth Eilat Conference on New Antiepileptic Drugs (AEDs) took place at the Dan Hotel, Eilat, Israel, 25-29 June 2000. Basic scientists, clinical pharmacologists and neurologists from 20 countries attended the conference, whose main themes included recognition of unexpected adverse effects, new indications of AEDs, and patient-tailored AED therapy. According to tradition, the central part of the conference was devoted to a review of AEDs in development, as well to updates on AEDs that have been marketed in recent years. This article summarizes the information presented on drugs in preclinical and clinical development, including AWD 131-138, DP-valproate, harkoseride, LY300164, NPS 1776, NW 1015. pregabalin, remacemide, retigabine, rufinamide and valrocemide. The potential value of an innovative strategy, porcine embryonic GABAergic cell transplants, is also discussed. Finally, updates on felbamate, fosphenytoin, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin, zonisamide, and the antiepileptic vagal stimulator device are presented. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Hebrew Univ Jerusalem, Sch Pharm, IL-91120 Jerusalem, Israel. Hebrew Univ Jerusalem, Fac Med, David R Bloom Ctr Pharm, IL-91120 Jerusalem, Israel. Natl Ctr Epilepsy, Sandvika, Norway. NINDS, Epilepsy Branch, Bethesda, MD USA. Univ Washington, Dept Pharmaceut & Neurol Surg, Seattle, WA USA. Bordeaux Univ, Hosp Pellegrin, Dept Neurol, Bordeaux, France. Univ Pavia, Dept Internal Med & Therapeut, Clin Pharmacol Unit, Pavia, Italy. RP Bialer, M (reprint author), Hebrew Univ Jerusalem, Sch Pharm, IL-91120 Jerusalem, Israel. NR 198 TC 126 Z9 128 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD JAN PY 2001 VL 43 IS 1 BP 11 EP 58 DI 10.1016/S0920-1211(00)00171-6 PG 48 WC Clinical Neurology SC Neurosciences & Neurology GA 388WC UT WOS:000166205200002 PM 11137386 ER PT J AU Kannel, WB AF Kannel, WB TI Quest for an optimal population cardiovascular risk factor burden SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID CORONARY HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; MORTALITY; SURVIVAL; TRENDS C1 Boston Univ, Sch Med, Framingham Heart Dis Epidemiol Study, NHLBI, Boston, MA 02118 USA. RP Kannel, WB (reprint author), Boston Univ, Sch Med, Framingham Heart Dis Epidemiol Study, NHLBI, Boston, MA 02118 USA. NR 16 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JAN PY 2001 VL 22 IS 2 BP 105 EP 107 DI 10.1053/euhj.2000.2279 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 392BB UT WOS:000166389800002 PM 11161910 ER PT J AU Morasso, G Costantini, M Viterbori, P Bonci, F Del Mastro, L Musso, M Garrone, O Venturini, M AF Morasso, G Costantini, M Viterbori, P Bonci, F Del Mastro, L Musso, M Garrone, O Venturini, M TI Predicting mood disorders in breast cancer patients SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE breast cancer; Hospital Anxiety and Depression Scale; Psychological Distress Inventory; prediction ID QUALITY-OF-LIFE; HOSPITAL ANXIETY; PSYCHOLOGICAL MORBIDITY; PSYCHIATRIC MORBIDITY; DEPRESSION SCALE; WOMEN; DIAGNOSIS; MASTECTOMY; ADJUSTMENT; SURVIVORS AB Prediction of delayed psychiatric disorders in breast cancer patients by using a screening procedure was investigated. Two questionnaires, the Psychological Distress Inventory and the Hospital Anxiety and Depression Scale, were administered before and during chemotherapy, and at the first follow-up visit. A psychiatric diagnosis was assigned to 50 of the 132 patients (38%) evaluated at follow-up. Including a set of clinical and demographic variables in a logistic regression, increasing age (P = 0.001) and psychiatric history (P < 0.001) were associated with psychiatric morbidity at follow-up. The accuracy of the two questionnaires in predicting delayed psychiatric disorders increased from the evaluation before chemotherapy to the evaluation during chemotherapy. The most accurate prediction was observed for the concurrent evaluation at follow-up. The accuracy of three predictive models developed for each evaluation point by including age, psychiatric history and psychological distress measured with each of the two questionnaires was not significantly better than that observed using only the questionnaires' scores as predictors. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Natl Canc Inst, Dept Psychol, I-16132 Genoa, Italy. Natl Canc Inst, Univ Clin Epidemiol & Trials, Genoa, Italy. Osped S Chiara, Dept Med Oncol, I-56127 Pisa, Italy. Natl Canc Inst, Dept Med Oncol 1, Genoa, Italy. RP Morasso, G (reprint author), Natl Canc Inst, Dept Psychol, L R Benzi 10, I-16132 Genoa, Italy. RI costantini, massimo/G-1443-2012; OI VITERBORI, PAOLA/0000-0002-0241-646X; costantini, massimo/0000-0002-5293-7079; Del Mastro, Lucia/0000-0002-9546-5841 NR 33 TC 48 Z9 49 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2001 VL 37 IS 2 BP 216 EP 223 DI 10.1016/S0959-8049(00)00390-7 PG 8 WC Oncology SC Oncology GA 404FB UT WOS:000167085800017 PM 11166149 ER PT J AU Panzer, A Joubert, AM Bianchi, PC Hamel, E Seegers, JC AF Panzer, A Joubert, AM Bianchi, PC Hamel, E Seegers, JC TI The effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE chelidonine; Ukrain; alkaloid; tubulin polymerisation; spindle checkpoint ID ACTIVATED PROTEIN-KINASE; CANCER CELLS; SPINDLE CHECKPOINT; MAMMALIAN-CELLS; APOPTOSIS; INHIBITION; MITOSIS; GROWTH; PHOSPHORYLATION; SEPARATION AB Chelidonine is a tertiary benzophenanthridine alkaloid known to cause mitotic arrest and to interact weakly with tubulin. Our interest in chelidonine began when we found it to be a major contaminant of Ukrain(TM), which is a compound reported to be selectively toxic to malignant tells. The effects of chelidonine in two normal (monkey kidney and Hs27), two transformed (Vero and Graham 293) and two malignant (WHCO5 and HeLa) cell lines, were examined. Chelidonine proved to be a weak inhibitor of cell growth, but no evidence for selective cytotoxicity was found in this study. It was confirmed that chelidonine inhibits tubulin polymerisation (IC50 = 24 muM), explaining its ability to disrupt microtubular structure in cells. A G2/M arrest results, which is characterised by abnormal metaphase morphology, increased levels of cyclin B1 and enhanced cdc2 kinase activity. Exposure of all cell lines examined to chelidonine leads to activation of the stress-activated protein kinase/jun kinase pathway (SAPK/JNK). C1 Univ Pretoria, Dept Physiol, ZA-0001 Pretoria, South Africa. Univ Witwatersrand, Dept Surg, Witwatersrand, South Africa. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Joubert, AM (reprint author), Univ Pretoria, Dept Physiol, POB 2034, ZA-0001 Pretoria, South Africa. RI Joubert, Anna/F-8706-2010; OI Swanepoel, Annie/0000-0002-7074-5978 NR 40 TC 33 Z9 36 U1 1 U2 4 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD JAN PY 2001 VL 80 IS 1 BP 111 EP 118 DI 10.1078/0171-9335-00135 PG 8 WC Cell Biology SC Cell Biology GA 399UU UT WOS:000166831600012 PM 11211931 ER PT J AU Huang, S Lichtenauer, UD Pack, S Wang, C Kim, AC Lutchman, M Koch, CA Torres-Cruz, J Huang, SC Benz, EJ Christiansen, H Dockhorn-Dworniczak, B Poremba, C Vortmeyer, AO Chishti, AH Zhuang, Z AF Huang, S Lichtenauer, UD Pack, S Wang, C Kim, AC Lutchman, M Koch, CA Torres-Cruz, J Huang, SC Benz, EJ Christiansen, H Dockhorn-Dworniczak, B Poremba, C Vortmeyer, AO Chishti, AH Zhuang, Z TI Reassignment of the EPB4 center dot 1 gene to 1p36 and assessment of its involvement in neuroblastomas SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE EPB4 center dot 1; in vitro transcription translation; mutation analysis; neuroblastoma; RT-PCR; SSCP ID PROTEIN 4.1; DISTAL 1P; MEMBRANE; LOCALIZATION; DOMAIN; REGION AB Objectives EPB4.1 has been previously mapped to human chromosome 1p33-p34.2. In contradiction to this chromosomal location, we have mapped EPB4.1-1p36 by using fluorescence in situ hybridization and radiation hybrid mapping. In neuroblastomas, deletions of the telomeric end of chromosome 1 (1p36) are the most common genetic aberration. Methods We investigated whether genetic aberrations of EPB4.1 can be detected in some neuroblastomas by analyzing 72 tumours for EPB4.1 mutation, expression, and alternative splicing pattern. Furthermore, EPB4.1 protein from a neuroblastoma cell line was studied for its subcellular localization. Results Sequence changes could be detected in 14 out of 72 neuroblastomas, including missense, silent, and intronic changes. Duplex RT-PCR analysis revealed a subset of 11 tumours expressing significantly low levels of EPB4.1. Significant EPB4.1 sequence changes that were detected included an exon 4 G/A missense mutation (amino acid: V/I) that was shown to be associated with absence of wild-type EPB4.1 expression (3 tumours), an exon 8 G/A missense mutation (V/M) (1 tumour), and an intronic sequence change that was shown to be associated with the presence of an aberrant transcript (1 tumour). Splicing pattern analysis revealed that all EPB4.1 transcripts from tumours exclude exon 3, a splicing pattern for generating the 135 kDa isoform. EPB4.1 cDNA cloned from a neuroblastoma cell line produced a 135-kDa protein with a cytoplasm/membrane localization. Conclusions Out of 72 neuroblastomas we have identified 11 tumours with impaired EPB4.1 expression and 5 tumours with significant sequence changes. We also found that the 135 kDa isoform is the main EPB4.1 product in neuroblastoma. EPB4.1 cDNA from a neuroblastoma cell line produced a 135-kDa protein and displayed a cytoplasm/membrane localization in transfected cells. C1 NINCDS, Mol Pathogenesis Unit, SNB, NIH, Bethesda, MD 20892 USA. NICHHD, PREB, NIH, Bethesda, MD USA. St Elizabeths Med Ctr, Sect Hematol Oncol Res, Boston, MA 02135 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Univ Marburg, Dept Pediat Hematol & Oncol, Marburg, Germany. Univ Munster, Gerhard Domagk Inst Pathol, D-48149 Munster, Germany. Tufts Univ, Sch Med, Dept Anat & Cellular Biol, Boston, MA 02111 USA. RP Zhuang, Z (reprint author), NINCDS, Mol Pathogenesis Unit, SNB, NIH, Bldg 10,Room 5D32,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Koch, Christian/A-4699-2008; Pack, Svetlana/C-2020-2014; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 NR 15 TC 17 Z9 18 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PY 2001 VL 31 IS 10 BP 907 EP 914 DI 10.1046/j.1365-2362.2001.00892.x PG 8 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 483VB UT WOS:000171655600012 PM 11737230 ER PT J AU Burgdorfer, W AF Burgdorfer, W TI Arthropod-borne spirochetoses: A historical perspective SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Editorial Material ID BORRELIA-BURGDORFERI; LYME-DISEASE; CULTIVATION C1 NIAID, Rocky Mt Lab, Hamilton, MT 59840 USA. RP Burgdorfer, W (reprint author), NIAID, Rocky Mt Lab, 903 S 4th St, Hamilton, MT 59840 USA. NR 23 TC 11 Z9 11 U1 1 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD JAN PY 2001 VL 20 IS 1 BP 1 EP 5 DI 10.1007/s10096-001-8034-7 PG 5 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 401EE UT WOS:000166913700001 PM 11245316 ER PT J AU Tassinari, T Parodi, S Badino, R Vercelli, M AF Tassinari, T Parodi, S Badino, R Vercelli, M TI Mortality trend for multiple sclerosis in Italy (1974-1993) SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE mortality trend; multiple sclerosis; geographic distribution ID WORLD AB The prevalence of multiple sclerosis (MS) in Italy is one of the highest in Europe, estimated proportions ranging between 32 and 69 cases per 100,000. An update of mortality time trend analyses can help trace a picture of the evolution of the disease and contribute to the interpretation of differences related to latitude and gender. Standardized mortality ratios (SMR) were computed for the 1974-1993 calendar period, using the pooled data set as standard. World population was the standard used to estimate age-adjusted rates for all Italy, while for selected regions the 1991 Italian population was utilized. Time trend analysis was performed using the Poisson regression model and the variation of mortality rates in time was expressed as mean difference per cent per year. Age-adjusted rates per million inhabitants were 4.1 for males and 5.0 for females. Northern Italian regions showed higher MS mortality rates than Central and Southern regions and Sicily, particularly in females; the effect was less evident in Sardinia. Time trend analysis by area showed a mortality decrease in Northern Italy (-1.15%) that reached statistical significance for men. In central regions a slight increase of borderline statistical significance (+1.03%) was observed only in women, while in the South and Sicily a statistically significant increase was seen in both males (+2.14%) and females (+3.09%). The analysis of the time trend for all Italy did not reveal significant variations in male mortality; by contrast, a slight, but statistically significant, increase (+0.88%) was observed in female mortality. Analysis of age-adjusted MS mortality rates in each region suggested the presence of an effect due to latitude. The occurrence of an increasing trend in Southern Italian regions and Sicily deserves further investigation. C1 Azienda Osped, Osped S Corona, Savona, Italy. RP Vercelli, M (reprint author), Natl Canc Inst, Ligurian Canc Registry, Largo R Benzi 10, I-16132 Genoa, Italy. OI Vercelli, Marina/0000-0002-9757-2616 NR 26 TC 10 Z9 11 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0393-2990 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PY 2001 VL 17 IS 2 BP 105 EP 110 DI 10.1023/A:1017939924157 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 471XG UT WOS:000170953500001 PM 11599682 ER PT J AU Aganna, E Aksentijevich, I Hitman, GA Kastner, DL Hoepelman, AIM Posma, FD Zweers, EJK McDermott, MF AF Aganna, E Aksentijevich, I Hitman, GA Kastner, DL Hoepelman, AIM Posma, FD Zweers, EJK McDermott, MF TI Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a Dutch family: evidence for a TNFRSF1A mutation with reduced penetrance SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE TNFRSF1A mutation; TRAPS; penetrance; plasma TNFRSF1A levels AB Mutations of the tumor necrosis factor receptor 1 (TNFRSF1A) gene underly susceptibility to a subset of autosomal dominant recurrent fevers (ADRFs). We report on a two-generation six-member Dutch family in which a novel R92P mutation and reduced plasma TNFRSF1A levels were found in all the children, including two who are unaffected. However, only the daughter proband and father exhibited a typical TNF-receptor associated periodic syndrome (TRAPS) phenotype. PCR-RFLP analysis revealed that the mutation was not present in 120 control chromosomes from unaffected Dutch individuals. As this R92P mutation is present in two unaffected carriers it appears to be less penetrant than previously reported TNFRSF1A mutations involving cysteine residues in the extracellular domains. C1 Univ London Queen Mary & Westfield Coll, St Bartholomews & Royal London Sch Med Dent, Dept Diabet & Metab Med, Mol Med Unit, London E1 4NS, England. NIAMSD, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. Univ Utrecht, Med Ctr, Dept Med, Div Infect Dis & AIDS, NL-3508 TC Utrecht, Netherlands. Univ Utrecht, Med Ctr, Eijkman Winkler Inst, NL-3508 TC Utrecht, Netherlands. Twenteborg Hosp, Dept Clin Chem, Almelo, Netherlands. RP McDermott, MF (reprint author), Royal London Hosp, 5th Floor,Alexandra Wing, London E1 1BB, England. NR 8 TC 28 Z9 29 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD JAN PY 2001 VL 9 IS 1 BP 63 EP 66 DI 10.1038/sj.ejhg.5200573 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 400MH UT WOS:000166875100012 PM 11175303 ER PT J AU Ida, H Rennert, OM Kobayashi, M Eto, Y AF Ida, H Rennert, OM Kobayashi, M Eto, Y TI Effects of enzyme replacement therapy in thirteen Japanese paediatric patients with Gaucher disease SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Article DE enzyme replacement therapy; growth indices; haematological and laboratory values; paediatric Gaucher disease ID MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; ALGLUCERASE; CHILDREN; MUTATIONS; GENETICS; REGIMEN AB To determine treatment effects in the unique and previously internationally unreported Japanese paediatric patient population with Gaucher disease (GD), we analysed six response parameters among 13 patients given enzyme replacement therapy (ERT). Also to obtain insights into optimising maintenance dosing, through subgroup analysis we retrospectively examined effects of three ERT dose reduction schedules from a starting regimen of 60 U/kg of body weight every 2 weeks. Our patients included 11 males and two females, 11 individuals with possible type 1 and two individuals with type 3b GD, six individuals with the L444P/F2131 genotype and five with the L444P/L444P genotype, and five who had been splenectomised. Despite different mutation prevalence, Japanese patients with GD, like their counterparts from other ethnic groups, generally benefitted from ERT. However, early and marked ERT dose reduction (from 60 U/kg to 30 or 15 U/kg every 2 weeks within less than or equal to6 months) was associated with insufficient improvement of mean haemoglobin level and relative height and with insufficient improvement or worsening of platelet count. Only the subgroup given 60 U/kg of ERT every 2 weeks for 36 months had significant improvement in mean haemoglobin, platelet count, angiotensin-converting enzyme and acid phosphatase levels and relative height at 36 months. Conclusion These data suggest that long-term high dose enzyme replacement therapy may be required to obtain sufficient improvement to maintain health among paediatric patients with severe Gaucher disease. C1 Jikei Univ, Sch Med, Dept Paediat, Minato Ku, Tokyo 105, Japan. Jikei Univ, Sch Med, Dept Gene Therapy, Inst DNA Med, Tokyo 105, Japan. NICHD, Ctr Res Mother & Children, NIH, Bethesda, MD USA. RP Ida, H (reprint author), Jikei Univ, Sch Med, Dept Paediat, Minato Ku, 3-25-8 Nishi Shinbashi, Tokyo 105, Japan. NR 17 TC 8 Z9 10 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6199 J9 EUR J PEDIATR JI Eur. J. Pediatr. PD JAN PY 2001 VL 160 IS 1 BP 21 EP 25 DI 10.1007/PL00008411 PG 5 WC Pediatrics SC Pediatrics GA 389EG UT WOS:000166225200003 PM 11195013 ER PT J AU Pras, E Aksentijevich, I Shinar, Y Kastner, DL Achiron, A AF Pras, E Aksentijevich, I Shinar, Y Kastner, DL Achiron, A TI Lack of evidence for an association between two genetic polymorphisms in the tumor necrosis factor receptor 1 gene and multiple sclerosis in Ashkenazi Jews SO EUROPEAN NEUROLOGY LA English DT Article DE multiple sclerosis; TNFR1; Ashkenazi association; polymorphism ID SUSCEPTIBILITY; ENCEPHALOMYELITIS; MICE AB Multiple sclerosis (MS) is a multifactorial disease with a documented genetic component. Recent experimental models suggested a role for the tumor necrosis factor receptor 1 (TNFR1) in the pathogenesis of the disease. We compared the frequency of two polymorphisms from TNFR1, located in exon 1 and intron 6, in 94 Jewish Ashkenazi MS patients and 83 healthy Ashkenazi controls. No significant differences were observed for both polymorphisms between the patients and the controls. These findings suggest that genetic variants in TNFR1 do not play a significant role in Ashkenazi Jews. Copyright (C) 2001 S. Karger AG, Basel. C1 Chaim Sheba Med Ctr, Danek Gertner Inst Human Genet, IL-52621 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Heller Inst Med Sci, Tel Hashomer, Israel. Chaim Sheba Med Ctr, Multiple Sclerosis Clin, Tel Hashomer, Israel. Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel. Natl Inst Hlth, Genet Sect, NIAMSD, Bethesda, MD USA. RP Pras, E (reprint author), Chaim Sheba Med Ctr, Danek Gertner Inst Human Genet, IL-52621 Tel Hashomer, Israel. EM epras@post.tau.ac.il NR 17 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0014-3022 J9 EUR NEUROL JI Eur. Neurol. PY 2001 VL 46 IS 3 BP 153 EP 155 DI 10.1159/000050789 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 484ZA UT WOS:000171722900008 PM 11598334 ER PT B AU Leshner, AI AF Leshner, AI GP NCASA TI Keynote address SO EXAMINING THE RELATIONSHIP BETWEEN SUBSTANCE ABUSE AND LEARNING DISABILITIES LA English DT Proceedings Paper CT Conference on Substance Abuse and Learning Disabilities CY FEB, 1999 CL Natl Ctr Addict & Substance Abuse, Columbia Univ, New York, NY SP Natl Ctr Learning Disabilities, NIDA, Carnegie Fdn, Ira Harris Fdn HO Natl Ctr Addict & Substance Abuse, Columbia Univ C1 Natl Inst Drug Abuse, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PRO-ED INC PI AUSTIN PA 8700 SHOAL CREEK RD, AUSTIN, TX 78758-9965 USA BN 0-89079-874-5 PY 2001 BP 8 EP 14 PG 7 WC Substance Abuse; Psychology, Developmental SC Substance Abuse; Psychology GA BBG38 UT WOS:000225432100002 ER PT B AU Weinberg, NZ AF Weinberg, NZ GP NCASA TI Risk factors for adolescent substance abuse SO EXAMINING THE RELATIONSHIP BETWEEN SUBSTANCE ABUSE AND LEARNING DISABILITIES LA English DT Proceedings Paper CT Conference on Substance Abuse and Learning Disabilities CY FEB, 1999 CL Natl Ctr Addict & Substance Abuse, Columbia Univ, New York, NY SP Natl Ctr Learning Disabilities, NIDA, Carnegie Fdn, Ira Harris Fdn HO Natl Ctr Addict & Substance Abuse, Columbia Univ ID POPULATION-BASED SAMPLE; USE DISORDERS; FOLLOW-UP; DRUG-ABUSE; DEVELOPMENTAL PSYCHOPATHOLOGY; AGGRESSIVE-BEHAVIOR; ALCOHOL DEPENDENCE; FEMALE TWINS; BOYS; VULNERABILITY C1 Natl Inst Drug Abuse, Bethesda, MD 20892 USA. NR 64 TC 0 Z9 0 U1 2 U2 3 PU PRO-ED INC PI AUSTIN PA 8700 SHOAL CREEK RD, AUSTIN, TX 78758-9965 USA BN 0-89079-874-5 PY 2001 BP 32 EP 40 PG 9 WC Substance Abuse; Psychology, Developmental SC Substance Abuse; Psychology GA BBG38 UT WOS:000225432100004 ER PT S AU Wenthold, RJ Rubio, ME Petralia, RS AF Wenthold, RJ Rubio, ME Petralia, RS BE Turski, L Schoepp, DD Cavalheiro, EA TI Distribution and targeting of glutamate receptors in neurons SO EXCITATORY AMINO ACIDS: TEN YEARS LATER SE BIOMEDICAL AND HEALTH RESEARCH LA English DT Proceedings Paper CT Meeting on Excitatory Amino Acids - 10 Years Later CY NOV 18-22, 1998 CL MANAUS, BRAZIL SP Brazilian Acad Sci, Astra Arcus AB, Boehringer Ingelheim, Eisai London Res Labs, Eli Lilly & Co, Inst Drug REs, Merz & Co, Pfizer Inc, Schering AG, Solvay Pharmaceut, Sundon Suntory Inst Bioorgan Res, Tocris Cookson ID CULTURED HIPPOCAMPAL-NEURONS; DOMAIN-CONTAINING PROTEIN; CEREBELLAR GRANULE CELLS; CLIMBING FIBER SYNAPSES; NMDA RECEPTOR; POSTSYNAPTIC DENSITY; AMPA RECEPTORS; SURFACE EXPRESSION; PURKINJE-CELLS; SUBUNIT AB Most neurons express multiple ionotropic and metabotropic glutamate receptors, but recent studies show that they are not uniformly distributed at excitatory synapses throughout the neuron. This suggests that glutamate receptors are selectively targeted to populations of synapses and that the number and composition of receptors may be regulated at the level of the individual synapse. We have used postembedding immunogold labeling to characterize the distribution of glutamate receptors in the central nervous system. We have selected neurons which receive multiple excitatory inputs to address the question of whether or not these inputs have the same composition of postsynaptic receptors. These neurons include the fusiform cells of the dorsal cochlear nucleus, the Purkinje cell of the cerebellum, and the pyramidal cell of the hippocampus, By quantifying immunogold labeling, we demonstrate that the receptor composition can vary dramatically between two populations of synapses, and that their distributions can be developmentally regulated. C1 NIH, Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, Bethesda, MD 20892 USA. RP Wenthold, RJ (reprint author), NIH, Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, Bldg 10, Bethesda, MD 20892 USA. NR 42 TC 0 Z9 0 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0929-6743 BN 1-58603-072-8 J9 BIOM HLTH R PY 2001 VL 45 BP 1 EP 9 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Pharmacology & Pharmacy GA BT13N UT WOS:000172044900001 ER PT J AU Berardi, A Parasuraman, R Haxby, JV AF Berardi, A Parasuraman, R Haxby, JV TI Overall vigilance and sustained attention decrements in healthy aging SO EXPERIMENTAL AGING RESEARCH LA English DT Article ID AGE; GLUCOSE AB Age differences in sustained attention were investigated using a high-event rate digit-discrimination task at 6 levels of stimulus degradation (lasting 8.1 min each). Twenty-one young, 21 middle-aged, and 20 old healthy subjects were studied. Overall sensitivity (d') was equivalent in all groups. Although all subjects showed a sensitivity decrement over blocks, there were no age-related differences in sustained attention capacity. All subjects had larger decrements in d' over blocks at higher degradation levels. However, the performance decrement at higher degradation levels was equivalent in all groups, indicating similar decrement rates in sensitivity with increasing demands on effortful processing. These results indicate that overall levels of vigilance and the ability to sustain attention over time are equivalent in all groups under conditions requiring both automatic (low-degradation) and effortful (high-degradation) stimulus processing. C1 NIA, Neurosci Lab, Bethesda, MD 20892 USA. Catholic Univ Amer, Cognit Sci Lab, Washington, DC 20064 USA. RP Berardi, A (reprint author), Univ Metz, Dept Psychol, Ile Saulcy, F-57045 Metz 01, France. NR 36 TC 26 Z9 27 U1 0 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-073X J9 EXP AGING RES JI Exp. Aging Res. PD JAN PY 2001 VL 27 IS 1 BP 19 EP 39 DI 10.1080/03610730126014 PG 21 WC Geriatrics & Gerontology; Psychology SC Geriatrics & Gerontology; Psychology GA 382UB UT WOS:000165841800002 PM 11205528 ER PT J AU Alesci, S Bornstein, SR AF Alesci, S Bornstein, SR TI Intraadrenal mechanisms of DHEA regulation: A hypothesis for adrenopause SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES LA English DT Article DE DHEA; adrenal androgens; adrenopause; aging; cellular cross-talk ID CORTICOTROPIN-RELEASING-HORMONE; FETAL ADRENAL-CELLS; HUMAN ADRENOCORTICAL-CELLS; ANDROGEN-STIMULATING HORMONE; FIBROBLAST GROWTH-FACTOR; AGE-ASSOCIATED DECLINE; IN-SITU HYBRIDIZATION; DEHYDROEPIANDROSTERONE-SULFATE; STEROIDOGENIC ENZYME; CHROMAFFIN CELLS AB Dehydroepiandrosterone (DHEA) and its sulfate metabolite DHEAS are the major androgens secreted by the human adrenal gland. The specific control of these hormones remains unclear. While ACTH is a potent stimulator of DHEA secretion, other factors both systemic and local have been involved in adrenal androgen control. Here we review the extra and intra-adrenal regulation of DHEA and propose a hypothetical model for adrenal senescence. C1 NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Alesci, S (reprint author), NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 99 TC 14 Z9 15 U1 0 U2 0 PU JOHANN AMBROSIUS BARTH VERLAG PI HEIDELBERG PA IM WEIHER 10, D-69121 HEIDELBERG, GERMANY SN 0947-7349 J9 EXP CLIN ENDOCR DIAB JI Exp. Clin. Endocrinol. Diabet. PY 2001 VL 109 IS 2 BP 75 EP 82 DI 10.1055/s-2001-14826 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 422NE UT WOS:000168124400003 PM 11341302 ER PT J AU Pigarev, IN Nothdurft, HC Kastner, S AF Pigarev, IN Nothdurft, HC Kastner, S TI Neurons with large bilateral receptive fields in monkey prelunate gyrus SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE visual cortex; extrastriate areas; symmetry; area V4 ID MACAQUE MONKEY; VISUAL-CORTEX; STRIATE CORTEX; RHESUS-MONKEY; AREA V4; CONNECTIONS; ORGANIZATION; COLOR; CELLS; REPRESENTATION AB In single-cell recordings from the dorsocaudal part of the prelunate gyrus of an alert monkey (Macaca fascicularis) we found neurons with unexpectedly large receptive fields (RFs) that spread bilaterally into the contra- and ipsilateral visual fields. These neurons (n=82) appeared to be clustered in the periphery of V4. They were surrounded by neurons with relatively small (3-10 degrees) and unilateral RFs in the contralateral field with properties similar to those previously described for neurons in area V4. Bilateral RFs extended over large parts of the lower visual field but always spared the fovea. Receptive fields typically revealed two foci of maximal responsiveness that were arranged symmetrically in the ipsi- and contralateral fields. Twenty-six cells did not respond to stimuli along the vertical meridian; these neurons had two distinct RFs. The preference for stimulus orientation, color, or motion was similar in all parts of these large RFs. C1 Max Planck Inst Biophys Chem, AG Neurobiol 110, D-37070 Gottingen, Germany. Russian Acad Sci, Inst Problems Informat Transmiss, Moscow 101447, Russia. NIMH, Lab Brain & Cognit, LPP, Bethesda, MD 20892 USA. RP Nothdurft, HC (reprint author), Max Planck Inst Biophys Chem, AG Neurobiol 110, D-37070 Gottingen, Germany. NR 31 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JAN PY 2001 VL 136 IS 1 BP 108 EP 113 DI 10.1007/s002210000566 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 389EJ UT WOS:000166225400011 PM 11204404 ER PT J AU Hollyfield, JG Rayborn, ME Nishiyama, K Shadrach, KG Miyagi, M Crabb, JW Rodriguez, IR AF Hollyfield, JG Rayborn, ME Nishiyama, K Shadrach, KG Miyagi, M Crabb, JW Rodriguez, IR TI Interphotoreceptor matrix in the fovea and peripheral retina of the primate Macaca mulatta: Distribution and glycoforms of SPACR and SPACRCAN SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE SPACR; SPACRCAN; fovea; retina; interphotoreceptor matrix; monkey ID CHONDROITIN-SULFATE PROTEOGLYCAN; BINDING PROTEIN IRBP; CONE PHOTORECEPTORS; GLYCOSAMINOGLYCAN; GLYCOPROTEIN; LOCALIZATION; HYALURONAN; LINKAGE; REGION; SHEATH AB SPACR and SPACRCAN localization in the interphotoreceptor matrix (IPM) of the fovea and peripheral retina of Macaca mulatta was established with antibodies to these core proteins and the chondroitin sulfate epitopes and lectin binding properties of these molecules were defined. The IPM of both rods and cones labeled with anti-SPACR, anti-SPACRCAN, anti-Delta Di6S antibodies and wheat germ agglutinin (WGA). Whereas anti-SPACR and anti-SPACRCAN antibodies labeled rod and cone matrix compartments with similar intensity, the Delta Di6S chondroitin antibody labeling was more intense around cones than rods. Peanut lectin (PNA) labeling was present only around cones. No IPM labeling was observed with Delta Di0S-chondroitin or Delta Di4S-chondroitin antibodies. Western blots of undigested IPM extracts showed anti-SPACR immunoreactivity at 150 kDa, colocalizing with the position of WGA and PNA binding. In Western blots of the chondroitinase ABC digested sample and samples double digested with chondroitinase ABC and AC II. anti-SPACR immunoreactivity, WGA and PNA labeling intensity were virtually identical to that in the undigested sample, with prominent staining of the 150 kDa SPACR band. In contrast, anti-SPACRCAN immunoreactivity was not present in the undigested sample, but was evident in both the chondroitinase ABC and double digested samples as a broad band at approximately 230 kDa. Delta Di6S, Delta Di4S, WGA and PNA labeling colocalized with the anti-SPACRCAN immunoreactivity in the chondroitinase ABC digested sample. These findings indicate that SPACR and SPACRCAN are present around cones in the fovea and both rods and cones in the peripheral retina, but that the specific glycoforms of these molecules are different depending on whether present in the cone or rod associated IPM. (C) 2000 Academic Press. C1 Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Hollyfield, JG (reprint author), Cleveland Clin Fdn, Cole Eye Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. FU NEI NIH HHS [EY 02362] NR 31 TC 8 Z9 8 U1 1 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JAN PY 2001 VL 72 IS 1 BP 49 EP 61 DI 10.1006/exer.2000.0922 PG 13 WC Ophthalmology SC Ophthalmology GA 392BD UT WOS:000166390000006 PM 11133182 ER PT J AU Filenius, S Hormia, M Rissanen, J Burgeson, RE Yamada, Y Araki-Sasaki, K Nakamura, M Virtanen, I Tervo, T AF Filenius, S Hormia, M Rissanen, J Burgeson, RE Yamada, Y Araki-Sasaki, K Nakamura, M Virtanen, I Tervo, T TI Laminin synthesis and the adhesion characteristics of immortalized human corneal epithelial cells to laminin isoforms SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE basement membrane; cell adhesion; cornea; immunofluorescence; integrin; keratinocyte; laminin ID BASEMENT-MEMBRANE COMPONENTS; EXTRACELLULAR-MATRIX; MONOCLONAL-ANTIBODIES; FIBRONECTIN RECEPTOR; INTEGRIN RECEPTORS; CARCINOMA-CELLS; IV COLLAGEN; EXPRESSION; HEMIDESMOSOMES; COMPLEX AB We have studied the synthesis of laminins (Ln) and determined the specific integrins mediating the adhesion of immortalized human corneal epithelial cells to mouse Ln-1, and human Lns-5 and -10. Immunofluorescence microscopy of the cells demonstrated integrin alpha (2), alpha (3), alpha (6), beta (1) and beta (4) subunits, integrins alpha (6) and beta (4) being found in a typical 'leopard-skin' like manner. Immunoprecipitation studies showed that the cells produced alpha3, beta3 and gamma2 chains of Ln-5, but not Lns-1 or -10. In culture Ln-5 was found as small plaques beneath the adhering cells within 1 hr, while in 4 hr widely spread Ln-5 plaques were observed in colocalization with beta (4) integrin subunit. By using a quantitative cell adhesion assay and function-blocking monoclonal antibodies we showed that integrin beta (1) subunit plays a role in mediating corneal epithelial cell adhesion to mouse Ln-1. However, none of the available function-blocking antibodies to integrin alpha -subunits inhibited the adhesion. Integrin alpha (3)beta (1) complex mediated the adhesion of corneal epithelial cells to human Lns-5 and -10. Integrin complex alpha (3)beta (1), as well as laminin alpha (3) chain, was also shown to mediate cell adhesion to newly produced endogenous Ln-5. The present results show that integrin alpha (3)beta (1) complex mediates the adhesion of corneal epithelial cells to Lns-5 and -10, while a yet unknown integrin a subunit appears to play a role in the adhesion to Ln-1. The results also show that among corneal basement membrane laminins, Ln-5 is synthetized by epithelial cells while Ln-10 may be a product of keratocytes. (C) 2000 Academic Press. C1 Univ Helsinki, Inst Biomed, Dept Anat, FIN-00014 Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Ophthalmol, Helsinki, Finland. Harvard Univ, Massachusetts Gen Hosp E, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA USA. NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Osaka Univ, Sch Med, Dept Ophthalmol, Osaka, Japan. Santen Pharmaceut Co Ltd, Nara Res & Dev Ctr, Ophthalmol Res Div, Ikona Chi, Japan. RP Filenius, S (reprint author), Univ Helsinki, Inst Biomed, Dept Anat, FIN-00014 Helsinki, Finland. NR 71 TC 21 Z9 23 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JAN PY 2001 VL 72 IS 1 BP 93 EP 103 DI 10.1006/exer.2000.0933 PG 11 WC Ophthalmology SC Ophthalmology GA 392BD UT WOS:000166390000011 PM 11133187 ER PT J AU Bartke, A Brown-Borg, H Mattison, J Kinney, B Hauck, S Wright, C AF Bartke, A Brown-Borg, H Mattison, J Kinney, B Hauck, S Wright, C TI Prolonged longevity of hypopituitary dwarf mice SO EXPERIMENTAL GERONTOLOGY LA English DT Review ID GROWTH-HORMONE; TESTICULAR FUNCTION; PITUITARY; PIT-1 AB In two types of mutant dwarf mice, congenital deficiencies in pituitary function are associated with remarkably increased life expectancy. In this review, we will describe the key phenotypic characteristics of these animals, the evidence that they exhibit delayed aging, and the mechanisms that are suspected to account for their prolonged longevity. (C) 2001 Elsevier Science Inc. All rights reserved. C1 So Illinois Univ, Sch Med, Dept Physiol, Carbondale, IL 62901 USA. Univ N Dakota, Sch Med, Dept Physiol, Edwin James Res Ctr, Grand Forks, ND 58202 USA. NIA, NIH, Anim Ctr, Poolesville, MD 20837 USA. RP Bartke, A (reprint author), So Illinois Univ, Sch Med, Dept Physiol, Carbondale, IL 62901 USA. EM abartke@som.siu.edu RI Bartke, Andzej/D-6640-2017 OI Bartke, Andzej/0000-0002-2569-557X NR 30 TC 81 Z9 82 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 EI 1873-6815 J9 EXP GERONTOL JI Exp. Gerontol. PD JAN PY 2001 VL 36 IS 1 BP 21 EP 28 DI 10.1016/S0531-5565(00)00205-9 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 392VB UT WOS:000166432300003 PM 11162909 ER PT J AU Jacobson, KA Moro, S Hoffmann, C Kim, YC Kim, HS Ravi, RG Harden, TK Boyer, JL AF Jacobson, KA Moro, S Hoffmann, C Kim, YC Kim, HS Ravi, RG Harden, TK Boyer, JL TI Structurally related nucleotides as selective agonists and antagonists at P2Y(1) receptors SO FARMACO LA English DT Article; Proceedings Paper CT 16th International Symposium on Medicinal Chemistry CY SEP 18-22, 2000 CL BOLOGNA, ITALY DE G protein-coupled receptors; nucleotides; P2Y(1); molecular modeling ID PROTEIN-COUPLED RECEPTORS; EXTRACELLULAR LOOPS; DERIVATIVES; ANALOGS; POTENT; RECOGNITION; LIGANDS; PURINE; P1 AB The P2Y(1) receptor responds to adenine nucleotides and is present in platelets, heart, smooth muscles prostate, ovary, and brain. A selective antagonist may be useful as an antithrombotic agent. We have analyzed the binding site of this G protein-coupled receptor using ligand design, site-directed mutagenesis, and homology modeling based on rhodopsin. We have designed and synthesized a series of deoxyadenosine 3',5'-bisphosphate derivatives that act as antagonists, or, in some cases with small structural changes, as agonists or partial agonists. The 2-position accommodates Cl or thioethers, whereas the N-6-position is limited to Me or Et. T-Substitution with OH or OMe increases agonist efficacy over 2'-H. Using molecular modeling of the binding site, the oxygen atoms of the ribose moiety were predicted to be non-essential, i.e. no specific H-bonds with the receptor protein appear in the model. We have, therefore, substituted this moiety with carbocylics, smaller and larger rings, conformationally constrained rings, and acyclics, with retention of affinity for the receptor. With simplified pharmacophores we are exploring the steric and electronic requirements of the receptor binding site, and the structural basis of receptor activation. (C) 2001 Elsevier Science S.A. All rights reserved. C1 NIDDKD, Mol Recognit Sect, LBC, NIH, Bethesda, MD 20892 USA. Univ Padua, Dept Pharmaceut Sci, Mol Modeling Sect, Padua, Italy. Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC USA. RP Jacobson, KA (reprint author), NIDDKD, Mol Recognit Sect, LBC, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009 OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031116-20, Z99 DK999999] NR 18 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0014-827X J9 FARMACO JI Farmaco PD JAN-FEB PY 2001 VL 56 IS 1-2 BP 71 EP 75 AR PII S0014-827X(01)01023-0 DI 10.1016/S0014-827X(01)01023-0 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 586HW UT WOS:000177579400013 PM 11347970 ER PT J AU Tomatis, L Melnick, RL Haseman, J Barrett, JC Huff, J AF Tomatis, L Melnick, RL Haseman, J Barrett, JC Huff, J TI Alleged 'misconceptions' distort perceptions of environmental cancer risks SO FASEB JOURNAL LA English DT Article DE environmental carcinogens; assessment of risks; cancer prevention; carcinogenesis bioassay ID CARCINOGENIC POTENCY DATABASE; RODENT CARCINOGENS; AVOIDABLE RISKS; LUNG-CANCER; PERSPECTIVE; PREVENTION; CHEMICALS; HAZARDS; PESTICIDES; POLLUTION AB In a series of papers, Ames and col leagues allege that the scientific and public health communities have perpetuated a series of 'misconceptions' that resulted in inaccurate identification of chemicals that pose potential human cancer risks, and misguided cancer prevention strategies and regulatory policies. They conclude that exposures to industrial and synthetic chemicals represent negligible cancer risks and that animal studies have little or no scientific value for assessing human risks, Their conclusions are based on flawed and untested assumptions. For instance, they claim that synthetic residues on food can be ignored because 99.99% of pesticides humans eat are natural, chemicals in plants are pesticides, and their potential to cause cancer equals that of synthetic pesticides. Similarly, Ames does not offer any convincing scientific evidence to justify discrediting bioassays for identifying human carcinogens. Ironically, their arguments center on a ranking procedure that relies on the same experimental data and extrapolation methods they criticize as being unreliable for evaluating cancer risks. We address their inconsistencies and flaws, and present scientific facts and our perspectives surrounding Ames' nine alleged misconceptions. Our conclusions agree with the International Agency for Research on Cancer, the National Toxicology Program, and other respected scientific organizations: in the absence of human data, animal studies are the most definitive for assessing human cancer risks, Animal data should not be ignored, and precautions should be taken to lessen human exposures, Dismissing animal carcinogenicity findings would lead to human cancer cases as the only means of demonstrating carcinogenicity of environmental agents. This is unacceptable public health policy. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Huff, J (reprint author), NIEHS, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 53 TC 33 Z9 33 U1 1 U2 10 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN PY 2001 VL 15 IS 1 BP 195 EP 203 DI 10.1096/fj.99-1056com PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 390TH UT WOS:000166312400028 PM 11149907 ER PT J AU Andley, UP Song, Z Wawrousek, EF Brady, JP Bassnett, S Fleming, TP AF Andley, UP Song, Z Wawrousek, EF Brady, JP Bassnett, S Fleming, TP TI Lens epithelial cells derived from alpha B-crystallin knockout mice demonstrate hyperproliferation and genomic instability SO FASEB JOURNAL LA English DT Article DE molecular chaperone; nuclear; immortalization; ploidy ID NIH 3T3 FIBROBLASTS; LARGE-T-ANTIGEN; A-CRYSTALLIN; MOLECULAR CHAPERONE; SPINDLE CHECKPOINT; CYCLE REGULATION; MOUSE LENS; HA-RAS; V-MOS; EXPRESSION AB alphaB-crystallin is a member of the small heat shock protein family and can act as a molecular chaperone preventing the in vitro aggregation of other proteins denatured by heat or other stress conditions. Expression of alphaB-crystallin increases in cells exposed to stress and enhanced in tumors of neuroectodermal origin and in many neurodegenerative diseases. In the present study, we examined the properties of lens epithelial cells derived from mice in which the alphaB-crystallin gene had been knocked out. Primary rodent cells immortalize spontaneously in tissue culture with a frequency of 10(-5) to 10(-6). Primary lens epithelial cells derived from alphaB-crystallin(-/-) mice produced hyperproliferative clones at a frequency of 7.6 x 10(-2), four orders of magnitude greater than predicted by spontaneous immortalization (1), Hyperproliferative alphaB-crystallin(-/-) cells were shown to be truly immortal since they have been passaged for more than 100 population doublings without any diminution in growth potential. In striking contrast to the wild-type cells, which were diploid, the alphaB-crystallin(-/-) cultures had a high proportion of tetraploid and higher ploidy cells, indicating that the loss of alphaB-crystallin is associated with an increase in genomic instability. Further evidence of genomic instability of alphaB-crystallin(-/-) cells was observed when primary cultures were infected with Ad12SV40 hybrid virus. In striking contrast to wild-type cells, alphaB-crystallin(-/-) cells expressing SV40 T antigen exhibited a widespread cytocidal response 2 to 3 days after attaining confluence, indicating that SV40 T antigen enhanced the intrinsic genomic instability of alphaB-crystallin(-/-) lens epithelial cells. These observations suggest that the widely distributed molecular chaperone alphaB-crystallin may play an important nuclear role in maintaining genomic integrity. C1 Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Andley, UP (reprint author), Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, 660 S Euclid Ave,Campus Box 8096, St Louis, MO 63110 USA. RI Wawrousek, Eric/A-4547-2008 FU NEI NIH HHS [R01EY05681, EY02687, R01EY09852] NR 52 TC 58 Z9 60 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN PY 2001 VL 15 IS 1 BP 221 EP 229 DI 10.1096/fj.00-0296com PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 390TH UT WOS:000166312400031 PM 11149910 ER PT S AU Lands, WEM AF Lands, WEM BE Hamazaki, T Okuyama, H TI Impact of daily food choices on health promotion and disease prevention SO FATTY ACIDS AND LIPIDS-NEW FINDINGS SE WORLD REVIEW OF NUTRITION AND DIETETICS LA English DT Proceedings Paper CT 4th Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids (ISSFAL) CY JUN 04-09, 2000 CL TSUKUBA, JAPAN SP Int Soc Study Fatty Acids & Lipids, DHA & EPA Assoc, F Hoffmann, La Roche AG, Japan Federat Econ Org, Japan Soc Lipid Nutrit, Kentech Co, LTD, Osaka Pharmaceut Manufacturers Assoc, Pharmaceut Manufacturers Assoc Tokyo, Sankyo Fdn Life Sci, Uehara Mem Fdn ID POLYUNSATURATED FATTY-ACIDS; FISH; PLATELET; PHOSPHOLIPIDS; MEN C1 NIAAA, NIH, Bethesda, MD 20892 USA. RP Lands, WEM (reprint author), NIAAA, NIH, 6000 Execut Blvd,Suite 400,MSC 7003, Bethesda, MD 20892 USA. NR 14 TC 7 Z9 8 U1 0 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0084-2230 BN 3-8055-7182-8 J9 WORLD REV NUTR DIET JI World Rev.Nutr.Diet. PY 2001 VL 88 BP 1 EP 5 PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA BS86L UT WOS:000171272900001 PM 11935941 ER PT S AU Hibbeln, JR AF Hibbeln, JR BE Hamazaki, T Okuyama, H TI Seafood consumption and homicide mortality - A cross-national ecological analysis SO FATTY ACIDS AND LIPIDS-NEW FINDINGS SE WORLD REVIEW OF NUTRITION AND DIETETICS LA English DT Proceedings Paper CT 4th Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids (ISSFAL) CY JUN 04-09, 2000 CL TSUKUBA, JAPAN SP Int Soc Study Fatty Acids & Lipids, DHA & EPA Assoc, F Hoffmann, La Roche AG, Japan Federat Econ Org, Japan Soc Lipid Nutrit, Kentech Co, LTD, Osaka Pharmaceut Manufacturers Assoc, Pharmaceut Manufacturers Assoc Tokyo, Sankyo Fdn Life Sci, Uehara Mem Fdn ID ESSENTIAL FATTY-ACIDS; CEREBROSPINAL-FLUID; DEPRESSION; CHOLESTEROL; ALCOHOLICS; SEROTONIN; VIOLENT C1 NIAAA, Lab Membrane Biophys & Biochem, NIH, Bethesda, MD 20892 USA. RP Hibbeln, JR (reprint author), NIAAA, Lab Membrane Biophys & Biochem, NIH, Pk 5,Room 158,MCS 8115,12420 Parklawn Dr, Bethesda, MD 20892 USA. NR 13 TC 36 Z9 38 U1 0 U2 4 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0084-2230 BN 3-8055-7182-8 J9 WORLD REV NUTR DIET JI World Rev.Nutr.Diet. PY 2001 VL 88 BP 41 EP 46 PG 6 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA BS86L UT WOS:000171272900006 PM 11935968 ER PT J AU Rhee, S Agrawal, D Shrout, T Thumm, M AF Rhee, S Agrawal, D Shrout, T Thumm, M TI Investigation of high frequency (2.45 GHz, 30 GHz) sintering for Pb-based ferroelectrics and microscale functional devices SO FERROELECTRICS LA English DT Article; Proceedings Paper CT 3rd Asian Meeting on Ferroelectricity (AMF-3) CY DEC 12-15, 2000 CL HONG KONG, PEOPLES R CHINA DE microwave sintering; PZT; actuators; transducers AB Microwave sintering of PZT-based ceramics was investigated using multimode heating at 2.45 and 30 GHz and compared to conventional thermal processing. For PZT-5 and PZT-5H ceramics, microwave processing resulted in a reduction of sintering temperature by more than 150degreesC. Of significance to the production of high surface area lead-based components, minimal PbO volatility was detected for samples processed as high as 1200degreesC. In contrast to conventionally processed PZTs, no grain size dependency of the dielectric and piezoelectric properties was observed. Microscale functional components processed using microwave sintering included 1-3 piezoelectric composites, PZT fibers, and multilayer actuators. C1 Penn State Univ, NIH, Transducer Resource Ctr, University Pk, PA 16802 USA. Penn State Univ, Mat Res Lab, University Pk, PA 16802 USA. Forschungszentrum Karlsruhe, Inst Pulsed Power & Microwave Technol, D-76021 Karlsruhe, Germany. Univ Karlsruhe, Inst Microwaves & Elect, Karlsruhe, Germany. RP Rhee, S (reprint author), Penn State Univ, NIH, Transducer Resource Ctr, University Pk, PA 16802 USA. NR 6 TC 4 Z9 4 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0015-0193 J9 FERROELECTRICS JI Ferroelectrics PY 2001 VL 261 IS 1-4 BP 679 EP 684 PG 6 WC Materials Science, Multidisciplinary; Physics, Condensed Matter SC Materials Science; Physics GA 580BX UT WOS:000177215400002 ER PT B AU Lipman, DJ AF Lipman, DJ BE Layne, SP Beugelsdijk, TJ Patel, CKN TI Input/Output of high-throughput biology: Experience of the National Center for Biotechnology Information SO FIREPOWER IN THE LAB: AUTOMATION IN THE FIGHT AGAINST INFECTIOUS DISEASES AND BIOTERRORISM LA English DT Proceedings Paper CT Colloquium on Automation in Threat Reduction and Infectious Disease Research CY APR 29-30, 1999 CL NATL ACAD SCI, WASHINGTON, D.C. SP Ctr Dis Control & Prevent, US DOE, US Dept HHS, Off Emergency Preparedness, Los Alamos Natl Lab, Natl Acad Engn, Univ Calif Los Angeles, Assoc Lab Automat HO NATL ACAD SCI ID HUMAN GENES; MAP C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Lipman, DJ (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU JOSEPH HENRY PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA BN 0-309-06849-5 PY 2001 BP 85 EP 91 PG 7 WC Automation & Control Systems; Biotechnology & Applied Microbiology; Food Science & Technology; Infectious Diseases; Medicine, Research & Experimental SC Automation & Control Systems; Biotechnology & Applied Microbiology; Food Science & Technology; Infectious Diseases; Research & Experimental Medicine GA BU88C UT WOS:000177289400007 ER PT J AU Liberski, PP Bratosiewicz, J Walis, A Kordek, R Jeffrey, M Brown, P AF Liberski, PP Bratosiewicz, J Walis, A Kordek, R Jeffrey, M Brown, P TI A special report I. Prion protein (PrP) - amyloid plaques in the transmissible spongiform encephalopathies, or prion diseases revisited SO FOLIA NEUROPATHOLOGICA LA English DT Review DE PrP-amyloid plaques; electron microscopy; immunohistochemistry; CJD; GSS; kuru ID STRAUSSLER-SCHEINKER-DISEASE; CREUTZFELDT-JAKOB-DISEASE; 87V MURINE SCRAPIE; TRANSGENIC MICE; PRNP GENE; TUBULOVESICULAR STRUCTURES; ELECTRON-MICROSCOPY; NO ALTERATIONS; LOCALIZATION; ANTIBODIES AB We present a retrospective analysis of PrP-amyloid plaques encountered in CJD and GSS. In human TSEs (kuru, CJD and GSS) several PrP-immunopositive plaques and plaque-like deposits were detected. In kuru, plaques were typical "kuru" plaques - stellate structures deposited mostly in the granular- and Purkinje-cell layer of the cerebellum. Many smaller or larger clusters were visible but, in contrast to GSS, they never merged together to form multicentric plaques. In all cases of GSS, plaques were localised in the granular- and Purkinje-celI layer and the molecular cell layer. There were many different forms of plaques: from kuru plaques (unicentric stellate plaques) to clusters of unicentric plaques, which by merging eventually formed "multicentric plaques". The latter are the hallmark of this disease. By electron microscopy, several types of amyloid plaques, which corresponded to those seen by PrP immunohistochemistry, were observed. The first type, unicentric "kuru" plaque, consisted of stellate arrangements (stars or cores) of amyloid bundles emanating from a densely interwoven Centre. Amyloid stars were surrounded by astrocytic processes and invaded by microglial cells but dystrophic neurites were only rarely seen. In contrast, multicentric plaques were often surrounded by dystrophic neurites. The rarest type of plaque were neuritic plaques. In 263K- and 22C-H scrapie-infected hamster brains, by light microscopy and semi-thin (1 mum) sections, discrete PrP-immunopositive plaques were observed in the subependymal region but not in the deep brain neuroparenchyma. These plaques were not discernible by routine H & E staining. Ultrastructurally, plaques were recognised as areas of low electron density containing haphazardly-oriented fibrils and not as stellate compact structures typical of plaques in human cases of CJD and GSS. These plaques were located beneath the basal border of the ependymal cells and adjacent blood vessels. Occasional dystrophic neurites containing electron-dense inclusion bodies were seen within the plaque perimeter, which always remained PrP-negative. C1 Med Acad Lodz, Lab Electron Microscopy & Neuropathol, Dept Mol Biol, Chair Oncol, PL-92216 Lodz, Poland. Med Univ Silesia, Chair Mol Biol Biochem & Biopharm, Katowice, Poland. Med Acad Lodz, Dept Tumour Pathol, Chair Oncol, Lodz, Poland. Cent Vet Lab, Lasswade Vet Lab, Edinburgh, Midlothian, Scotland. NINCDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. EM ppliber@csk.am.lodz.pl RI Jeffrey, Martin/D-2251-2009; Kordek, Radzislaw/S-9616-2016 NR 69 TC 5 Z9 5 U1 0 U2 2 PU TERMEDIA PUBLISHING HOUSE LTD PI POZNAN PA WENEDOW ST 9-1, POZNAN, 61-614, POLAND SN 1641-4640 J9 FOLIA NEUROPATHOL JI Folia Neuropathol. PY 2001 VL 39 IS 4 BP 217 EP 235 PG 19 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 512WA UT WOS:000173345500001 PM 11928893 ER PT J AU Buczynski, J Yanagihara, R Mora, C Cartier, L Verdugo, A Araya, F Castillo, L Gibbs, CJ Gajdusek, CD Rogers-Johnson, P Liberski, PP AF Buczynski, J Yanagihara, R Mora, C Cartier, L Verdugo, A Araya, F Castillo, L Gibbs, CJ Gajdusek, CD Rogers-Johnson, P Liberski, PP TI Tropical spastic paraparesis SO FOLIA NEUROPATHOLOGICA LA English DT Review DE HTLV-I; neuroinfection; paraparesis ID VIRUS TYPE-I; CHRONIC PROGRESSIVE MYELOPATHY; SPINAL-CORD LESIONS; HTLV-I; CELLS AB Human T-cell lymphotropic virus type I (HTLV-1) is the cause of endemic tropical spastic paraparesis (TSP) or HTLV-1-associated myelopathy (HAM). Because TSP/HAM is not a fatal disease, the neuropathology of this disease, albeit relatively well understood, is based on the examination of just a few incidental cases. We summarise our experience with the neuropathology of tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). We studied three cases of TSP/HAM from different parts of the world. We demonstrated peculiar lamellated structures, called "multilamellar bodies" (MLB). It is tempting to suggest that MLB may represent specific ultrastructural markers of TSP/HAM. The pathology of the anterior and posterior horns was similar and comprised axonal degeneration, accompanied by extensive astrocytic gliosis. Lymphocytic infiltration, particularly observed as "cuffs" around blood vessels, was scattered among other cellular elements. Ultrastructurally, myelin sheaths were relatively well preserved, and some demyelinated but not remyelinated fibres were observed. Moreover, axons with abnormal accumulations of neurofilaments, suggestive of axonal degeneration, were detected. Several axons contained Hirano bodies. In many samples glial processes replaced most of the remaining neuropil. C1 Med Acad Lodz, Dept Mol Biol, Chair Oncol, Lab Electron Microscopy & Neuropathol, PL-92216 Lodz, Poland. NINCDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. Univ Chile, Dept Neurol Sci, Santiago, Chile. NR 24 TC 1 Z9 1 U1 0 U2 1 PU VIA MEDICA PI GDANSK PA UL SWIETOKRZYSKA 73, 80-180 GDANSK, POLAND SN 1641-4640 J9 FOLIA NEUROPATHOL JI Folia Neuropathol. PY 2001 VL 39 IS 4 BP 265 EP 269 PG 5 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 512WA UT WOS:000173345500006 PM 11928898 ER PT S AU Long, LR Thoma, GR AF Long, LR Thoma, GR GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI Computer assisted retrieval of biomedical image features from spine x-rays: Progress and prospects SO FOURTEENTH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 14th IEEE Symposium on Computer-Based Medical Systems (CBMS 2001) CY JUL 26-27, 2001 CL BETHESDA, MD SP IEEE Comp Soc, Tech Comm Computat Med, NIH, Natl Lib Med, Texas Tech Univ Coll Engn ID VERTEBRAL MORPHOMETRY AB Image indexing for biomedical content is a prohibitively expensive task if done manually, This leads to the demand for effective automated or computer assisted indexing methods. We are doing research on this problem for a set of digitized x-ray films from the second National Health and Nutrition Examination Survey (NHANES II). The 10,000 cervical spine and 7,000 lumbar spine images from this survey are retrievable through a resource we have developed, the Web-based Medical Information Retrieval System (WebMIRS). Using WebMIRS, the user may retrieve x-rays based on text data, such as demographics, health questionnaire responses, or physician's examination results. Two National Institutes of Health workshops have identified visual features of the images specifically, related to osteoarthritis, but the images have never been indexed for these features, which include anterior osteophytes, disc space narrowing, and subluxation. We are investigating the methods by which the indexing and retrieval of the images using these particular features, may be achieved, in a validated manner acceptable to the biomedical community. In this paper we review our work to date, plus the work of collaborating researchers, and present some possible outcomes that appear to be realistic. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Natl Lib Med, Bethesda, MD 20894 USA. EM long@nlm.nih.gov; thoma@nlm.nih.gov NR 17 TC 2 Z9 2 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 2372-9198 BN 0-7695-1004-3 J9 COMP MED SY PY 2001 BP 46 EP 50 DI 10.1109/CBMS.2001.941696 PG 5 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BS87M UT WOS:000171310500009 ER PT S AU Shah, H AF Shah, H GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI Proteus - A model for clinical protocols created from knowledge components SO FOURTEENTH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE COMPUTER-BASED MEDICAL SYSTEMS : PROCEEDINGS OF THE ANNUAL IEEE SYMPOSIUM LA English DT Proceedings Paper CT 14th IEEE Symposium on Computer-Based Medical Systems (CBMS 2001) CY JUL 26-27, 2001 CL BETHESDA, MD SP IEEE Comp Soc, Tech Comm Computat Med, NIH, Natl Lib Med, Texas Tech Univ Coll Engn ID GUIDELINES; RECORD AB We describe a model - Proteus, for clinical protocols created with clinical knowledge represented as components. BY applying principles of distributed computing the knowledge can be managed by experts at other locations while it is available to the clinicians as executable elements for decision support. Editability in the hands of users is essential for the success of any decision support system, A component approach for knowledge along with a notation System for representing the components allows editability, of the protocols by the users. The knowledge components (KCs) also serve as components for an electronic medical record (EMR). Since KCs represent activities within the clinical process, they provide easy way to link components of other clinical or non-clinical processes that are associated or dependent. This provides for extensibility and allows conceiving of integrated information systems that can deal with diverse aspects of healthcare in the Proteus approach. C1 Natl Lib Med, Bethesda, MD USA. RP Shah, H (reprint author), Natl Lib Med, Bethesda, MD USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1063-7125 BN 0-7695-1004-3 J9 COMP MED SY PY 2001 BP 59 EP 64 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BS87M UT WOS:000171310500011 ER PT S AU Yim, PJ Marcos, HB Cloyke, PL Hvizda, JL Libutti, SK Wood, BJ AF Yim, PJ Marcos, HB Cloyke, PL Hvizda, JL Libutti, SK Wood, BJ GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI Detection of blood vessels for radio-frequency ablation treatment planning SO FOURTEENTH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE COMPUTER-BASED MEDICAL SYSTEMS : PROCEEDINGS OF THE ANNUAL IEEE SYMPOSIUM LA English DT Proceedings Paper CT 14th IEEE Symposium on Computer-Based Medical Systems (CBMS 2001) CY JUL 26-27, 2001 CL BETHESDA, MD SP IEEE Comp Soc, Tech Comm Computat Med, NIH, Natl Lib Med, Texas Tech Univ Coll Engn AB Radio-frequency, ablation (RFA) is a minimally invasive image-guided method for local destruction of tumors. Successful ablation, or burning, of tumors, is impeded by bloodflow in the vicinity, of the tumor that tends to cool the tissue. The have developed methods for visualizing the tumors and their spatial relation to blood vessels for the purpose of treatment planning. We apply these methods to hepatic tumors. The visualization method employs contrast-enhanced (Gd-DTPA) magnetic resonance angiography (MRA) and magnetic resonance venography (MRV). The arteries and reins are delineated using the ordered region growing (ORG) skeletonization algorithm. Tumors are contoured manually A shaded surface display is generated that includes the arteries, veins,and tumors. This three-dimensional map will he used to optimize treatment planning and to better limit the effects of perfusion on tumor ablation. A better understanding of the relationship of vessel location, size and flow to thermal lesion could facilitate improved outcomes. C1 Natl Inst Hlth, Imaging Sci Program, Bethesda, MD 20892 USA. RP Yim, PJ (reprint author), Natl Inst Hlth, Imaging Sci Program, Bethesda, MD 20892 USA. NR 8 TC 1 Z9 1 U1 0 U2 1 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1063-7125 BN 0-7695-1004-3 J9 COMP MED SY PY 2001 BP 123 EP 126 DI 10.1109/CBMS.2001.941708 PG 4 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BS87M UT WOS:000171310500021 ER PT S AU Pham, DL AF Pham, DL GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI Robust fuzzy segmentation of magnetic resonance images SO FOURTEENTH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 14th IEEE Symposium on Computer-Based Medical Systems (CBMS 2001) CY JUL 26-27, 2001 CL BETHESDA, MD SP IEEE Comp Soc, Tech Comm Computat Med, NIH, Natl Lib Med, Texas Tech Univ Coll Engn ID BRAIN AB A new approach for robust segmentation of magnetic resonance images is described. The approach is derived that a generalization of the objective function used in Pham and Prince's Adaptive Fuzzy C-means algorithm (AFCM). Within the objective function, an additional constraint is placed on the membership functions that forces them to be spatially smooth. Minimization of this objective function results in an unsupervised fuzzy segmentation algorithm that is robust to both intensity inhomogeniety artifacts as well as noise and other artifacts. The efficacy of the algorithm is demonstrated on simulated magnetic resonance images. C1 NIA, Lab Personal & Cognit, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP NIA, Lab Personal & Cognit, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM dzung.pham@nih.gov NR 7 TC 17 Z9 17 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 2372-9198 BN 0-7695-1004-3 J9 COMP MED SY PY 2001 BP 127 EP 131 PG 5 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BS87M UT WOS:000171310500022 ER PT S AU Hageman, D Reeves, DM AF Hageman, D Reeves, DM GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI Net-Trials (TM) clinical trials information system SO FOURTEENTH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE COMPUTER-BASED MEDICAL SYSTEMS : PROCEEDINGS OF THE ANNUAL IEEE SYMPOSIUM LA English DT Proceedings Paper CT 14th IEEE Symposium on Computer-Based Medical Systems (CBMS 2001) CY JUL 26-27, 2001 CL BETHESDA, MD SP IEEE Comp Soc, Tech Comm Computat Med, NIH, Natl Lib Med, Texas Tech Univ Coll Engn AB The net-Trials (TM) Clinical Trials Information System is an integrated data management system for collecting and reporting data on clinical trials sponsored by the National Cancer Institute's (NCI's) Center for Cancer Research (CCR). Development and implementation of net-Trials is an ongoing process, with the expectation that all functions will be implemented within the next two to three years. As an enabler of clinical research, net-Trials will replace the many stand-alone data management systems used in the past with a single system accessible anytime from anywhere. net-Trials offers numerous benefits to cancer researchers, physicians, and patients, because it it-ill unify systems, processes, and data to facilitate clinical trial participation. net-Trials users will collaborate by transmitting and receiving clinical trials data front a secure central database. C1 Natl Canc Inst, Ctr Canc Res, Off Clin Informat, Bethesda, MD 20892 USA. RP Hageman, D (reprint author), Natl Canc Inst, Ctr Canc Res, Off Clin Informat, Bethesda, MD 20892 USA. NR 5 TC 1 Z9 1 U1 1 U2 1 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1063-7125 BN 0-7695-1004-3 J9 COMP MED SY PY 2001 BP 141 EP 145 PG 5 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BS87M UT WOS:000171310500024 ER PT S AU Moore, DF Pursley, R Altarescu, G Schiffmann, R Dimitriadis, E AF Moore, DF Pursley, R Altarescu, G Schiffmann, R Dimitriadis, E GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI Real time peripheral arterial flow and wall properties derived by pulse waveform analysis and B-mode ultrasound imaging SO FOURTEENTH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE COMPUTER-BASED MEDICAL SYSTEMS : PROCEEDINGS OF THE ANNUAL IEEE SYMPOSIUM LA English DT Proceedings Paper CT 14th IEEE Symposium on Computer-Based Medical Systems (CBMS 2001) CY JUL 26-27, 2001 CL BETHESDA, MD SP IEEE Comp Soc, Tech Comm Computat Med, NIH, Natl Lib Med, Texas Tech Univ Coll Engn AB The development of non-invasive medical technology such cis B-mode ultrasound has allowed direct real time imaging of blood vessels, This enables individual patient arterial responses to be recorded and analyzed following pharmacologic perturbations. By analysis of intra-arterial pressure recordings together with recording of the pulse wave speed, the spatial pressure gradient can be approximated The spatial pressure gradient together with the internal vessel radius from B-mode imaging permits calculation of the vessel volume flow by Womersley analysis, The Womersley solution is the only analytical solution of a time varying flow, which is assumed to be laminar fully developed and Newtonian in an infinitely long rigid tube. We approximated the internal arterial radius by averaging the peak systolic arterial radius and the end diastolic radius following their estimation using a spatial cross-correlation function of the arterial B-mode images. Womersley extended the analysis to elastic tubes and we present illustrative calculations of both the rigid and clastic tube models however, on v the rigid tube model has been experimentally validated. C1 NIH, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. RP Moore, DF (reprint author), NIH, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1063-7125 BN 0-7695-1004-3 J9 COMP MED SY PY 2001 BP 216 EP 221 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BS87M UT WOS:000171310500036 ER PT S AU Kuznetsov, VA Knott, GD AF Kuznetsov, VA Knott, GD GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI A prediction method for multi-class systems based on limited data SO FOURTEENTH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE COMPUTER-BASED MEDICAL SYSTEMS : PROCEEDINGS OF THE ANNUAL IEEE SYMPOSIUM LA English DT Proceedings Paper CT 14th IEEE Symposium on Computer-Based Medical Systems (CBMS 2001) CY JUL 26-27, 2001 CL BETHESDA, MD SP IEEE Comp Soc, Tech Comm Computat Med, NIH, Natl Lib Med, Texas Tech Univ Coll Engn ID PROGNOSIS; CANCER AB In many clinical trials, the prediction of outcome following therapy requires analysis of two or more small groups of responders having a large number of simultaneously measured covariates, some of whose values May be absent. Prediction of individual outcomes in these groups is a severe statistical problem. This lias motivated us to develop a suitable approach for inference from such limited data. A new statistically-oriented prediction method, Optimized Independent Segment Voting (OISV), is presented for constructing a class-membership prediction function for such data sets. This "voting" prediction function is constructed based on the most informative and robust discrete segments of all covariate ranges, which arc thus discretized. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Kuznetsov, VA (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1063-7125 BN 0-7695-1004-3 J9 COMP MED SY PY 2001 BP 279 EP 284 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BS87M UT WOS:000171310500046 ER PT S AU DeLeo, JM Rosenfeld, SJ AF DeLeo, JM Rosenfeld, SJ GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI Important statistical considerations in classifier systems SO FOURTEENTH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE COMPUTER-BASED MEDICAL SYSTEMS : PROCEEDINGS OF THE ANNUAL IEEE SYMPOSIUM LA English DT Proceedings Paper CT 14th IEEE Symposium on Computer-Based Medical Systems (CBMS 2001) CY JUL 26-27, 2001 CL BETHESDA, MD SP IEEE Comp Soc, Tech Comm Computat Med, NIH, Natl Lib Med, Texas Tech Univ Coll Engn AB The performance of a classifier system may be limited due to the following: (1) nonmonotonic relationships between individual predictor cofactors and outcomes, (2) prevalence imbalances between development data and application environment data, and (3) failure to account for cost-gain economics. These issues are explored and statistically-based techniques for treating them are presented. In addition, probabilistic and fuzzy interpretations of classifier outputs are discussed, a likelihood ratio transformation of classifier outputs is suggested, and two new cost-gain indexes that rate classifier systems in global economic terms are introduced. C1 NIH, Dept Clin Res Informat, Ctr Clin, Bethesda, MD 20892 USA. RP DeLeo, JM (reprint author), NIH, Dept Clin Res Informat, Ctr Clin, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1063-7125 BN 0-7695-1004-3 J9 COMP MED SY PY 2001 BP 285 EP 293 PG 9 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BS87M UT WOS:000171310500047 ER PT S AU Le, DX Tran, LQ Chow, J AF Le, DX Tran, LQ Chow, J GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI Automated medical citation records creation for web-based on-line journals SO FOURTEENTH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE COMPUTER-BASED MEDICAL SYSTEMS : PROCEEDINGS OF THE ANNUAL IEEE SYMPOSIUM LA English DT Proceedings Paper CT 14th IEEE Symposium on Computer-Based Medical Systems (CBMS 2001) CY JUL 26-27, 2001 CL BETHESDA, MD SP IEEE Comp Soc, Tech Comm Computat Med, NIH, Natl Lib Med, Texas Tech Univ Coll Engn AB With the rapid expansion and utilization of the Internet and Web technologies, there is an increasing number of On-line medical journals. On-line journals pose new challenges in the areas of automated document analysis and content extraction, database citation records creation, data mining, and other document related applications. New techniques are needed to capture, classify, analyze, extract, modify, and reformat Web-based document information for Computer storage, access, and processing. At the National Library of Medicine (NLM) we are developing an automated system, temporarily code-named WebMARS for Web-Based Medical Article Record System, to create citation records for the MEDLINE (R) database. The system downloads and classifies Web document articles, parses and labels the article contents, extracts and reformats the citation information from the article, presents the entire citation to operators for reconciling (validation), and uploads the citation records to the MEDLINE database. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Le, DX (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 4 TC 6 Z9 6 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1063-7125 BN 0-7695-1004-3 J9 COMP MED SY PY 2001 BP 315 EP 320 DI 10.1109/CBMS.2001.941738 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BS87M UT WOS:000171310500051 ER PT S AU Tran, LQ Moon, CW Le, DX Thoma, GR AF Tran, LQ Moon, CW Le, DX Thoma, GR GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI Web page downloading and classification SO FOURTEENTH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE COMPUTER-BASED MEDICAL SYSTEMS : PROCEEDINGS OF THE ANNUAL IEEE SYMPOSIUM LA English DT Proceedings Paper CT 14th IEEE Symposium on Computer-Based Medical Systems (CBMS 2001) CY JUL 26-27, 2001 CL BETHESDA, MD SP IEEE Comp Soc, Tech Comm Computat Med, NIH, Natl Lib Med, Texas Tech Univ Coll Engn AB This paper describes the processes of downloading and classifying Web-based articles in Online medical journals as a preliminary, step to extracting bibliographic data to populate MEDLINE (R), the widely used database of the National Library, of Medicine (NLM). The processes are combined to develop an automated system named " Web Page Downloading and Classification ". The system downloads the Web pages using Microsoft's Windows Internet API tool called WinInet, and a combination of several Artificial Intelligence (AI) techniques including the Breadth-First search algorithm and the Constraint Satisfaction method. The Breadth-First search algorithm and the Constraint Satisfaction method are then used to traverse the Web page's links, identify these pages as abstract, full text, PDF or image files, recognize and generate the successors of the downloading pages. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Tran, LQ (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1063-7125 BN 0-7695-1004-3 J9 COMP MED SY PY 2001 BP 321 EP 326 DI 10.1109/CBMS.2001.941739 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BS87M UT WOS:000171310500052 ER PT S AU Sansur, CA Eidsath, A DeVroom, HL Ennis, R Heiss, JD AF Sansur, CA Eidsath, A DeVroom, HL Ennis, R Heiss, JD GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI A method to record, store, and analyze multiple physiologic pressure recordings SO FOURTEENTH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE COMPUTER-BASED MEDICAL SYSTEMS : PROCEEDINGS OF THE ANNUAL IEEE SYMPOSIUM LA English DT Proceedings Paper CT 14th IEEE Symposium on Computer-Based Medical Systems (CBMS 2001) CY JUL 26-27, 2001 CL BETHESDA, MD SP IEEE Comp Soc, Tech Comm Computat Med, NIH, Natl Lib Med, Texas Tech Univ Coll Engn ID PATHOPHYSIOLOGY; SYRINGOMYELIA AB To investigate the pathophysiology of syringomyelia, we developed a system to simultaneously record arterial, central venous, airway, cervical subarachnoid, and intrathecal pressures. In addition, our system recorded the electrocardiogram, and provided us with the means to analyze all pressures during individual and averaged cardiac cycles. During the study, flow magnetic resonance imaging and cardiac-gated ultrasound images were also used. To compare our pressure readings with these images we needed to account for the low frequency change in the recorded pressures resulting from normal respiration. We therefore wrote a program to derive mean pressure waves during the cardiac cycle that averaged-out the pressure effects of respiratory cycle. Simultaneous cerebrospinal pressure, hemodynamic pressure, and electrocardiogram were plotted. This allowed us to establish the simultaneous relationship of pressures, syrinx size, and cerebellar tonsil pulsation during the cardiac cycle. This system may prove valuable to other researchers investigating the interaction of multiple physiologic parameters during the cardiac cycle. C1 NINCDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Sansur, CA (reprint author), NINCDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1063-7125 BN 0-7695-1004-3 J9 COMP MED SY PY 2001 BP 343 EP 347 DI 10.1109/CBMS.2001.941743 PG 5 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BS87M UT WOS:000171310500056 ER PT S AU Seckman, C Romano, C Rosenfeld, S AF Seckman, C Romano, C Rosenfeld, S GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI Clinical research protocol mapping: A description of a pilot SO FOURTEENTH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE COMPUTER-BASED MEDICAL SYSTEMS : PROCEEDINGS OF THE ANNUAL IEEE SYMPOSIUM LA English DT Proceedings Paper CT 14th IEEE Symposium on Computer-Based Medical Systems (CBMS 2001) CY JUL 26-27, 2001 CL BETHESDA, MD SP IEEE Comp Soc, Tech Comm Computat Med, NIH, Natl Lib Med, Texas Tech Univ Coll Engn AB Clinical and research activities are focused around protocols. A protocol map is a descriptive, visual tool that outlines all the care events that occur during multiple encounters for a patient over the life of a protocol. The map, which is similar to a clinical pathway, also defines specific interdisciplinary standards of practice and key interventions required to facilitate research and patient outcomes. The inability to aggregate data, retrieve information or generate reports prompted the need to computerize the mapping process. The objectives of the protocol-mapping project were (1) to test the concept of whether research protocol information mapped into a pathway could be automated using pilot software and (2) to determine if an automated protocol map could be used to generate information to project resource utilization volumes. The project was divided into two phases. The implementation of the latter phase of the pilot study incorporated the activities of software development, definition and mapping of pathways for research, collection of clinical data and the generation of reports. Evaluation of the pilot was bused on the accomplishment of the project goals and objectives. The Protocol Hap Pilot vas successful in developing a robust tool for capturing protocol information and generating resource utilization data. The findings from this pilot it-ill be used in developing requirements for a new clinical research information system that it-ill integrate clinical and research information needs. C1 NIH, Bethesda, MD 20892 USA. RP Seckman, C (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1063-7125 BN 0-7695-1004-3 J9 COMP MED SY PY 2001 BP 354 EP 359 DI 10.1109/CBMS.2001.941745 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BS87M UT WOS:000171310500058 ER PT S AU McAuliffe, MJ Lalonde, FM McGarry, D Gandler, W Csaky, K Trus, BL AF McAuliffe, MJ Lalonde, FM McGarry, D Gandler, W Csaky, K Trus, BL GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI Medical Image Processing, Analysis & Visualization in clinical research SO FOURTEENTH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 14th IEEE Symposium on Computer-Based Medical Systems (CBMS 2001) CY JUL 26-27, 2001 CL BETHESDA, MD SP IEEE Comp Soc, Tech Comm Computat Med, NIH, Natl Lib Med, Texas Tech Univ Coll Engn AB Imaging has become an essential component in many fields of medical and laboratory research and clinical practice. Biologists study, cells and generate 3D confocal microscopy datasets, virologists generate 3D reconstructions of viruses from micrographs, radiologists identify and quantify tumors from MRI and CT scans, and neuroscientists detect regional metabolic brain activity from PET and functional MRI scans. Analysis of these diverse image types requires sophisticated computerized quantification and visualisation tools. Until recently, three-dimensional visualization of images and quantitative analysis could only be performed using expensive UNIX workstations and customized software. Today, much of the visualization and analysis can be performed on an inexpensive desktop computer equipped with the appropriate graphics hardware and software, This paper introduces all extensible platform-independent, general-purpose image processing and visualization program specifically designed to meet the needs of a lnternet-linked medical research community. The application named MIPAV (Medical Image Processing Analysis and Visualization) enables clinical and quantitative analysis of medical images over the Internet. Using MIPAV's standard user-interface and analysis tools, researchers and clinicians at remote sites can easily share research data and analyses, thereby enhancing their ability to study, diagnose, monitor, and treat medical disorders. C1 NEI, CBEL, Ctr Informat Technol, NIH, Bethesda, MD 20892 USA. RP NEI, CBEL, Ctr Informat Technol, NIH, Bethesda, MD 20892 USA. EM mcmatt@exchange.nih.gov NR 4 TC 160 Z9 160 U1 1 U2 9 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 2372-9198 BN 0-7695-1004-3 J9 COMP MED SY PY 2001 BP 381 EP 386 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BS87M UT WOS:000171310500062 ER PT S AU Zhao, YD Grover, L Simon, R AF Zhao, YD Grover, L Simon, R GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI TEST: A Web-based T-cell epitope search tool SO FOURTEENTH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE COMPUTER-BASED MEDICAL SYSTEMS : PROCEEDINGS OF THE ANNUAL IEEE SYMPOSIUM LA English DT Proceedings Paper CT 14th IEEE Symposium on Computer-Based Medical Systems (CBMS 2001) CY JUL 26-27, 2001 CL BETHESDA, MD SP IEEE Comp Soc, Tech Comm Computat Med, NIH, Natl Lib Med, Texas Tech Univ Coll Engn AB We here present the web-based tool TEST for searching T-cell epitopes based oil the experimental data from positional scanning synthesized combinatorial libraries (PS-SCL). Implemented with a strong statistical analysis package, relational database and Java applets, the TEST tool first generates scoring matrix, then uses the matrix to scan and score all possible peptides in the user specified protein database. Lob information management functions such as data storage, data retrieval, and data comparison are also provided. The TEST tool has been applied to a variety of T cell clones having known or unknown specificities with reliable predictions, The system should prove useful for the identification of target antigens in infectious diseases, autoimmune disorders, and tumors, and also for the development of vaccines. C1 NCI, Mol Stat & Bioinformat Sect, Biometr Res Branch, Rockville, MD 20852 USA. RP Zhao, YD (reprint author), NCI, Mol Stat & Bioinformat Sect, Biometr Res Branch, Rockville, MD 20852 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1063-7125 BN 0-7695-1004-3 J9 COMP MED SY PY 2001 BP 493 EP 497 DI 10.1109/CBMS.2001.941767 PG 5 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BS87M UT WOS:000171310500079 ER PT S AU Meadows, B Abrams, J Pifer, C Valmonte, C Christian, M Silva, J AF Meadows, B Abrams, J Pifer, C Valmonte, C Christian, M Silva, J GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI The common data element dictionary - A standard nomenclature for the reporting of phase 3 cancer clinical trial data SO FOURTEENTH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE COMPUTER-BASED MEDICAL SYSTEMS : PROCEEDINGS OF THE ANNUAL IEEE SYMPOSIUM LA English DT Proceedings Paper CT 14th IEEE Symposium on Computer-Based Medical Systems (CBMS 2001) CY JUL 26-27, 2001 CL BETHESDA, MD SP IEEE Comp Soc, Tech Comm Computat Med, NIH, Natl Lib Med, Texas Tech Univ Coll Engn AB The Common Data Element (CDE) Dictionary, is an on-line vocabulary repository sponsored by. the National Cancer Institute (NCI). CDEs, a unique language for cancer clinical trials, it-as dei,eloped to standardize the terminology utilized in clinical trials and to promote the uniform collection of study data. By providing a collection of approved terms, investigators in the field can expect that eligibility and data collection requirements for like items it-ill be identical from one trial to the next in a given disease. In addition, CDEs should greatly facilitate data Pooling and comparisons between studies, as analysts will have clear definitions and valid values for like data items. Vith the increasing use of electronic communication, a web- based Dictionary was created to collect and store these data terms in a publicly available site on the, Internet. To create such a CDE Dictionary, consensus on the research and administrative terms was an essential prerequisite. A collaborative effort was initiated by the NCI with experts in a variety of oncology-related disciplines from the Clinical Trials Cooperative Groups along with other trialists to develop the terminology used to collect information specific for cancer clinical trials. Whenever available, terms and values associated with CDEs were chosen based on established standards. Each data clement was also reviewed to see how, it could best be represented in an electronic data collection application that il-as also used to provide an efficient search mechanism within the application. The Cancer Therapy Evaluation Program (CTEP) has implemented the use of CDEs in the development of Case Report Forms (CRFs) used for the collection of clinical trial data on national Phase 3 trials authored by the Clinical Trials Cooperative Groups. All CRFS are reviewed in CTEP to assess usage of the CDEs and staff is available to help those generating CRFs to develop CDEs addressing additional content that reflects the focus of the study. A change management process has been developed for both the content and the database architecture to provide a robust yet stable structure for the Dictionary. This process it-ill also enhance the procedure for submission of new additions to the Dictionary and harmonize suggested changes to CDEs currently available. The goal is to maintain a common nomenclature across modalities and diseases whenever possible to provide consistency in the CDE terminology. C1 NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Meadows, B (reprint author), NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1063-7125 BN 0-7695-1004-3 J9 COMP MED SY PY 2001 BP 498 EP 502 PG 5 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BS87M UT WOS:000171310500080 ER PT S AU Yim, PJ Marcos, HB McAuliffe, M McGarry, D Heaton, I Choyke, PL AF Yim, PJ Marcos, HB McAuliffe, M McGarry, D Heaton, I Choyke, PL GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI Registration of time-series contrast enhanced magnetic resonance images for renography SO FOURTEENTH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE COMPUTER-BASED MEDICAL SYSTEMS : PROCEEDINGS OF THE ANNUAL IEEE SYMPOSIUM LA English DT Proceedings Paper CT 14th IEEE Symposium on Computer-Based Medical Systems (CBMS 2001) CY JUL 26-27, 2001 CL BETHESDA, MD SP IEEE Comp Soc, Tech Comm Computat Med, NIH, Natl Lib Med, Texas Tech Univ Coll Engn ID VALIDATION AB Renovascular disease is an important cause of hypertension. For assessing treatment options for renovascular disease such as angioplasty or nephrectomy, it is important to characterize the renal tissue. Magnetic resonance (MR) renography is becoming a viable method for characterization of the renal tissue. However, analysis of MR renography is hampered by tissue motion. We investigate two automated image registration methods for minimization of the effects of tissue motion. The first is semi-automated registration using contours. The second is an adaption of the Automated Image Registration (AIR) algorithm that accommodates large-scale motion and tissue enhancement from a contrast agent. We compared the results of these methods with manual registration using image overlays. Semi-automated registration using contours accurately registered a 2D MR renography data set of 140 time frames with obvious errors in only 7 slices. With correction in those slices, semi-automatic registration had equivalent quality to manual registration. The adaption of the AIR algorithm produced better results on 3D MR renography in healthy kidneys than manual registration but worse results in a diseased kidney. We conclude that automated registration of 2D and 3D MR renography is feasible. C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Yim, PJ (reprint author), NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1063-7125 BN 0-7695-1004-3 J9 COMP MED SY PY 2001 BP 516 EP 520 PG 5 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BS87M UT WOS:000171310500083 ER PT S AU Buck, GM Schuster, JHR Vena, JE Weiner, JM AF Buck, GM Schuster, JHR Vena, JE Weiner, JM GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI Web-based data capture and management in epidemiologic investigations SO FOURTEENTH IEEE SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS, PROCEEDINGS SE COMPUTER-BASED MEDICAL SYSTEMS : PROCEEDINGS OF THE ANNUAL IEEE SYMPOSIUM LA English DT Proceedings Paper CT 14th IEEE Symposium on Computer-Based Medical Systems (CBMS 2001) CY JUL 26-27, 2001 CL BETHESDA, MD SP IEEE Comp Soc, Tech Comm Computat Med, NIH, Natl Lib Med, Texas Tech Univ Coll Engn ID WORLD-WIDE-WEB; INTERNET AB Database management is an important aspect of epidemiologic studies requiring understanding of the scientific problems under investigation cis well as a clear understanding of the formal data processing required. Failure to achieve this combination is not a rare event. To address this deficit, a database management process was designed that allowed the epidemiologist investigator to focus entirely on the survey or data capture instrument to be employed in the study. As that document is prepared, the database management is automatically constructed so that there are no interpretative errors. This approach has been prepared in two formats, both designed to function at the Internet. These are the Data Base Research DBR) system and the Simplified Survey System (S3). C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA. RP Buck, GM (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, 6100 Bldg,Room B703,6100 Execut Blvd, Rockville, MD 20852 USA. OI Buck Louis, Germaine/0000-0002-1774-4490 NR 6 TC 0 Z9 0 U1 0 U2 1 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1063-7125 BN 0-7695-1004-3 J9 COMP MED SY PY 2001 BP 547 EP 552 DI 10.1109/CBMS.2001.941776 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BS87M UT WOS:000171310500088 ER PT J AU Arimoto, T Nguyen, X Sato, K Mason, RP Bing, GY AF Arimoto, T Nguyen, X Sato, K Mason, RP Bing, GY TI Up-regulation of inducible nitric oxide synthase in the snbstantia nigra by lipopolysaccharide causes microglial activation, resulting in neurodegeneration SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIEHS, Free Rad Metabolite Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. RI Nguyen, Xuan/G-5532-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 111 BP S44 EP S44 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200127 ER PT J AU Arimoto, T Sato, K Kadiiska, MB Corbett, J Mason, RP AF Arimoto, T Sato, K Kadiiska, MB Corbett, J Mason, RP TI In vivo evidence of free radical production in paraquat-induced lung injury using ESR spin trap method SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIEHS, Free Radical Metabolite Sect, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 39 BP S22 EP S22 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200055 ER PT J AU Belanger, AG Bilski, P Chignell, CF AF Belanger, AG Bilski, P Chignell, CF TI Photosensitized oxidation of 2,7-dichlorofluorescin SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIEHS, Chem & Pharmacol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 359 BP S120 EP S120 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200375 ER PT J AU Bilski, P Wolak, M Zhang, V Chignell, CF Moore, DE AF Bilski, P Wolak, M Zhang, V Chignell, CF Moore, DE TI Singlet oxygen and free radical species are involved in phototoxicity of anti-convulsant drug lamotrigine SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIEHS, Lab Pharmacol Chem, Res Triangle Pk, NC 27709 USA. Univ Sydney, Dept Pharm, Sydney, NSW 2006, Australia. NR 0 TC 0 Z9 0 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 360 BP S120 EP S120 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200377 ER PT J AU Bonini, MG Mason, RP Augusto, O AF Bonini, MG Mason, RP Augusto, O TI Tempol (4-hydroxy-2,2,6,6-tetramethyilpiperidene-1-oxyl) diverts peroxynitrite decomposition from nitrating to nitrosylating species SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Univ Sao Paulo, Inst Quim, Sao Paulo, Brazil. NIEHS, Res Triangle Pk, NC 27709 USA. RI Augusto, Ohara/D-3839-2012 OI Augusto, Ohara/0000-0002-7220-4286 NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 225 BP S77 EP S77 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200241 ER PT J AU Bradbury, CM Spitz, DR Gius, D AF Bradbury, CM Spitz, DR Gius, D TI Thioredoxin reductase is a novel cytoplasmic signaling factor regulating radiation-induced AP-1 DNA-binding activity and gene expression via active cysteine residues SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NCI, ROSP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 381 BP S128 EP S128 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200398 ER PT J AU Chen, YR Deterding, LJ Sturgeon, LJ Tomer, BE Mason, RP AF Chen, YR Deterding, LJ Sturgeon, LJ Tomer, BE Mason, RP TI Protein oxidation of mitochondrial cytochrome c (cyt c) by reactive halogen species (RHS) enhances its peroxidase properties SO FREE RADICAL BIOLOGY AND MEDICINE 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 PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 251 BP S84 EP S84 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200267 ER PT J AU Chignell, CF Sik, RH AF Chignell, CF Sik, RH TI Photochemical study of keratinocytes loaded with 2 ',7 '-dichlorofluorescin: Implications for the detection of reactive oxygen species generated during UVA irradiation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 362 BP S120 EP S120 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200378 ER PT J AU Dikalov, SI Vitek, MP Mason, RP AF Dikalov, SI Vitek, MP Mason, RP TI Cupric-amyloid b peptide complexes stimulate oxidation of ascorbate and generation of OH- radials SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Emory Univ, Sch Med, Div Cardiol, FRIMCORE, Atlanta, GA 30322 USA. Duke Univ, Med Ctr, Dept Med, Div Neurol, Durham, NC 27710 USA. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 391 BP S131 EP S131 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200407 ER PT J AU Espey, MG Xavier, S Thomas, DD Miranda, KM Wink, DA AF Espey, MG Xavier, S Thomas, DD Miranda, KM Wink, DA TI Direct real-time evaluation of protein nitration in solution and within human cells reveals the impact nitrogen dioxide over peroxynitrite mechanisms SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIH, NCI, RBB, Bethesda, MD 20892 USA. RI Miranda, Katrina/B-7823-2009 NR 0 TC 0 Z9 0 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 229 BP S78 EP S78 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200245 ER PT J AU Gius, D Bradbury, CM AF Gius, D Bradbury, CM TI Indomethacin-induced radiosensitization and inhibition of ionizing radiation-induced NF-kappa B activation in HeLa cells occur via a mechanism involving p38 MAP kinase SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIH, NCI, ROSP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 147 BP S54 EP S54 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200163 ER PT J AU Guo, Q Corbett, JT Fann, YC Qian, SY Mason, RP AF Guo, Q Corbett, JT Fann, YC Qian, SY Mason, RP TI Electron spin resonance investigation of semiquinone radicals formed from the reaction of ubiquinone 0 with human oxyhemoglobin SO FREE RADICAL BIOLOGY AND MEDICINE 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 PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 26 BP S18 EP S18 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200044 ER PT J AU Harris, CC AF Harris, CC TI Gene-environment interactions in human cancer risk SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA P10 BP S6 EP S6 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200011 ER PT J AU Inbaraj, JJ Sik, RH Chignell, CF AF Inbaraj, JJ Sik, RH Chignell, CF TI Oxidative stress induced by juglone (5-hydroxy-1,4-naphthoquinone) - A component of black walnut SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIEHS, Chem & Pharmacol Lab, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 281 BP S93 EP S93 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200297 ER PT J AU Ingram, JL Rice, AB Tabor, MB Bonner, JC AF Ingram, JL Rice, AB Tabor, MB Bonner, JC TI Metal- and oxidant-induced p38 MAP kinase activation mediates HB-EGF expression in human lung fibroblasts SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIEHS, Pulm Pathobiol Lab, Airway Inflammat Grp, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 154 BP S55 EP S55 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200170 ER PT J AU Kadiiska, MB Gladen, BC Baird, DB Tomer, KB Mason, RP Barrett, JC AF Kadiiska, MB Gladen, BC Baird, DB Tomer, KB Mason, RP Barrett, JC TI Biomarkers of oxidative stress study: Are oxidation products of lipids, proteins and DNA markers in CCl4 poisoning? SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 261 BP S87 EP S87 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200278 ER PT J AU Kaushal, A Bisht, KS Bradbury, CM Gius, D AF Kaushal, A Bisht, KS Bradbury, CM Gius, D TI AP-1 activation of DNA methyltransferase contributes to a unique multi-modality resistant phenotype via cellular oxidative stress responses SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NCI, ROSP, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 156 BP S56 EP S56 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200173 ER PT J AU Kuppusamy, P Li, HQ Ilangovan, O Cardounel, AJ Zweier, JL Mitchell, JB AF Kuppusamy, P Li, HQ Ilangovan, O Cardounel, AJ Zweier, JL Mitchell, JB TI In vivo imaging of tumor redox status: Effect of GSH depletion SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Johns Hopkins Univ, Dept Med, EPR Ctr, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 413 BP S139 EP S139 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200429 ER PT J AU Kuppusamy, P Ilangovan, G Li, HQ Zweier, JL Mitchell, JB AF Kuppusamy, P Ilangovan, G Li, HQ Zweier, JL Mitchell, JB TI Alterations in systemic and tumor tissue oxygenation as a function of tumor growth SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 415 BP S139 EP S139 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200430 ER PT J AU Landmesser, U Dikalov, S McCann, L Holland, SM Mitch, WE Harrison, DG AF Landmesser, U Dikalov, S McCann, L Holland, SM Mitch, WE Harrison, DG TI Mechanisms underlying uncoupling of endothelial cell nitric oxide synthase in hypertension SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Emory Univ, Div Cardiol, Sch Med, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Div Renal, Atlanta, GA 30322 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 206 BP S70 EP S70 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200221 ER PT J AU Lin, X Spitz, DR Gius, D AF Lin, X Spitz, DR Gius, D TI Cytotoxic and radiosensitizing effects of 2-Deoxy-D-glucose on HeLa cells involves oxidative stress SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Univ Iowa, NCI, NIH, Free Rad & Radiat Biol Program, Iowa City, IA 52242 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 342 BP S112 EP S112 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200357 ER PT J AU Miranda, KM Espey, MG Paolocci, N Bartberger, MD Colton, CA Wink, DA AF Miranda, KM Espey, MG Paolocci, N Bartberger, MD Colton, CA Wink, DA TI The chemistry of nitroxyl (HNO) and implications in various therapeutic applications. SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Biomed Engn, Baltimore, MD 21205 USA. Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90024 USA. Duke Univ, Med Ctr, Dept Neurol, Durham, NC USA. RI Miranda, Katrina/B-7823-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 212 BP S72 EP S72 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200228 ER PT J AU Moskovitz, J Bar-Noy, S Williams, WM Jesus, R Berlett, BS Stadtman, ER AF Moskovitz, J Bar-Noy, S Williams, WM Jesus, R Berlett, BS Stadtman, ER TI Peptide-methionine sulfoxide reductase (MsrA) knock out mic are short lived and hyper-sensitive to oxidative stress. SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIH, Biochem Lab, NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 265 BP S88 EP S88 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200282 ER PT J AU Qian, SY Mason, RP AF Qian, SY Mason, RP TI A novel approach characterizes the radicals formed in lipid peroxidation: Optimization of chromatography assists radical adduct identification with ESR spin-trapping and mass spectrometry SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 12 BP S13 EP S13 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200029 ER PT J AU Qian, SY Guo, Q Yue, GH Tomer, KB Mason, RP AF Qian, SY Guo, Q Yue, GH Tomer, KB Mason, RP TI Modification of liquid chromatography/electron spin resonance and mass spectrometry allows reliable identification of radical adducts formed from soybean lipoxygenase-derived peroxidation of polyunsaturated fatty acids SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 13 BP S14 EP S14 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200030 ER PT J AU Reiter, CD Cannon, RO Schechter, AN Gladwin, MT AF Reiter, CD Cannon, RO Schechter, AN Gladwin, MT TI Sickle cell anemia is characterized by a deficiency of circulating plasma S-nitrosothiols and by NO scavenging by plasma heme. SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 215 BP S72 EP S72 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200231 ER PT J AU Samuni, AM Chuang, YE DeGraff, W Russo, A Krishna, MC Mitchell, JB AF Samuni, AM Chuang, YE DeGraff, W Russo, A Krishna, MC Mitchell, JB TI Catecholic estrogen mediated mutagenesis and carcinogenesis: Chemoprevention strategies with antioxidants SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NCI, RBB, DCS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 15 BP S14 EP S14 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200031 ER PT J AU Sato, K Arimoto, T Kadiiska, MB Corbett, J Fann, YC Detweiler, C Mason, RP AF Sato, K Arimoto, T Kadiiska, MB Corbett, J Fann, YC Detweiler, C Mason, RP TI In vivo direct evidence of free radical formation in rat pneumonia model induced by Pseudomonas aeruginosa SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIEHS, Free Rad Metabolite Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 136 BP S50 EP S50 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200153 ER PT J AU Sato, K Kadiiska, MB Ghio, AJ Corbett, J Fann, YC Holland, SM Thurman, RG Mason, RP AF Sato, K Kadiiska, MB Ghio, AJ Corbett, J Fann, YC Holland, SM Thurman, RG Mason, RP TI In vivo radical formation by NADPH oxidase in lung induced by lipopolysaccharide a model for ARDS SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. US EPA, Washington, DC 20460 USA. NIAID, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 135 BP S50 EP S50 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200151 ER PT J AU Thomas, DD Espey, MG Miranda, K Wink, DA AF Thomas, DD Espey, MG Miranda, K Wink, DA TI Nitrogen dioxide and nitrous anhydride are the most important nitrating and nitrosating species: a comparison. SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RI Miranda, Katrina/B-7823-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 17 BP S15 EP S15 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200034 ER PT J AU Tsuchiya, K Kirima, K Yoshizumi, M Houchi, H Tamaki, T Mason, RP AF Tsuchiya, K Kirima, K Yoshizumi, M Houchi, H Tamaki, T Mason, RP TI NO-forming reactions of the iron-MGD complex with thiols and nitrosothiol compounds SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Univ Tokushima, Sch Med, Dept Pharmacol, Tokushima 7708503, Japan. Univ Tokushima, Sch Med, Dept Pharm, Tokushima 7708503, Japan. NIEHS, LPC, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 246 BP S82 EP S82 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200263 ER PT J AU van der Veen, RC Dietlin, TA Holland, SM Hofman, FM AF van der Veen, RC Dietlin, TA Holland, SM Hofman, FM TI Severe encephalitis in NADPH-oxidase KO mice by adoptive transfer: NO and O2-regulate immune intensity SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Univ So Calif, Los Angeles, CA 90089 USA. NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 219 BP S73 EP S73 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200235 ER PT J AU Wang, YZ Bonner, JC AF Wang, YZ Bonner, JC TI Differential mechanism of STAT-1 activation by hydrogen peroxide and vanadium pentoxide SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NIEHS, LPP, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA 187 BP S64 EP S64 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200203 ER PT J AU Wink, DA AF Wink, DA TI Chemical biology of reactive oxygen and nitrogen metabolites: Implications in cancer SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2001 VL 31 SU 1 MA P9 BP S6 EP S6 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 491EZ UT WOS:000172096200010 ER PT J AU Bar-Noy, S Gorlatov, SN Stadtman, TC AF Bar-Noy, S Gorlatov, SN Stadtman, TC TI Overexpression of wild type and SeCys/Cys mutant of human thioredoxin reductase in E-coli: The role of selenocysteine in the catalytic activity SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE thioredoxin reductase; selenoprotein; selenocysteine; SECIS element; expression; free radicals ID LUNG ADENOCARCINOMA CELLS; ESCHERICHIA-COLI; GLUTATHIONE-REDUCTASE; HELA-CELLS; INSERTION-SEQUENCE; MESSENGER-RNA; PURIFICATION; MECHANISM; HEPARIN; DEHYDROGENASE AB In contrast to Escherichia coli and yeast thioredoxin reductases, the human placental enzyme contains an additional redox center consisting of a cysteine-selenocysteine pair that precedes the C-terminal glycine residue. This reactive selenocysteine-containing center imbues the enzyme with its unusually wide substrate specificity. For expression of the human gene in E. coli. the sequence corresponding to the SECIS element required for selenocysteine insertion in E. coli formate dehydrogenase H was inserted downstream of the TC;A codon in the human thioredoxin reductase gene. Omission of this SECIS element from another construct resulted in termination at UGA. Change of the TGA codon to TGT gave a mutant enzyme form in which selenocysteine was replaced with cysteine. The three gene products were purified using a standard isolation protocol. Binding properties of the three proteins to the affinity resins used for purification and to NADPH were similar. The three proteins occurred as dimers in the native state and exhibited characteristic thiolate-flavin charge transfer spectra upon reduction. With DTNB as substrate, compared to native rat liver thioredoxin reductase, catalytic activities were 16% for the recombinant wild type enzyme, about 5% for the cysteine mutant enzyme, and negligible fur the truncated enzyme form. (C) 2000 Elsevier Science Inc. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, TC (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3,Room 108,MSC-0320 Ctr Dr, Bethesda, MD 20892 USA. NR 28 TC 32 Z9 32 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JAN 1 PY 2001 VL 30 IS 1 BP 51 EP 61 DI 10.1016/S0891-5849(00)00448-2 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 387PB UT WOS:000166130000006 PM 11134895 ER PT J AU Gladwin, MT Ognibene, FP Shelhamer, JH Pease-Fye, ME Noguchi, CT Rodgers, GP Schechter, AN AF Gladwin, MT Ognibene, FP Shelhamer, JH Pease-Fye, ME Noguchi, CT Rodgers, GP Schechter, AN TI Nitric oxide transport on sickle cell hemoglobin: Where does it bind? SO FREE RADICAL RESEARCH LA English DT Article ID S-NITROSOHEMOGLOBIN; OXYGEN-BINDING; BLOOD-FLOW; NO; OXYHEMOGLOBIN; ERYTHROCYTES; NITROSATION; INHIBITION; AFFINITY; INCREASE AB We have recently reported that nitric oxide inhalation in individuals with sickle cell anemia increases the level of NO bound to hemoglobin, with the development of an arterial-venous gradient, suggesting delivery to the tissues. A recent model suggests that nitric oxide, in addition to its well-known reaction with heme groups, reacts with the beta -globin chain cysteine 93 to form S-nitrosohemoglobin (SNO-Hb) and that SNO-Hb would preferentially release nitric oxide in the tissues and thus modulate blood flow. However, we have also recently determined that the primary NO hemoglobin adduct formed during NO breathing in normal (hemoglobin A) individuals is nitrosyl (heme)hemoglobin (HbFe(II)NO), with only a small amount of SNO-Hb formation. To determine whether the NO is transported as HbFe(II)NO or SNO-Hb in sickle cell individuals, which would have very different effects on sickle hemoglobin polymerization, we measured these two hemoglobin species in three sickle cell volunteers before and during a dose escalation of inhaled NO (40, 60, and 80 ppm). Similar to our previous observations in normal individuals, the predominant species formed was HbFe(II)NO, with a significant arterial-venous gradient. Minimal SNO-Hb was formed during NO breathing, a finding inconsistent with significant transport of NO using this pathway, but suggesting that this pathway exists. These results suggest that NO binding to heme groups is physiologically a rapidly reversible process, supporting a revised model of hemoglobin delivery of NO in the peripheral circulation and consistent with the possibility that NO delivery by hemoglobin may be therapeutically useful in sickle cell disease. C1 NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Gladwin, MT (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 25 TC 9 Z9 9 U1 0 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2001 VL 35 IS 2 BP 175 EP 180 DI 10.1080/10715760100300721 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 458XE UT WOS:000170220100010 PM 11697198 ER PT J AU Demehin, AA Abugo, OO Rifkind, JM AF Demehin, AA Abugo, OO Rifkind, JM TI The reduction of nitroblue tetrazolium by Red Blood Cells: a measure of red cell membrane antioxidant capacity and hemoglobin-membrane binding sites SO FREE RADICAL RESEARCH LA English DT Article DE antioxidant capacity; Red Blood Cells; membrane; nitroblue tetrazolium; hemoglobin; antioxidant; vitamin E (alpha-tocopherol); vitamin C (ascorbic acid) ID HUMAN-ERYTHROCYTE MEMBRANE; PHOSPHOLIPID ASYMMETRY; SUPEROXIDE-DISMUTASE; LIPID-PEROXIDATION; ALPHA-TOCOPHEROL; BAND-3; PLASMA; ASCORBATE; SYSTEM; EQUILIBRIUM AB The reduction of nitroblue tetrazolium (NBT) with intact Red Blood Cells (RBCs) is biphasic with an initial rapid reduction followed by a slower second phase. This biphasic kinetics has been explained with the initial rapid phase attributed to antioxidants in the red cell which reduce membrane bound NBT and the slower phase associated with the reaction of NBT with membrane bound hemoglobin. This model has been confirmed by a utilization of a number of red cell modifications which either increase the red cell antioxidants (vitamin C and vitamin E) or damage the red cell membrane (cumene hydroperoxide and N-ethylmaleimide). The utilization of this assay for human blood samples was investigated by studying a series of 20 human subjects ranging between 34 and 87 years of age. It was possible to fit all of these samples with two adjustable parameters which reflect the red cell membrane antioxidant capacity (x) and the hemoglobin membrane interactions (m). The antioxidant capacity shows a significant (p <.002; R = -.67) decrease with age. This finding is consistent with a decrease in the level of antioxidants in aged subjects. In addition, the number of hemoglobin membrane sites are negatively correlated with the antioxidant capacity (p <.02; R = -.52) suggesting that the oxidative stress associated with reduced antioxidants results in increased hemoglobin-membrane interactions. C1 NIA, Mol Dynam Sect, Cellular & Mol Biol Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Rifkind, JM (reprint author), NIA, Mol Dynam Sect, Cellular & Mol Biol Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 44 TC 14 Z9 14 U1 1 U2 2 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2001 VL 34 IS 6 BP 605 EP 620 DI 10.1080/10715760100300501 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 461VT UT WOS:000170384700004 PM 11697036 ER PT S AU Wilson, CG Butera, RJ Del Negro, CA Rinzel, J Smith, JC AF Wilson, CG Butera, RJ Del Negro, CA Rinzel, J Smith, JC BE Poon, CS Kasemi, H TI Interfacing computer models with real neurons: Respiratory "cyberneurons" created with the dynamic clamp SO FRONTIERS IN MODELING AND CONTROL OF BREATHING: INTERGATION AT MOLECULAR, CELLULAR, AND SYSTEMS LEVELS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 8th International Oxford Conference on Frontiers in Modeling and Control of Breathing CY OCT 11-15, 2000 CL N FALMOUTH, MASSACHUSETTS SP Amer Physiol Soc, Physiol Soc, Whitaker Fdn, Respirat Physiol, GlaxosmithKline Inc, Harvard Apparatus Inc, Amer Thorac Soc ID RHYTHM C1 NINCDS, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA. Georgia Inst Technol, Inst Bioengn & Biosci, Atlanta, GA 30332 USA. NYU, Ctr Neural Sci, New York, NY 10013 USA. NYU, Courant Inst Math Sci, New York, NY 10013 USA. RP Wilson, CG (reprint author), NINCDS, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA. OI Butera, Robert/0000-0002-1806-0621 NR 8 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46647-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2001 VL 499 BP 119 EP 124 PG 6 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental; Neurosciences; Respiratory System SC Biochemistry & Molecular Biology; Research & Experimental Medicine; Neurosciences & Neurology; Respiratory System GA BT28T UT WOS:000172534500019 PM 11729865 ER PT S AU Del Negro, CA Wilson, CG Butera, RJ Koshiya, N Johnson, SM Smith, JC AF Del Negro, CA Wilson, CG Butera, RJ Koshiya, N Johnson, SM Smith, JC BE Poon, CS Kasemi, H TI Unstable breathing rhythms and quasiperiodicity in the pre-Botzinger complex SO FRONTIERS IN MODELING AND CONTROL OF BREATHING: INTERGATION AT MOLECULAR, CELLULAR, AND SYSTEMS LEVELS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 8th International Oxford Conference on Frontiers in Modeling and Control of Breathing CY OCT 11-15, 2000 CL N FALMOUTH, MASSACHUSETTS SP Amer Physiol Soc, Physiol Soc, Whitaker Fdn, Respirat Physiol, GlaxosmithKline Inc, Harvard Apparatus Inc, Amer Thorac Soc ID RESPIRATORY RHYTHM; PACEMAKER NEURONS; GENERATION; MODELS C1 NINCDS, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA. Georgia Inst Technol, Inst Bioengn & Biosci, Atlanta, GA 30332 USA. RP Del Negro, CA (reprint author), NINCDS, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA. OI Butera, Robert/0000-0002-1806-0621 NR 11 TC 0 Z9 0 U1 0 U2 1 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46647-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2001 VL 499 BP 133 EP 138 PG 6 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental; Neurosciences; Respiratory System SC Biochemistry & Molecular Biology; Research & Experimental Medicine; Neurosciences & Neurology; Respiratory System GA BT28T UT WOS:000172534500021 PM 11729867 ER PT S AU Rigatto, H Wilson, CG Koshiya, N House, S Smith, JC AF Rigatto, H Wilson, CG Koshiya, N House, S Smith, JC BE Poon, CS Kasemi, H TI Stationary organotypic culture of the pre-Botzinger complex from the newborn rat SO FRONTIERS IN MODELING AND CONTROL OF BREATHING: INTERGATION AT MOLECULAR, CELLULAR, AND SYSTEMS LEVELS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 8th International Oxford Conference on Frontiers in Modeling and Control of Breathing CY OCT 11-15, 2000 CL N FALMOUTH, MASSACHUSETTS SP Amer Physiol Soc, Physiol Soc, Whitaker Fdn, Respirat Physiol, GlaxosmithKline Inc, Harvard Apparatus Inc, Amer Thorac Soc ID CENTRAL RESPIRATORY NEURONS; SPINAL-CORD; SEARCH C1 NINCDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. Univ Manitoba, Dept Pediat & Physiol, Winnipeg, MB R3E 0L8, Canada. NINCDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Rigatto, H (reprint author), NINCDS, Neural Control Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 13 TC 1 Z9 1 U1 0 U2 1 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46647-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2001 VL 499 BP 139 EP 145 PG 11 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental; Neurosciences; Respiratory System SC Biochemistry & Molecular Biology; Research & Experimental Medicine; Neurosciences & Neurology; Respiratory System GA BT28T UT WOS:000172534500022 PM 11729868 ER PT S AU Burke, RE AF Burke, RE BE Ruzicka, E Hallett, M Jankovic, J TI The central pattern generator for locomotion in mammals SO GAIT DISORDERS SE ADVANCES IN NEUROLOGY LA English DT Article; Proceedings Paper CT International Symposium on Gait Disorders CY SEP, 1999 CL PRAGUE, CZECH REPUBLIC SP Movement Disorder Soc ID MEDULLARY RETICULOSPINAL NEURONS; LATENCY CUTANEOUS EXCITATION; DISTAL HINDLIMB MUSCULATURE; DEPENDENT REFLEX REVERSAL; FICTIVE LOCOMOTION; SPINAL-CORD; VENTRAL SPINOCEREBELLAR; ELECTRICAL-STIMULATION; HUMAN WALKING; CAT HINDLIMB C1 NINCDS, Lab Neural Control, NIH, Bethesda, MD 20892 USA. RP NINCDS, Lab Neural Control, NIH, Bethesda, MD 20892 USA. NR 72 TC 23 Z9 23 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0091-3952 BN 0-7817-2123-7 J9 ADV NEUROL JI Adv.Neurol. PY 2001 VL 87 BP 11 EP 24 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BT95F UT WOS:000174575800002 PM 11347213 ER PT S AU Hallett, M AF Hallett, M BE Ruzicka, E Hallett, M Jankovic, J TI Cerebellar ataxic gait SO GAIT DISORDERS SE ADVANCES IN NEUROLOGY LA English DT Article; Proceedings Paper CT International Symposium on Gait Disorders CY SEP, 1999 CL PRAGUE, CZECH REPUBLIC SP Movement Disorder Soc ID ABNORMAL CONTROL; MOVEMENT; INFORMATION; DEFICITS C1 NINCDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINCDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NR 24 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0091-3952 BN 0-7817-2123-7 J9 ADV NEUROL JI Adv.Neurol. PY 2001 VL 87 BP 155 EP 163 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BT95F UT WOS:000174575800015 PM 11347218 ER PT B AU Patton, JT AF Patton, JT BE Chadwick, D Goode, JA TI Rotavirus RNA replication and gene expression SO GASTROENTERITIS VIRUSES SE NOVARTIS FOUNDATION SYMPOSIUM LA English DT Article; Proceedings Paper CT Symposium on Gastroenteritis Viruses CY MAY 16-18, 2000 CL NOVARTIS FDN, LONDON, ENGLAND HO NOVARTIS FDN ID 3'-TERMINAL CONSENSUS SEQUENCE; INFLUENZA-VIRUS POLYMERASE; MINUS-STRAND SYNTHESIS; MESSENGER-RNA; VIRAL-RNA; TRANSLATION INITIATION; GENOME REARRANGEMENTS; BINDING-PROTEIN; OPEN CORES; NSP5 AB Rotavirus mRNAs are capped but non-polyadenylated and serve as templates for both the synthesis of viral proteins and the segmented dsRNA genome. Vital proteins involved in RNA replication include the RNA polymerase (VP1), the core scaffold protein (VP2) and the non-structural RNA-binding proteins (NSP2 and NSP5). VP2 enhances dsRNA synthesis in vitro, possibly by forming platform structures on which VP1 functions. NSP2 octamers have NTPase and helix-destabilizing activity, and in conjunction with the phosphoprotein NSP5, are proposed to facilitate RNA packaging. The structure of the mRNA template contributes importantly to RNA replication. In particular, base-pairing between the 5' and 3'-ends of viral mRNA generates panhandle structures which promote minus-strand synthesis. For the group A rotaviruses, the 3'-consensus sequence, 5'-UGUGACC-3', which extends as a 3'-tail from the panhandles, also contributes to efficient minus-strand synthesis. Besides containing cis-acting replication signals, the 3'-end of viral mRNAs contains information that stimulates gene expression in infected cells. Specifically, the last four nucleotides of the 3'-consensus sequence, 5'-GACC-3', operate as a virus-specific translation enhancer (3'TE) via a process thought to involve recognition of the element by NSP3. The NSP3-3'TE complex may mimic the function of complexes formed by eukaryotic poly(A)-tails and poly(A)-binding protein, thereby promoting more efficient translation of viral mRNAs. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 6 Ctr Dr,MSC 0720,Rm 117, Bethesda, MD 20892 USA. RI Patton, John/P-1390-2014 NR 54 TC 24 Z9 25 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA BAFFINS LANE, CHICHESTER PO19 1UD, WEST SUSSEX, ENGLAND BN 0-471-49663-4 J9 NOVART FDN SYMP PY 2001 VL 238 BP 64 EP 81 PG 18 WC Gastroenterology & Hepatology; Medicine, General & Internal; Virology SC Gastroenterology & Hepatology; General & Internal Medicine; Virology GA BS91F UT WOS:000171368200005 PM 11444036 ER PT B AU Kapikian, AZ AF Kapikian, AZ BE Chadwick, D Goode, JA TI A rotavirus vaccine for prevention of severe diarrhoea of infants and young children: development, utilization and withdrawal SO GASTROENTERITIS VIRUSES SE NOVARTIS FOUNDATION SYMPOSIUM LA English DT Article; Proceedings Paper CT Symposium on Gastroenteritis Viruses CY MAY 16-18, 2000 CL NOVARTIS FDN, LONDON, ENGLAND HO NOVARTIS FDN ID INTUSSUSCEPTION; INFECTION; EFFICACY; SAFETY; GASTROENTERITIS; CHILDHOOD; SEROTYPES; BOVINE; TRIAL; ENTRY AB The importance of rotaviruses (RVs) as the single most important cause of severe diarrhoea of infants and young children is well recognized. At NIH, we developed a quadrivalent (tetravalent [TV]) vaccine to protect against the four epidemiologically important RV serotypes. It is comprised of live attenuated rhesus. RV (RRV), a VP7 serotype G3 strain (the 'Jennerian' approach), and three reassortant RVs, each containing 10 RRV genes and one human RV gene that codes for the major outer protein, VP7, that determines serotype G1, G2 or G4 specificity (the 'modified Jennerian' approach). The vaccine was safe and effective against severe diarrhoea in a major pre-licensure collaborative effort of phase III trials. In February 1998 and again in June 1998, the Advisory Committee on Immunization Practices (ACIP) recommended routine immunization with three oral doses at 2, 4 and 6 months of age. The tetravalent vaccine (RotaShield) was licensed in the USA by the FDA in August 1998. In July 1999, after about 1.5 million doses had been given, the CDC recommended suspending administration of the vaccine because post-licensure surveillance of adverse events had suggested an association with intussusception. After further investigation by CDC, in October 1999, the ACIP withdrew its recommendation concluding that '... intussusception occurs with significantly increased frequency in the first 1-2 weeks after vaccination with RRV-TV, particularly following the first dose'. The implications of these developments from a practical, epidemiological, analytical and ethical perspective are discussed. C1 NIAID, Lab Infect Dis, Epidemiol Sect, NIH, Bethesda, MD 20852 USA. RP Kapikian, AZ (reprint author), NIAID, Lab Infect Dis, Epidemiol Sect, NIH, Bethesda, MD 20852 USA. NR 33 TC 45 Z9 49 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA BAFFINS LANE, CHICHESTER PO19 1UD, WEST SUSSEX, ENGLAND BN 0-471-49663-4 J9 NOVART FDN SYMP PY 2001 VL 238 BP 153 EP 179 PG 27 WC Gastroenterology & Hepatology; Medicine, General & Internal; Virology SC Gastroenterology & Hepatology; General & Internal Medicine; Virology GA BS91F UT WOS:000171368200009 PM 11444025 ER PT J AU Lynch, MA Petrel, TA Song, H Knobloch, TJ Casto, BC Ramljak, D Anderson, LM DeGroff, V Stoner, GD Brueggemeier, RW Weghorst, CM AF Lynch, MA Petrel, TA Song, H Knobloch, TJ Casto, BC Ramljak, D Anderson, LM DeGroff, V Stoner, GD Brueggemeier, RW Weghorst, CM TI Responsiveness to transforming growth factor-beta (TGF-beta)-mediated growth inhibition is a function of membrane-bound TGF-beta type II receptor in human breast cancer cells SO GENE EXPRESSION LA English DT Article DE breast cancer; transforming growth factor-beta; transforming growth factor-beta receptors; growth inhibition ID MICROSATELLITE INSTABILITY; CARCINOMA CELLS; MCF-7 CELLS; EXPRESSION; GENE; MUTATION; COLON; RESISTANCE; TGF-BETA-1; LINES AB Transforming growth factor-beta (TGF-beta) is a potent inhibitor of growth and proliferation of breast epithelial cells, and loss of sensitivity to its effects has been associated with malignant transformation and tumorigenesis. The biological effects of TGF-beta are mediated by the TGF-beta receptor complex, a multimer composed of TGF-beta receptor type I (T betaR-I) and TGF-beta receptor type II (T betaR-II) subunits. Evidence suggests that loss of expression of TPR-II is implicated in the loss of sensitivity of tumorigenic breast cell lines to TGF-beta -mediated growth inhibition. A panel of human breast cell lines, including the immortalized MCF-10F and tumorigenic MCF-7, ZR75-1, BT474, T47-D, MDA-MB231, BT20, and SKBR-3 cell lines, was characterized for responsiveness to TGF-beta -induced G(1) growth arrest. Only the nontumorigenic MCF-10F and the tumorigenic MDA-MB231 cell lines demonstrated a significant inhibitory response to TGE-betaI and a significant binding of I-125-labeled TGF-beta ligand. While expression of T betaR-I mRNA was similar across the panel of cell lines, T betaR-II mRNA expression was decreased significantly in all seven tumorigenic cell lines in comparison with the nontumorigenic MCF-10F cell line. When total cellular protein was fractionated by centrifugation, T betaR-I protein was observed in both the cytosolic and membrane fractions at similar levels in all cell lines; however, T betaR-II protein was present in the cytosolic fraction in all cell lines, but was observed in the membrane fraction of only the TGF-beta -responsive MCF-10F and MDA-MB231 cells. Thus, lack of membrane-bound T betaR-II protein appears to be an important determinant of resistance to TGF-beta -mediated growth inhibition in this group of breast cell lines. C1 Ohio State Univ, Coll Med & Publ Hlth, Sch Publ Hlth,CHRI, Div Environm Hlth Sic, Columbus, OH 43210 USA. Ohio State Univ, Coll Pharm, Dept Med Chem & Pharmacognosy, Columbus, OH 43210 USA. NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Weghorst, CM (reprint author), Ohio State Univ, Coll Med & Publ Hlth, Sch Publ Hlth,CHRI, Div Environm Hlth Sic, Room 1148m,300 W 10th Ave, Columbus, OH 43210 USA. EM weghorst.2@osu.edu FU NCI NIH HHS [R21 CA66193, P30 CA016058, P30 CA16058]; NIDCR NIH HHS [1PO1 DE12704, P01 DE012704, R01 DE011943] NR 55 TC 14 Z9 15 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 1052-2166 J9 GENE EXPRESSION JI Gene Expr. PY 2001 VL 9 IS 4-5 BP 157 EP 171 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 449ED UT WOS:000169670600001 PM 11444526 ER PT J AU Sher, L AF Sher, L TI Possible genetic link between seasonal affective disorder and eating disorders SO GENERAL HOSPITAL PSYCHIATRY LA English DT Letter ID 5-HT2A PROMOTER POLYMORPHISM; ANOREXIA-NERVOSA; ASSOCIATION; SUSCEPTIBILITY C1 NIMH, Bethesda, MD 20892 USA. RP Sher, L (reprint author), NIMH, Bldg 10,Room 3S-231,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 12 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 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2001 VL 23 IS 1 BP 42 EP 43 DI 10.1016/S0163-8343(00)00119-5 PG 2 WC Psychiatry SC Psychiatry GA 405XB UT WOS:000167184900010 PM 11291638 ER PT J AU Karhu, R Ahlstedt-Soini, M Bittner, M Meltzer, P Trent, JM Isola, JJ AF Karhu, R Ahlstedt-Soini, M Bittner, M Meltzer, P Trent, JM Isola, JJ TI Chromosome arm-specific multicolor FISH SO GENES CHROMOSOMES & CANCER LA English DT Article ID HYBRIDIZATION AB Several systems for 24-color fluorescence in situ hybridization (FISH) have been developed and applied to karyotyping and detection of chromosomal abnormalities. We have developed a 42-color multicolor FISH (mFISH) technique (armFISH), which permits the detection of chromosomal aberrations at the resolution of chromosome arms. The armFISH uses a commercially available mFISH reagent kit (24XCyte, MetaSystems GmbH) supplemented with a set of differentially labeled chromosome arm-specific painting probes (arm-kit, comprising either p- or q-arms of all human chromosomes, except the p-arm of the acrocentric- and Y chromosomes). The mFISH-probe cocktail and the arm-kit are combined and hybridized together to metaphase chromosomes. The armFISH is analyzed in two steps; first, the conventional mFISH image analysis is performed, followed by the arm-kit analysis to reveal the chromosome arms involved. The examples demonstrate the utility of armFISH in defining chromosomal rearrangements of human cancers. (C) 2001 Wiley-Liss, Inc. C1 Tampere Univ Hosp, Canc Genet Lab, FIN-33521 Tampere, Finland. Univ Tampere, Canc Genet Lab, FIN-33101 Tampere, Finland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Karhu, R (reprint author), Tampere Univ Hosp, Canc Genet Lab, POB 2000, FIN-33521 Tampere, Finland. NR 9 TC 27 Z9 30 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JAN PY 2001 VL 30 IS 1 BP 105 EP 109 DI 10.1002/1098-2264(2000)9999:9999<::AID-GCC1068>3.0.CO;2-9 PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 379NE UT WOS:000165648300015 PM 11107184 ER PT J AU Elenbaas, B Spirio, L Koerner, F Fleming, MD Zimonjic, DB Donaher, JL Popescu, NC Hahn, WC Weinberg, RA AF Elenbaas, B Spirio, L Koerner, F Fleming, MD Zimonjic, DB Donaher, JL Popescu, NC Hahn, WC Weinberg, RA TI Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells SO GENES & DEVELOPMENT LA English DT Article DE transformation; mammary; epithelial; ras; c-myc; fibroblast ID HUMAN PAPILLOMAVIRUS TYPE-16; NUDE-MICE; TELOMERASE ACTIVITY; HUMAN FIBROBLASTS; GENE; PROGRESSION; EXPRESSION; RAS; GROWTH; P53 AB A number of genetic mutations have been identified in human breast cancers, yet the specific combinations of mutations required in concert to form breast carcinoma cells remain unknown. One approach to identifying the genetic and biochemical alterations required for this process involves the transformation of primary human mammary epithelial cells (HMECs) to carcinoma cells through the introduction of specific genes. Here we show that introduction of three genes encoding the SV40 large-T antigen, the telomerase catalytic subunit, and an H-Ras oncoprotein into primary HMECs results in cells that form tumors when transplanted subcutaneously or into the mammary glands of immunocompromised mice. The tumorigenicity of these transformed cells was dependent on the level of ras oncogene expression. Interestingly, transformation of HMECs but not two other human cell types was associated with amplifications of the c-myc oncogene, which occurred during the in vitro growth of the cells. Tumors derived from the transformed HMECs were poorly differentiated carcinomas that infiltrated through adjacent tissue. When these cells were injected subcutaneously, tumors formed in only half of the injections and with an average latency of 7.5 weeks. Mixing the epithelial tumor cells with Matrigel or primary human mammary fibroblasts substantially increased the efficiency of tumor formation and decreased the latency of tumor formation, demonstrating a significant influence of the stromal microenvironment on tumorigenicity. Thus, these observations establish an experimental system for elucidating both the genetic and cell biological requirements for the development of breast cancer. C1 MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Weinberg, RA (reprint author), MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. FU NCI NIH HHS [5 P01 CA80111-02, P01 CA080111] NR 51 TC 550 Z9 564 U1 2 U2 18 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 1 PY 2001 VL 15 IS 1 BP 50 EP 65 DI 10.1101/gad.828901 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 392MP UT WOS:000166415500007 PM 11156605 ER PT J AU Swaminathan, S Ellis, HM Waters, LS Yu, DG Lee, EC Court, DL Sharan, SK AF Swaminathan, S Ellis, HM Waters, LS Yu, DG Lee, EC Court, DL Sharan, SK TI Rapid engineering of bacterial artificial chromosomes using oligonucleotides SO GENESIS LA English DT Article DE BAC manipulation; phage recombination system; oligonucleotides ID ESCHERICHIA-COLI; DNA; RECOMBINATION; SEQUENCE; GENE AB A rapid method obviating the use of selectable markers to genetically manipulate large DNA inserts cloned into bacterial artificial chromosomes is described. Mutations such as single-base changes, deletions, and insertions can be recombined into a BAC by using synthetic single-stranded oligonucleotides as targeting vectors, The oligonucleotides include the mutated sequence flanked by short homology arms of 35-70 bases on either side that recombine with the BAG. In the absence of any selectable marker, modified BACs are identified by specific PCR amplification of the mutated BAC from cultures of pooled bacterial cells. Each pool represents about 10 electroporated cells from the original recombination mixture. Subsequently, individual clones containing the desired alteration are identified from the positive pools. Using this BAC modification method, we have observed a frequency of one recombinant clone per 90-260 electroporated cells. The combination of high targeting frequency and the sensitive yet selective PCR-based screening method makes BAC manipulation using oligonucleotides both rapid and simple. genesis 29:14-21, 2001. Published 2001 Wiley-Liss, Inc.(dagger). C1 NCI, Genet Canc Susceptibil Grp, Mouse Canc Genet Program, Frederick, MD 21702 USA. NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Sharan, SK (reprint author), NCI, Genet Canc Susceptibil Grp, Mouse Canc Genet Program, POB B,Bldg 538,Room 133, Frederick, MD 21702 USA. NR 11 TC 101 Z9 108 U1 1 U2 12 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1526-954X J9 GENESIS JI Genesis PD JAN PY 2001 VL 29 IS 1 BP 14 EP 21 DI 10.1002/1526-968X(200101)29:1<14::AID-GENE1001>3.0.CO;2-X PG 8 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 396ZK UT WOS:000166668100002 PM 11135458 ER PT S AU Chandrasekharappa, SC Teh, BT AF Chandrasekharappa, SC Teh, BT BE Dahia, PLM Eng, C TI Clinical and molecular aspects of multiple endocrine neoplasia type 1 SO GENETIC DISORDERS OF ENDOCRINE NEOPLASIA SE Frontiers of Hormone Research LA English DT Review ID TUMOR-SUPPRESSOR GENE; FAMILIAL ISOLATED HYPERPARATHYROIDISM; ZOLLINGER-ELLISON SYNDROME; FIBROBLAST GROWTH-FACTOR; MEN1 GENE; PARATHYROID TUMORS; MUTATION ANALYSIS; PITUITARY-TUMORS; SPORADIC GASTRINOMAS; TRANSCRIPTION FACTOR C1 NHGRI, Genet & Mol BIol Branch, NIH, Bethesda, MD 20892 USA. Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA. RP NHGRI, Genet & Mol BIol Branch, NIH, Bethesda, MD 20892 USA. EM chandra@nhgri.nih.gov; bin.teh@vai.org NR 120 TC 2 Z9 2 U1 1 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-3073 BN 3-8055-7203-4 J9 FRONT HORM RES JI Front.Horm.Res. PY 2001 VL 28 BP 50 EP 80 PG 31 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BS89B UT WOS:000171319400005 PM 11443853 ER PT J AU Marsh, DJ Stratakis, CA AF Marsh, DJ Stratakis, CA TI Hamartoma and lentiginosis syndromes: Clinical and molecular aspects SO GENETIC DISORDERS OF ENDOCRINE NEOPLASIA SE FRONTIERS OF HORMONE RESEARCH LA English DT Review ID PEUTZ-JEGHERS-SYNDROME; TUMOR-SUPPRESSOR GENE; RILEY-RUVALCABA-SYNDROME; FAMILIAL JUVENILE POLYPOSIS; LHERMITTE-DUCLOS-DISEASE; SPOTTY SKIN PIGMENTATION; BANNAYAN-ZONANA-SYNDROME; SCHWANNOMAS CARNEY-COMPLEX; NODULAR ADRENOCORTICAL DISEASE; GERMLINE PTEN MUTATION C1 Royal N Shore Hosp, Kolling Inst Med Res, St Leonards, NSW 2065, Australia. Univ Sydney, Sydney, NSW 2006, Australia. NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Marsh, DJ (reprint author), Royal N Shore Hosp, Kolling Inst Med Res, St Leonards, NSW 2065, Australia. RI Marsh, Deborah/I-1491-2014 OI Marsh, Deborah/0000-0001-5899-4931 NR 262 TC 3 Z9 4 U1 2 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-3073 J9 FRONT HORM RES JI Front.Horm.Res. PY 2001 VL 28 BP 167 EP 213 PG 47 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BS89B UT WOS:000171319400009 PM 11443851 ER PT J AU Bai, Y Goldin, LR Goldstein, AM AF Bai, Y Goldin, LR Goldstein, AM TI Gene x environment interaction from case-control and case-case approaches SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 12 (GAW12) CY OCT 23-26, 2000 CL SAN ANTONIO, TEXAS DE case-case; case-control; gene x environment interaction ID CASE-ONLY DESIGNS AB Using the Genetic Analysis Workshop 12 data, we applied case-control and case-case approaches to study the effects of a major gene and its interaction with sex on the disease liability. Although no joint additive effect was simulated, the case-case approach detected a small but significant multiplicative interaction effect, which could not be explained by the effect of random error. Given that analyses of "real" data will not be made with the knowledge of the true effects a priori, this study showed that the measure of gene x environment interaction is critical and the definition of interaction should be explicit. (C) 2001 Wiley-Liss, Inc. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Bai, Y (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA. NR 10 TC 2 Z9 2 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2001 VL 21 SU 1 BP S825 EP S830 PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 480LK UT WOS:000171462700153 PM 11793787 ER PT J AU Bailey-Wilson, JE Sorant, AJM Malley, JD Presciuttini, S Redner, RA Severini, TA Badner, JA Pajevic, S Jufer, R Baffoe-Bonnie, A Kao, L Doan, BQ Goldstein, JL Holmes, TN Behneman, D Mandal, DM Turley, TN Weissbecker, KA O'Neill, J Pugh, EW AF Bailey-Wilson, JE Sorant, AJM Malley, JD Presciuttini, S Redner, RA Severini, TA Badner, JA Pajevic, S Jufer, R Baffoe-Bonnie, A Kao, L Doan, BQ Goldstein, JL Holmes, TN Behneman, D Mandal, DM Turley, TN Weissbecker, KA O'Neill, J Pugh, EW TI Comparison of novel and existing methods for detection of linkage disequilibrium using parent-child trios in the GAW12 genetic isolate simulated data SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 12 (GAW12) CY OCT 23-26, 2000 CL SAN ANTONIO, TEXAS DE association; ELAAT; linkage disequilibrium; power; TDT ID TRANSMISSION/DISEQUILIBRIUM TEST; ASSOCIATION; TDT AB A novel method for joint detection of association caused by linkage disequilibrium (LD) and estimation of both recombination fraction and linkage disequilibrium parameters was compared to several existing implementations of the transmission/disequilibrium test (TDT) and modifications of the TDT in the simulated genetic isolate data from Genetic Analysis Workshop 12. The first completely genotyped trio of affected child and parents was selected from each family in each replicate so that the TDT tests are valid tests of linkage and association, rather than being only valid as tests for linkage. In general, power to detect LD using the genome-wide scan markers was inadequate in the individual replicate samples, but the power was better when analyzing several SNP markers in candidate gene 1. ((C)) 2001 Wiley-Liss, Inc. C1 NIH, Ctr Informat Technol, Baltimore, MD 21224 USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. Johns Hopkins Sch Med, Ctr Inherited Dis Res, Baltimore, MD USA. Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Northwestern Univ, Dept Stat, Evanston, IL 60208 USA. Univ Tulsa, Dept Math & Comp Sci, Tulsa, OK 74104 USA. Univ Pisa, Dept Biomed, Pisa, Italy. NHGRI, NIH, Baltimore, MD 21224 USA. RP Bailey-Wilson, JE (reprint author), NHGRI, NIH, 333 Cassell Dr,Suite 2000, Baltimore, MD 21224 USA. FU NCRR NIH HHS [RR03655] NR 11 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2001 VL 21 SU 1 BP S378 EP S383 PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 480LK UT WOS:000171462700071 PM 11793703 ER PT J AU Bailey-Wilson, JE AF Bailey-Wilson, JE TI Introduction: Association and transmission/disequilibrium test analyses of discrete traits in the GAW12 simulated data SO GENETIC EPIDEMIOLOGY LA English DT Editorial Material C1 NHGRI, NIH, Baltimore, MD 21224 USA. RP Bailey-Wilson, JE (reprint author), NHGRI, NIH, 333 Cassell Dr,Suite 2000, Baltimore, MD 21224 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2001 VL 21 SU 1 BP S376 EP S377 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 480LK UT WOS:000171462700070 PM 11793702 ER PT J AU Goldin, LR AF Goldin, LR TI Introduction: Linkage analysis of quantitative traits SO GENETIC EPIDEMIOLOGY LA English DT Editorial Material C1 NCI, Genet Epidemiol Branch, DCEG, Bethesda, MD 20892 USA. RP Goldin, LR (reprint author), NCI, Genet Epidemiol Branch, DCEG, 6120 Execut Blvd,Rm 7008,MSC 7236, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2001 VL 21 SU 1 BP S459 EP S460 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 480LK UT WOS:000171462700085 PM 11858135 ER PT J AU Hardy, SW Weir, BS Kaplan, NL Martin, ER AF Hardy, SW Weir, BS Kaplan, NL Martin, ER TI Analysis of single nucleotide polymorphisms in candidate genes using the pedigree disequilibrium test SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 12 (GAW12) CY OCT 23-26, 2000 CL SAN ANTONIO, TEXAS DE association; linkage disequilibrium; pedigree disequilibrium test; SNPs ID SIBSHIP TEST; LINKAGE; ASSOCIATION AB The pedigree disequilibrium test (PDT) has been proposed recently as a test for association in general pedigrees [Martin et al., Am J Hum Genet 67:146-54, 2000]. The Genetic Analysis Workshop (GAW) 12 simulated data, with many extended pedigrees, is an example the type of data to which the PDT is ideally suited. In replicate 42 from the general population the PDT correctly identifies candidate genes 1, 2, and 6 as containing single nucleotide polymorphisms (SNPs) that are significantly associated with the disease. We also applied the truncated product method (TPM) [Zaykin et al., Genet Epidemiol, in press] to combine p-values in overlapping windows across the genes. Our results show that the TPM is helpful in identifying significant SII Ps as well as removing spurious false positives. Our results indicate that, using the PDT, functional disease-associated SNPs can be successfully identified with a dense map of moderately polymorphic SNPs. ((C)) 2001 Wiley-Liss, Inc. C1 Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC 27710 USA. N Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27695 USA. Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA. RP Martin, ER (reprint author), Duke Univ, Med Ctr, Ctr Human Genet, Box 3468, Durham, NC 27710 USA. FU NIGMS NIH HHS [GM45344]; NIMH NIH HHS [R01 MH-59528]; NINDS NIH HHS [2P50 NS-39764-02] NR 6 TC 3 Z9 3 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2001 VL 21 SU 1 BP S441 EP S446 PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 480LK UT WOS:000171462700082 PM 11793716 ER PT J AU Martinez, M Goldstein, AM O'Connell, JR AF Martinez, M Goldstein, AM O'Connell, JR TI Comparison of likelihood approaches for combined segregation and linkage analysis of a complex disease and a candidate gene marker under different ascertainment schemes SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 12 (GAW12) CY OCT 23-26, 2000 CL SAN ANTONIO, TEXAS DE ascertainment; genexcovariate interactions; linkage disequilibrium; segregation and linkage analysis ID REGRESSIVE LOGISTIC-MODELS; FAMILIAL DISEASES AB We compared two joint likelihood approaches, with complete (LI) or without (L2) linkage disequilibrium, under different ascertainment schemes, for the genetic analysis of the disease trait and marker gene I in replicate 42. Joint likelihoods were computed without a correction for the selection scheme. For the different sam ling schemes we have explored, our results suggest that L1 is a more powerful approach than L2 to detect major gene and covariate effects as well as to identify accurately genexcovariate interaction effects in a common and complex disease such as the Genetic Analysis Workshop 12 MG6 simulated trait. (C) 2001Wiley-Liss, Inc. C1 INSERM, EMI 00 06, Paris, France. NCI, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Martinez, M (reprint author), Hop St Louis, INSERM, EPI 00 06, 1 Ave Claude Vellefaux, F-75010 Paris, France. RI Martinez, Maria/B-3111-2013 OI Martinez, Maria/0000-0003-2180-4537 NR 12 TC 1 Z9 1 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2001 VL 21 SU 1 BP S760 EP S765 PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 480LK UT WOS:000171462700140 PM 11793774 ER PT J AU Pugh, EW Papanicolaou, GJ Justice, CM Roy-Gagnon, MH Sorant, AJM Kingman, A Wilson, AF AF Pugh, EW Papanicolaou, GJ Justice, CM Roy-Gagnon, MH Sorant, AJM Kingman, A Wilson, AF TI Comparison of variance components, ANOVA and regression of offspring on midparent (ROMP) methods for SNP markers SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 12 (GAW12) CY OCT 23-26, 2000 CL SAN ANTONIO, TEXAS DE analysis of variance; candidate locus; heritability; regression of offspring on midparent; variance components ID PEDIGREES; LINKAGE AB An extension of the traditional regression of offspring on midparent (ROMP) method was used to estimate the heritability of the trait, test for marker association, and estimate the heritability attributable to a marker locus. The fifty replicates of the Genetic Analysis Workshop (GAW) 12 simulated general population data were used to compare the ROMP method with the variance components method as implemented in SOLAR as a test for marker association, and to a standard analysis of variance (ANOVA) method. Large sample statistical properties of the ROMP and ANOVA methods were compared using 2,000 replicates resampled from the families of the original 50 replicates. Overall, the power to detect a completely associated single nucleotide polymorphism (SNP) marker was high, and the type I error rates were similar to nominal significance levels for all three methods. The standard deviations of the estimates of the heritability of the trait were large for both SOLAR and ROMP, but the estimates were, on average, close to those of the generating model for both methods. However, on average, SOLAR overestimated the heritability attributable to the associated SNP marker (by 256%) while ROMP underestimated it (by 26%). (C) 2001 Wiley-Liss, Inc. C1 NHGRI, Genometr Sect, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD 21218 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Wilson, AF (reprint author), NHGRI, Genometr Sect, NIH, 333 Cassell Dr,Suite 2000, Baltimore, MD 21224 USA. RI Wilson, Alexander/C-2320-2009 NR 6 TC 6 Z9 6 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2001 VL 21 SU 1 BP S794 EP S799 PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 480LK UT WOS:000171462700147 PM 11793780 ER PT J AU Yang, XH Goldstein, AM Chase, GA Gastwirth, JL Goldin, LR AF Yang, XH Goldstein, AM Chase, GA Gastwirth, JL Goldin, LR TI Use of weighted p-values in regional inference procedures SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 12 (GAW12) CY OCT 23-26, 2000 CL SAN ANTONIO, TEXAS DE linkage; multipoint analysis; power; quantitative trait; regional linkage methods ID TRAIT LINKAGE ANALYSIS; PEDIGREES; GENES AB Our previous studies have demonstrated that the power to detect linkage was improved by calculating a moving average of consecutive p-values in a small region as compared with testing all single p-valucs. The goal of this study was to test whether the power can be improved further with an alternative method whereby the middle p-values in the sequence were given more weight than the others. We also wanted to compare the moving average tests with multipoint linkage tests. The simulated extended pedigree data from the general population was analyzed to identify two major genes (MG1 and MG5) underlying two quantitative traits (Q1 and Q5). We used the variance components method implemented in the GENEHUNTER program to test for linkage of 14-marker regions each on chromosome 19 and chromosome 1 to the adjusted quantitative traits Q1 and Q5, respectively, in all 50 replicates. As before, we found that the moving average test was more powerful than a test based on single p-values. In some cases, the weighting procedure increased the power further and was similar to that of multipoint analysis, but this was not consistently found. In addition, all methods had low power and it is not possible to make a general conclusion that some weighting schemes are better than others. ((C)) 2001 Wiley-Liss, Inc. C1 NCI, Genet Epidemiol Branch, DCEG, NIH, Rockville, MD 20852 USA. Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, Detroit, MI USA. George Washington Univ, Dept Biostat, Washington, DC 20052 USA. RP Yang, XH (reprint author), NCI, Genet Epidemiol Branch, DCEG, NIH, Bldg EPS,Room 7005,6120 Execut Blvd, Rockville, MD 20852 USA. NR 9 TC 1 Z9 1 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2001 VL 21 SU 1 BP S484 EP S489 PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 480LK UT WOS:000171462700090 PM 11793723 ER PT J AU Li, ZH Gastwirth, JL AF Li, ZH Gastwirth, JL TI A weighted test using both extreme discordant and concordant sib pairs for detecting linkage SO GENETIC EPIDEMIOLOGY LA English DT Article DE linkage analysis; quantitative trait locus; weighted tests ID QUANTITATIVE-TRAIT LOCI; HUMANS AB Statistical procedures using extremely discordant and concordant sib-pairs have been developed for mapping quantitative trail loci in humans. To improve the power of the existing methods, test statistics placing greater weight on the more discordant or more concordant pairs are proposed. Because the optimum choice of weights would depend on the underlying genetic model, which is not usually known, a test with simple weights is suggested. This test is shown to have greater power than the currently available ones for a variety of genetic models. Genet. Epidemiol. 20:34-43, 2001. (C) 2001 Wiley-Liss, Inc. C1 George Washington Univ, Ctr Biostat, Dept Stat, Rockville, MD 20852 USA. George Washington Univ, Dept Stat, Washington, DC 20052 USA. NCI, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD USA. RP Li, ZH (reprint author), George Washington Univ, Ctr Biostat, Dept Stat, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. FU NCI NIH HHS [CA64363] NR 18 TC 3 Z9 3 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JAN PY 2001 VL 20 IS 1 BP 34 EP 43 DI 10.1002/1098-2272(200101)20:1<34::AID-GEPI4>3.3.CO;2-B PG 10 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 385BX UT WOS:000165982700004 PM 11119295 ER PT J AU Aravind, L Koonin, EV AF Aravind, L. Koonin, Eugene V. TI The DNA-repair protein AlkB, EGL-9, and leprecan define new families of 2-oxoglutarate- and iron-dependent dioxygenases SO GENOME BIOLOGY LA English DT Article AB Background: Protein fold recognition using sequence profile searches frequently allows prediction of the structure and biochemical mechanisms of proteins with an important biological function but unknown biochemical activity. Here we describe such predictions resulting from an analysis of the 2-oxoglutarate ( 2OG) and Fe( II)-dependent oxygenases, a class of enzymes that are widespread in eukaryotes and bacteria and catalyze a variety of reactions typically involving the oxidation of an organic substrate using a dioxygen molecule. Results: We employ sequence profile analysis to show that the DNA repair protein AlkB, the extracellular matrix protein leprecan, the disease-resistance-related protein EGL-9 and several uncharacterized proteins define novel families of enzymes of the 2OG-Fe( II) oxygenase superfamily. The identification of AlkB as a member of the 2OG-Fe( II) oxygenase superfamily suggests that this protein catalyzes oxidative detoxification of alkylated bases. More distant homologs of AlkB were detected in eukaryotes and in plant RNA viruses, leading to the hypothesis that these proteins might be involved in RNA demethylation. The EGL-9 protein from Caenorhabditis elegans is necessary for normal muscle function and its inactivation results in resistance against paralysis induced by the Pseudomonas aeruginosa toxin. EGL-9 and leprecan are predicted to be novel protein hydroxylases that might be involved in the generation of substrates for protein glycosylation. Conclusions: Here, using sequence profile searches, we show that several previously undetected protein families contain 2OG-Fe( II) oxygenase fold. This allows us to predict the catalytic activity for a wide range of biologically important, but biochemically uncharacterized proteins from eukaryotes and bacteria. C1 [Aravind, L.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM aravind@ncbi.nlm.nih.gov NR 33 TC 29 Z9 31 U1 5 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2001 VL 2 IS 3 AR 0007.1 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V12EY UT WOS:000207583700011 ER PT J AU Iyer, LM Aravind, L Bork, P Hofmann, K Mushegian, AR Zhulin, IB Koonin, EV AF Iyer, Lakshminarayan M. Aravind, L. Bork, Peer Hofmann, Kay Mushegian, Arcady R. Zhulin, Igor B. Koonin, Eugene V. TI Quod erat demonstrandum? The mystery of experimental validation of apparently erroneous computational analyses of protein sequences SO GENOME BIOLOGY LA English DT Article AB Background: Computational predictions are critical for directing the experimental study of protein functions. Therefore it is paradoxical when an apparently erroneous computational prediction seems to be supported by experiment. Results: We analyzed six cases where application of novel or conventional computational methods for protein sequence and structure analysis led to non-trivial predictions that were subsequently supported by direct experiments. We show that, on all six occasions, the original prediction was unjustified, and in at least three cases, an alternative, well-supported computational prediction, incompatible with the original one, could be derived. The most unusual cases involved the identification of an archaeal cysteinyl-tRNA synthetase, a dihydropteroate synthase and a thymidylate synthase, for which experimental verifications of apparently erroneous computational predictions were reported. Using sequence-profile analysis, multiple alignment and secondary-structure prediction, we have identified the unique archaeal 'cysteinyl-tRNA synthetase' as a homolog of extracellular polygalactosaminidases, and the 'dihydropteroate synthase' as a member of the beta-lactamase-like superfamily of metal-dependent hydrolases. Conclusions: In each of the analyzed cases, the original computational predictions could be refuted and, in some instances, alternative strongly supported predictions were obtained. The nature of the experimental evidence that appears to support these predictions remains an open question. Some of these experiments might signify discovery of extremely unusual forms of the respective enzymes, whereas the results of others could be due to artifacts. C1 [Iyer, Lakshminarayan M.; Aravind, L.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Bork, Peer] EMBL, D-69117 Heidelberg, Germany. [Hofmann, Kay] MEMOREC Stoffel GmbH, D-50829 Cologne, Germany. [Zhulin, Igor B.] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. [Mushegian, Arcady R.] Stowers Inst Med Res, Kansas City, MO 64410 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Zhulin, Igor/A-2308-2012; Bork, Peer/F-1813-2013 OI Zhulin, Igor/0000-0002-6708-5323; Bork, Peer/0000-0002-2627-833X NR 62 TC 43 Z9 43 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2001 VL 2 IS 12 AR 0051.1 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V12FI UT WOS:000207584700007 ER PT J AU Jordan, IK Kondrashov, FA Rogozin, IB Tatusov, RL Wolf, YI Koonin, EV AF Jordan, I. King Kondrashov, Fyodor A. Rogozin, Igor B. Tatusov, Roman L. Wolf, Yuri I. Koonin, Eugene V. TI Constant relative rate of protein evolution and detection of functional diversification among bacterial, archaeal and eukaryotic proteins SO GENOME BIOLOGY LA English DT Article AB Background: Detection of changes in a protein's evolutionary rate may reveal cases of change in that protein's function. We developed and implemented a simple relative rates test in an attempt to assess the rate constancy of protein evolution and to detect cases of functional diversification between orthologous proteins. The test was performed on clusters of orthologous protein sequences from complete bacterial genomes (Chlamydia trachomatis, C. muridarum and Chlamydophila pneumoniae), complete archaeal genomes (Pyrococcus horikoshii, P. abyssi and P. furiosus) and partially sequenced mammalian genomes (human, mouse and rat). Results: Amino-acid sequence evolution rates are significantly correlated on different branches of phylogenetic trees representing the great majority of analyzed orthologous protein sets from all three domains of life. However, approximately 1% of the proteins from each group of species deviates from this pattern and instead shows variation that is consistent with an acceleration of the rate of amino-acid substitution, which may be due to functional diversification. Most of the putative functionally diversified proteins from all three species groups are predicted to function at the periphery of the cells and mediate their interaction with the environment. Conclusions: Relative rates of protein evolution are remarkably constant for the three species groups analyzed here. Deviations from this rate constancy are probably due to changes in selective constraints associated with diversification between orthologs. Functional diversification between orthologs is thought to be a relatively rare event. However, the resolution afforded by the test designed specifically for genomic-scale datasets allowed us to identify numerous cases of possible functional diversification between orthologous proteins. C1 [Jordan, I. King; Kondrashov, Fyodor A.; Rogozin, Igor B.; Tatusov, Roman L.; Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Jordan, IK (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM Jordan@ncbi.nlm.nih.gov RI Kondrashov, Fyodor Alexeevich/H-6331-2015 OI Kondrashov, Fyodor Alexeevich/0000-0001-8243-4694 NR 36 TC 4 Z9 4 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2001 VL 2 IS 12 AR 0053.1 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V12FI UT WOS:000207584700011 ER PT J AU Koonin, EV AF Koonin, Eugene V. TI An apology for orthologs - or brave new memes SO GENOME BIOLOGY LA English DT Editorial Material C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@nebi.nlm.nih.gov NR 3 TC 3 Z9 4 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2001 VL 2 IS 4 AR 1005.1 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V12EZ UT WOS:000207583800002 ER PT J AU Lam, LT Pickeral, OK Peng, AC Rosenwald, A Hurt, EM Giltnane, JM Averett, LM Zhao, H Davis, RE Sathyamoorthy, M Wahl, LM Harris, ED Mikovits, JA Monks, AP Hollingshead, MG Sausville, EA Staudt, LM AF Lam, Lloyd T. Pickeral, Oxana K. Peng, Amy C. Rosenwald, Andreas Hurt, Elaine M. Giltnane, Jena M. Averett, Lauren M. Zhao, Hong Davis, R. Eric Sathyamoorthy, Mohan Wahl, Larry M. Harris, Eric D. Mikovits, Judy A. Monks, Anne P. Hollingshead, Melinda G. Sausville, Edward A. Staudt, Louis M. TI Genomic-scale measurement of mRNA turnover and the mechanisms of action of the anti-cancer drug flavopiridol SO GENOME BIOLOGY LA English DT Article AB Background: Flavopiridol, a flavonoid currently in cancer clinical trials, inhibits cyclin-dependent kinases (CDKs) by competitively blocking their ATP-binding pocket. However, the mechanism of action of flavopiridol as an anti-cancer agent has not been fully elucidated. Results: Using DNA microarrays, we found that flavopiridol inhibited gene expression broadly, in contrast to two other CDK inhibitors, roscovitine and 9-nitropaullone. The gene expression profile of flavopiridol closely resembled the profiles of two transcription inhibitors, actinomycin D and 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole (DRB), suggesting that flavopiridol inhibits transcription globally. We were therefore able to use flavopiridol to measure mRNA turnover rates comprehensively and we found that different functional classes of genes had distinct distributions of mRNA turnover rates. In particular, genes encoding apoptosis regulators frequently had very short half-lives, as did several genes encoding key cell-cycle regulators. Strikingly, genes that were transcriptionally inducible were disproportionately represented in the class of genes with rapid mRNA turnover. Conclusions: The present genomic-scale measurement of mRNA turnover uncovered a regulatory logic that links gene function with mRNA half-life. The observation that transcriptionally inducible genes often have short mRNA half-lives demonstrates that cells have a coordinated strategy to rapidly modulate the mRNA levels of these genes. In addition, the present results suggest that flavopiridol may be more effective against types of cancer that are highly dependent on genes with unstable mRNAs. C1 [Lam, Lloyd T.; Pickeral, Oxana K.; Rosenwald, Andreas; Hurt, Elaine M.; Giltnane, Jena M.; Averett, Lauren M.; Zhao, Hong; Davis, R. Eric; Sathyamoorthy, Mohan; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Peng, Amy C.] EMMES Corp, Rockville, MD 20850 USA. [Wahl, Larry M.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. [Harris, Eric D.; Mikovits, Judy A.; Monks, Anne P.; Hollingshead, Melinda G.; Sausville, Edward A.] NCI, Dev Therapeut Program, DTP Clin Trials Unit, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM lstaudt@box-l.nih.gov RI Giltnane, Jennifer/D-2584-2013 NR 42 TC 50 Z9 50 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2001 VL 2 IS 10 AR 0041.1 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V12FG UT WOS:000207584500006 ER PT J AU Makarova, KS Ponomarev, VA Koonin, EV AF Makarova, Kira S. Ponomarev, Vladimir A. Koonin, Eugene V. TI Two C or not two C: recurrent disruption of Zn-ribbons, gene duplication, lineage-specific gene loss, and horizontal gene transfer in evolution of bacterial ribosomal proteins SO GENOME BIOLOGY LA English DT Article AB Background: Ribosomal proteins are encoded in all genomes of cellular life forms and are, generally, well conserved during evolution. In prokaryotes, the genes for most ribosomal proteins are clustered in several highly conserved operons, which ensures efficient co-regulation of their expression. Duplications of ribosomal-protein genes are infrequent, and given their coordinated expression and functioning, it is generally assumed that ribosomal-protein genes are unlikely to undergo horizontal transfer. However, with the accumulation of numerous complete genome sequences of prokaryotes, several paralogous pairs of ribosomal protein genes have been identified. Here we analyze all such cases and attempt to reconstruct the evolutionary history of these ribosomal proteins. Results: Complete bacterial genomes were searched for duplications of ribosomal proteins. Ribosomal proteins L36, L33, L31, S14 are each duplicated in several bacterial genomes and ribosomal proteins L11, L28, L7/L12, S1, S15, S18 are so far duplicated in only one genome each. Sequence analysis of the four ribosomal proteins, for which paralogs were detected in several genomes, two of the ribosomal proteins duplicated in one genome (L28 and S18), and the ribosomal protein L32 showed that each of them comes in two distinct versions. One form contains a predicted metal-binding Zn-ribbon that consists of four conserved cysteines (in some cases replaced by histidines), whereas, in the second form, these metal-chelating residues are completely or partially replaced. Typically, genomes containing paralogous genes for these ribosomal proteins encode both versions, designated C+ and C-, respectively. Analysis of phylogenetic trees for these seven ribosomal proteins, combined with comparison of genomic contexts for the respective genes, indicates that in most, if not all cases, their evolution involved a duplication of the ancestral C+ form early in bacterial evolution, with subsequent alternative loss of the C+ and C- forms in different lineages. Additionally, evidence was obtained for a role of horizontal gene transfer in the evolution of these ribosomal proteins, with multiple cases of gene displacement 'in situ', that is, without a change of the gene order in the recipient genome. Conclusions: A more complex picture of evolution of bacterial ribosomal proteins than previously suspected is emerging from these results, with major contributions of lineage-specific gene loss and horizontal gene transfer. The recurrent theme of emergence and disruption of Zn-ribbons in bacterial ribosomal proteins awaits a functional interpretation. C1 [Makarova, Kira S.; Ponomarev, Vladimir A.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Makarova, Kira S.] Uniformed Serv Univ Hlth Sci, Dept Pathol, FE Hebert Sch Med, Bethesda, MD 20814 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov FU Office of Biological and Environmental Research, DOE [DE-FG02-98ER62583] FX We thank Yuri I. Wolf for help and advice with phylogenetic tree construction, and I. King Jordan for critical reading of the manuscript. Kira Makarova is supported by the Microbial Genome Program, Office of Biological and Environmental Research, DOE (DE-FG02-98ER62583). NR 42 TC 3 Z9 3 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2001 VL 2 IS 9 AR 0033.1 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V12FF UT WOS:000207584400012 ER PT J AU Makarova, KS Mironov, AA Gelfand, MS AF Makarova, Kira S. Mironov, Andrey A. Gelfand, Mikhail S. TI Conservation of the binding site for the arginine repressor in all bacterial lineages SO GENOME BIOLOGY LA English DT Article AB Background: The arginine repressor ArgR/AhrC is a transcription factor universally conserved in bacterial genomes. Its recognition signal (the ARG box), a weak palindrome, is also conserved between genomes, despite a very low degree of similarity between individual sites within a genome. Thus, the arginine repressor is different from two other universal transcription factors HrcA, whose recognition signal is very strongly conserved both within and between genomes, and LexA/DinR, whose signal is strongly conserved within, but not between, genomes. The arginine regulon is well studied in Escherichia coli and to some extent in Bacillus subtilis and some other genomes. Here, we apply the comparative genomic approach to the prediction of the ArgR-binding sites in all completely sequenced bacterial genomes. Results: Orthologs of ArgR/AhrC were identified in the complete genomes of E. coli, Haemophilus influenzae, Vibrio cholerae, B. subtilis, Mycobacterium tuberculosis, Thermotoga maritima, Chlamydia pneumoniae and Deinococcus radiodurans. Candidate arginine repressor binding sites were identified upstream of arginine transport and metabolism genes. Conclusions: We found that the ArgR/AhrC recognition signal is conserved in all genomes that contain genes encoding orthologous transcription factors of this family. All genomes studied except M. tuberculosis contain ABC transport cassettes (related to the Art system of E. coli) belonging to the candidate arginine regulons. C1 [Mironov, Andrey A.; Gelfand, Mikhail S.] State Sci Ctr GosNIIGenetika, Moscow 113545, Russia. [Makarova, Kira S.] Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. [Makarova, Kira S.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Makarova, Kira S.] Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. RP Gelfand, MS (reprint author), State Sci Ctr GosNIIGenetika, Moscow 113545, Russia. EM misha@imb.imb.ac.ru RI Mironov, Andrey/C-8024-2012; Gelfand, Mikhail/F-3425-2012 FU Merck Genome Research Institute [244]; Russian Fund of Basic Research [9904-48247, 00-15-99362]; Russian State Scientific Program 'Human Genome', INTAS [99-1476]; Howard Hughes Medical Institute [55000309]; Office of Biological and Environmental Research, DOE [DE-FG02-98ER62583] FX We thank Eugene Koonin, Yury Kozlov and Igor Rogosin for useful discussions. This study was partially supported by grants from the Merck Genome Research Institute (244), the Russian Fund of Basic Research (9904-48247 and 00-15-99362), the Russian State Scientific Program 'Human Genome', INTAS (99-1476), the Howard Hughes Medical Institute (55000309), and Microbial Genome Program, Office of Biological and Environmental Research, DOE (DE-FG02-98ER62583). NR 42 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2001 VL 2 IS 4 AR 0013.1 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V12EZ UT WOS:000207583800009 ER PT J AU Murphy, WJ Stanyon, R O'Brien, SJ AF Murphy, William J. Stanyon, Roscoe O'Brien, Stephen J. TI Evolution of mammalian genome organization inferred from comparative gene mapping SO GENOME BIOLOGY LA English DT Review AB Comparative genome analyses, including chromosome painting in over 40 diverse mammalian species, ordered gene maps from several representatives of different mammalian and vertebrate orders, and large-scale sequencing of the human and mouse genomes are beginning to provide insight into the rates and patterns of chromosomal evolution on a whole-genome scale, as well as into the forces that have sculpted the genomes of extant mammalian species. C1 [Murphy, William J.; Stanyon, Roscoe; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Murphy, WJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. EM murphywi@mail.nciferf.gov NR 68 TC 1 Z9 1 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2001 VL 2 IS 6 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V12FC UT WOS:000207584100003 ER PT J AU Stenger, JE Lobachev, KS Gordenin, D Darden, TA Jurka, J Resnick, MA AF Stenger, JE Lobachev, KS Gordenin, D Darden, TA Jurka, J Resnick, MA TI Biased distribution of inverted and direct Alus in the human genome: Implications for insertion, exclusion, and genome stability SO GENOME RESEARCH LA English DT Article ID EHLERS-DANLOS-SYNDROME; LYSYL HYDROXYLASE GENE; SACCHAROMYCES-CEREVISIAE; REPETITIVE SEQUENCE; DNA REPEATS; VI VARIANT; 7 EXONS; RECOMBINATION; DELETION; INSTABILITY AB Alu sequences, the most abundant class of large dispersed DNA repeats in human chromosomes, contribute to human genome dynamics. Recently we reported that long inverted repeats, including human Alus, can be strong initiators of genetic change in yeast. We proposed that the potential For interactions between adjacent, closely related Alus would influence their stability and this would be reflected in their distribution. We have undertaken an extensive computational analysis of all Alus [the database is at http://dir.niehs.nih.gov/ALU) to better understand their distribution and circumstances under which Alu sequences might affect genome stability. Alus separated by <650 bp were categorized according to orientation, length of regions sharing high sequence identity, distance between highly identical regions, and extent of sequence identity. Nearly 50% of all Alu pairs have long alignable regions (>275 bp), corresponding to nearly Full-length Alus, regardless of orientation. There are dramatic differences in the distributions and character of Alu pairs with closely spaced, nearly identical regions. For Alu pairs that are directly repetitive, similar to 30% have highly identical regions separated by <20 bp, but only when the alignments correspond to near full-size or half-size Alus. The opposite is found for the distribution of inverted repeats: Ala pairs with aligned regions separated by <20 bp are rare. Furthermore, closely spaced direct and inverted Alus differ in their truncation patterns, suggesting differences in the mechanisms of insertion. At larger distances, the direct and inverted Alo pairs have similar distributions. We propose that sequence identity, orientation, and distance are important Factors determining insertion of adjacent Alus, the frequency and spectrum of Alu-associated changes in the genome, and the contribution of Alu pairs to genome instability. Based on results in model systems and the present analysis, closely spaced inverted Alu pairs with long regions of alignment are likely at-risk motifs (ARMs] for genome instability. C1 NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. Genet Informat Res Inst, Sunnyvale, CA 94089 USA. RP Resnick, MA (reprint author), NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. OI Gordenin, Dmitry/0000-0002-8399-1836 NR 57 TC 87 Z9 87 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JAN PY 2001 VL 11 IS 1 BP 12 EP 27 DI 10.1101/gr.158801 PG 16 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 391NH UT WOS:000166361700003 PM 11156612 ER PT J AU Touchman, JW Dehejia, A Chiba-Falek, O Cabin, DE Schwartz, JR Orrison, BM Polymeropoulos, MH Nussbaum, RL AF Touchman, JW Dehejia, A Chiba-Falek, O Cabin, DE Schwartz, JR Orrison, BM Polymeropoulos, MH Nussbaum, RL TI Human and mouse alpha-synuclein genes: Comparative genomic sequence analysis and identification of a novel gene regulatory element SO GENOME RESEARCH LA English DT Article ID PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; MESSENGER-RNA; DNA; POLYMORPHISM; ASSIGNMENT; MUTATION AB The human alpha -synuclein gene (SNCA) encodes a presynaptic nerve terminal protein that was originally identified as a precursor of the non-beta -amyloid component of Alzheimer's disease plaques. More recently, mutations in SNCA have been identified in some cases of familial Parkinson's disease, presenting numerous new areas of investigation for this important disease. Molecular studies would benefit from detailed information about the long-range sequence context of SNCA. To that end, we have established the complete genomic sequence of the chromosomal regions containing the human and mouse alpha -synuclein genes, with the objective of using the resulting sequence information to identify conserved regions of biological importance through comparative sequence analysis. These efforts have yielded -146 and -119 kb of high-accuracy human and mouse genomic sequence, respectively, revealing the precise genetic architecture of the a-synuclein gene in both species. A simple repeat element upstream of SNCA/Snca has been identified and shown to be necessary For normal expression in transient transfection assays using a luciferase reporter construct. Together, these studies provide valuable data that should Facilitate more detailed analysis of this medically important gene. C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NIH, Intramural Sequencing Ctr, NIH, Gaithersburg, MD 20877 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. RP Nussbaum, RL (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NR 40 TC 81 Z9 84 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JAN PY 2001 VL 11 IS 1 BP 78 EP 86 DI 10.1101/gr.165801 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 391NH UT WOS:000166361700008 PM 11156617 ER PT J AU Myakishev, MV Khripin, Y Hu, S Hamer, DH AF Myakishev, MV Khripin, Y Hu, S Hamer, DH TI High-throughput SNP genotyping by allele-specific PCR with universal energy-transfer-labeled primers SO GENOME RESEARCH LA English DT Article ID POLYMERASE-CHAIN-REACTION; DNA DIAGNOSTIC METHOD; MUTATION SYSTEM ARMS; MOLECULAR BEACONS; OLIGONUCLEOTIDE PROBES; HYBRIDIZATION PROBES; AMPLIFICATION; POLYMORPHISM; ASSAY; FLUORESCENT AB We have developed a new method for high-throughput genotyping of single nucleotide polymorphisms (SNPs). The technique involves PCR amplification of genomic DNA with two tailed allele-specific primers that introduce priming sites for universal energy-transfer-labeled primers. The output of red and green light is conveniently scored using a fluorescence plate reader. The new method, which was validated on nine model SNPs, is well suited for high-throughput, automated genotyping because it requires only one reaction per SNP, it is performed in a single tube with no post-PCR handling, the same energy-transfer-labeled primers are used for ail analyses, and the instrumentation is inexpensive. Possible applications include multiple-candidate gene analysis, genomewide scans, and medical diagnostics. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Intergen Discovery Prod, Gaithersburg, MD 20877 USA. RP Myakishev, MV (reprint author), NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NR 34 TC 183 Z9 196 U1 4 U2 17 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JAN PY 2001 VL 11 IS 1 BP 163 EP 169 DI 10.1101/gr.157901 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 391NH UT WOS:000166361700016 PM 11156625 ER PT J AU Sahoo, T Goenaga-Diaz, E Serebriiskii, IG Thomas, JW Kotova, E Cuellar, JG Peloquin, JM Golemis, E Beitinjaneh, F Green, ED Johnson, EW Marchuk, DA AF Sahoo, T Goenaga-Diaz, E Serebriiskii, IG Thomas, JW Kotova, E Cuellar, JG Peloquin, JM Golemis, E Beitinjaneh, F Green, ED Johnson, EW Marchuk, DA TI Computational and experimental analyses reveal previously undetected coding exons of the KRIT1 (CCM1) gene SO GENOMICS LA English DT Article ID CEREBRAL CAVERNOUS MALFORMATIONS; CHROMOSOME 7Q; NATURAL-HISTORY; ENCODING KRIT1; YAC CONTIG; MUTATIONS; PROTEIN; MAPS AB A notable difficulty in annotating genomic sequence is identifying the correct start codon in a gene. An important such case has been found with KRIT1, the cerebral cavernous malformation type 1 (CCM1) gene. Analysis of human and mouse genomic sequence encompassing the region containing KRIT1/Krit1 using exon/gene-prediction and comparative alignment programs revealed putative exons upstream of the previously described first exon. These additional candidate exons show significant matches to mouse and human ESTs that are contiguous with and extend upstream from the previously designated 5' end of the KRIT1 cDNA sequence. RT-PCR and 5'RACE experiments confirm the presence of four additional upstream coding exons that encode an additional 207 amino acids. Importantly, a novel frameshift mutation in one of these newly identified KRIT1 exons has been found in a CCM1 family. These data establish the authentic KRIT1 amino acid sequence and suggest that the additional KRIT1 exons may harbor mutations in other CCM1 families. In addition, these results provide another example of the utility of rigorous computational and comparative sequence analysis for refining gene structure. (C) 2001 Academic Press. C1 Duke Univ, Med Ctr, Dept Genet, Durham, NC 27710 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Barrow Neurol Inst, Dept Neurogenet, Phoenix, AZ 85013 USA. Barrow Neurol Inst, Dept Neuropharmacol, Phoenix, AZ 85013 USA. Univ Hosp, Dept Neurol, Stony Brook, NY 11794 USA. SUNY Stony Brook, Hlth Sci Ctr, Stony Brook, NY 11794 USA. RP Marchuk, DA (reprint author), Duke Univ, Med Ctr, Dept Genet, Box 3175, Durham, NC 27710 USA. FU NCI NIH HHS [CA-06927] NR 15 TC 38 Z9 41 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 1 PY 2001 VL 71 IS 1 BP 123 EP 126 DI 10.1006/geno.2000.6426 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 394GH UT WOS:000166515300013 PM 11161805 ER PT J AU Volpato, S Zuliani, G Guralnik, JM Palmieri, E Fellin, R AF Volpato, S Zuliani, G Guralnik, JM Palmieri, E Fellin, R CA Gruppo Italiano Farmacovigilanza N TI The inverse association between age and cholesterol level among older patients: The role of poor health status SO GERONTOLOGY LA English DT Article DE low cholesterol; albumin; comorbidity; aging; epidemiology ID DENSITY-LIPOPROTEIN CHOLESTEROL; PLASMA-LIPIDS; CARDIOVASCULAR HEALTH; HOSPITALIZED-PATIENTS; ELDERLY MEN; HYPOCHOLESTEROLEMIA; WOMEN; DETERMINANTS; POPULATION; MORTALITY AB Background: The total cholesterol concentration decreases with age in older people. The reasons for this phenomenon are controversial. This study investigated the hypothesis that poor health status is a determinant of the inverse association between age and cholesterol in older persons. Methods: Cross-sectional study of 2,486 (53% women) older medical patients (greater than or equal to 65 years) admitted at 35 centers of the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) study in Italy. Total cholesterol was measured on the fi rst day after admission to the hospital. Disease burden and comorbidity were assessed by the Charlson index; low serum albumin and iron were considered markers of frailty and poor health. Results: In men there was a significant, inverse age-cholesterol relationship (-0.97 mg/dl per year, p < 0.001). In women the association was nonlinear and cholesterol significantly decreased after the age of 75 (-0.95 mg/dl per year, p < 0.005). In multiple linear regression analysis, indicators of poor health accounted for almost two thirds of the crude effect of age on the cholesterol level in both men and women (adjusted coefficients for age were: for men, -0.38 mg/dl per year, p = 0.044; for women after the age of 75, -0.37 mg/dl per year, p = 0.205). The unadjusted probability of having low cholesterol significantly increased with age among men (p for trend <0.005). In multiple logistic regression, indicators of poor health were strongly associated with low cholesterol in both men and women. After adjusting for indicators of poor health, the association between age and low cholesterol in men was no longer present. Conclusion: These findings suggest that the age-dependent reduction of cholesterol often observed in clinical and epidemiologic studies is substantially explained by the effect of poor health status. Low cholesterol in older persons may be a marker of poor health. Copyright <(c)> 2001 S. Karger AG,Basel. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Univ Ferrara, Sect Internal Med, Dept Clin & Expt Med 2, I-44100 Ferrara, Italy. RP Volpato, S (reprint author), NIA, Epidemiol Demog & Biometry Program, Gateway Bldg,Suite 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. RI VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 NR 37 TC 26 Z9 30 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0304-324X J9 GERONTOLOGY JI Gerontology PD JAN-FEB PY 2001 VL 47 IS 1 BP 36 EP 45 DI 10.1159/000052768 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 415DA UT WOS:000167704400006 PM 11244290 ER PT J AU Seko, Y Pang, JJ Tokoro, T Ichinose, S Mochizuki, M AF Seko, Y Pang, JJ Tokoro, T Ichinose, S Mochizuki, M TI Blue light-induced apoptosis in cultured retinal pigment epithelium cells of the rat SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID PHOTOCHEMICAL LESIONS; MACULAR DEGENERATION; ENDOTHELIAL-CELLS; VISIBLE-LIGHT; DAMAGE; DEATH; SENSITIVITY; MECHANISMS; EXPOSURE; OXYGEN AB Background: We previously demonstrated that phagosome-free retinal pigment epithelium (RPE) cells in culture can be damaged directly by blue light (wavelength 440+/-10 nm) as observed by electron microscope. A low intensity (1.0 mW/cm(2)) of light induced only swelling of mitochondria, while a high intensity (4.0 mW/cm(2)) induced necrosis in the RPE. The aim of the present study was to investigate what intensity of blue light could induce apoptosis in cultured phagosome-free RPE. Methods: Primary cultured RPE cells, harvested from Long-Evans rats, that contained no phagosomes were exposed to a cool blue light (wavelength 440+/-10 nm). After exposure, transmission electron microscopy (TEM) and TdT-mediated dUTP nick-end labeling (TUNEL) staining were used to detect apoptosis in the RPE cells. To assess the relationship of oxidation to apoptosis by blue light, we added N-acetylcysteine (NAC) as a free radical scavenger and investigated its inhibitory effect on apoptosis. Results: In RPE cells exposed to blue light of 2.7 mW/cm(2) for 24 h, apoptotic bodies were found by TEM. In RPE cells exposed to blue light of 2.0 mW/cm(2) for 60 h, apoptotic bodies, nuclear condensation and nuclear segmentation were observed by TEM and some RPE cells showed positive TUNEL staining. When 30 mM of NAC was added, TUNEL staining was negative. Conclusion: Our findings demonstrate that apoptotic cell death is induced by blue light exposure in cultured RPE cells in vitro. The findings of our previous experiments and those of the present study suggest that a higher intensity of blue light could induce necrosis, and moderately intense blue light could induce non-necrotic cell death or apoptosis, in RPE cells. Furthermore, it is suggested that blue light caused cell death by a free-radical-associated mechanism. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Tokyo Med & Dent Univ, Grad Sch, Dept Ophthalmol & Visual Sci, Tokyo, Japan. Tokyo Med & Dent Univ, Grad Sch, Instrumental Anal Res Ctr Life Sci, Tokyo, Japan. RP Seko, Y (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Rm 10N113,10 Ctr Dr,MSC-1857, Bethesda, MD 20892 USA. NR 32 TC 21 Z9 27 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD JAN PY 2001 VL 239 IS 1 BP 47 EP 52 DI 10.1007/s004170000220 PG 6 WC Ophthalmology SC Ophthalmology GA 398DM UT WOS:000166741400008 PM 11271461 ER PT J AU Lipkus, IM Biradavolu, M Fenn, K Keller, P Rimer, BK AF Lipkus, IM Biradavolu, M Fenn, K Keller, P Rimer, BK TI Informing women about their breast cancer risks: Truth and consequences SO HEALTH COMMUNICATION LA English DT Article ID SERVING SOCIAL COMPARISONS; FIRST-DEGREE RELATIVES; PSYCHOLOGICAL DISTRESS; UNREALISTIC OPTIMISM; SELF-EXAMINATION; FAMILY HISTORY; HEALTH-PROBLEMS; PERCEIVED RISK; SUSCEPTIBILITY; PERCEPTIONS AB We assessed the extent to which informing women about their risk for breast cancer affected their perceived 10-year and lifetime risks for getting breast cancer, their emotional reactions toward getting breast cancer, and their intentions to get mammograms. In a pre- to posttest design, 121 women were given their 10-year risk of getting breast cancer with or without being compared with women their age and race at lowest risk. Women's perceptions of their 10-year risks became more congruent (i.e., more accurate) with their actual risk. Participants were more accurate when they received their own risk without being compared with women at lowest risk. Women who received only their own risk estimate reported being at lower risk than other women. Overall, women reported that obtaining their 10-year risk estimate either did not affect or increased their intentions to get mammograms. These results suggest that giving women their individual risk of getting breast cancer improves accuracy while also enhancing their feelings that they are at lower risk than other women. Counter to many theories of health behavior, reducing women's perceived risk of breast cancer did not lower their intentions to get mammograms. Implications for the communication of breast cancer risk are discussed. C1 Duke Univ, Med Ctr, Canc Prevent Detect & Control Res Program, Durham, NC USA. NCI, Bethesda, MD 20892 USA. RP Lipkus, IM (reprint author), 905 W Main St,Box 34, Durham, NC USA. FU NCI NIH HHS [5U19CA72099-04] NR 51 TC 58 Z9 58 U1 1 U2 6 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1041-0236 J9 HEALTH COMMUN JI Health Commun. PY 2001 VL 13 IS 2 BP 205 EP 226 DI 10.1207/S15327027HC1302_5 PG 22 WC Communication; Health Policy & Services SC Communication; Health Care Sciences & Services GA 449CV UT WOS:000169667500005 PM 11451105 ER PT S AU Stadtman, ER AF Stadtman, ER BE Park, SC Hwang, ES Kim, HS Park, WY TI Protein oxidation in aging and age-related diseases SO HEALTHY AGING FOR FUNCTIONAL LONGEVITY: MOLECULAR AND CELLULAR INTERACTIONS IN SENESCENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Healthy Aging for Functional Longevity CY FEB, 2000 CL KYONGJU, SOUTH KOREA SP Federat Korean Gerontol Soc, Int Assoc BioMed Gerontol, Korea Sci & Engn Fdn, Korea Res Fdn, Korea Res Fdn Hlth Sci, Seoul Natl Univ DE oxidatively modified protein; reactive oxygen species; amino acid residues; apoptosis ID METAL-CATALYZED OXIDATION; METHIONINE SULFOXIDE REDUCTASE; MIXED-FUNCTION OXIDATION; LOW-DENSITY LIPOPROTEINS; GLYCATION END-PRODUCTS; NITRIC-OXIDE SYNTHASE; BOVINE SERUM-ALBUMIN; AMINO-ACID-RESIDUES; LIPID-PEROXIDATION; CARBON-DIOXIDE AB Although different theories have been proposed to explain the aging process, it is generally agreed that there is a correlation between aging and the accumulation of oxidatively damaged proteins, lipids, and nucleic acids. Oxidatively modified proteins have been shown to increase as a function of age. Studies reveal an age-related increase in the level of protein carbonyl content, oxidized methionine, protein hydrophobicity, and cross-linked and glycated proteins as well as the accumulation of less active enzymes that are more susceptible to heat inactivation and proteolytic degredation. Factors that decelerate protein oxidation also increase the life span of animals and vice versa. Furthermore, a number of age-related diseases have been shown to be associated with elevated levels of oxidatively modified proteins. The chemistry of reactive oxygen species-mediated protein modification will be discussed. The accumulation of oxidatively modified proteins may reflect deficiencies in one or more parameters of a complex function that maintains a delicate balance between the presence of a multiplicity of prooxidants, antioxidants, and repair, replacement, or elimination of biologically damaged proteins. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3,Room 222,3 Ctr Dr,MSC-0342, Bethesda, MD 20892 USA. NR 135 TC 378 Z9 390 U1 5 U2 25 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-285-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 928 BP 22 EP 38 PG 17 WC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Science & Technology - Other Topics GA BT10T UT WOS:000171969700002 PM 11795513 ER PT S AU Yim, MB Yim, HS Lee, C Kang, SO Chock, PB AF Yim, MB Yim, HS Lee, C Kang, SO Chock, PB BE Park, SC Hwang, ES Kim, HS Park, WY TI Protein glycation - Creation of catalytic sites for free radical generation SO HEALTHY AGING FOR FUNCTIONAL LONGEVITY: MOLECULAR AND CELLULAR INTERACTIONS IN SENESCENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Healthy Aging for Functional Longevity CY FEB, 2000 CL KYONGJU, SOUTH KOREA SP Federat Korean Gerontol Soc, Int Assoc BioMed Gerontol, Korea Sci & Engn Fdn, Korea Res Fdn, Korea Res Fdn Hlth Sci, Seoul Natl Univ DE nonenzymatic glycosylation; Maillard reaction; methylglyoxal ID HUMAN LENS PROTEINS; MAILLARD REACTION; CROSS-LINK; PHYSIOLOGICAL CONDITIONS; HUMAN COLLAGEN; IN-VIVO; METHYLGLYOXAL; GLYCOSYLATION; MECHANISM; GLUCOSE AB In a glycation reaction, alpha -dicarbonyl compounds such as deoxyglucosone, methylglyoxal, and glyoxal are more reactive than the parent sugars with respect to their ability to react with amino groups of proteins to form inter-and intramolecular cross-links of proteins, stable end products called advanced Maillard products or advanced end products (AGEs). The AGES, which are irreversibly formed, accumulate with aging, atherosclerosis, and diabetes mellitus, and are especially associated with long-lived proteins such as collagens, lens crystallins, and nerve proteins. It was suggested that the formation of AGEs not only modifies protein properites but also induces biological damage in vivo. In this report, we summerize results obtained from our studies for (1) identifying the structure of the cross-linked radical species formed in the model system-the reaction between alpha -dicarbonyl methylglyoxal with amino acids, and (2) the reactivity of the radical center of the protein created by the similar reaction. These results indicate that glycation of protein generates active centers for catalyzing one-electron oxidation-reduction reactions. This active center, which exhibits enzyme-like character, is suggested to be the crosslinked Schiff-based radical cation of the protein. It mimics the characteristics of the metal-catalyzed oxidation system. These results together indicate that glycated proteins accumulated in vivo provide stable active sites for catalyzing the formation of free redicals. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Nat Sci, Dept Microbiol, Biophys Lab, Seoul 151742, South Korea. Seoul Natl Univ, Res Ctr Mol Microbiol, Seoul 151742, South Korea. RP Yim, MB (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3, Bethesda, MD 20892 USA. NR 27 TC 106 Z9 117 U1 1 U2 10 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-285-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 928 BP 48 EP 53 PG 6 WC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Science & Technology - Other Topics GA BT10T UT WOS:000171969700004 PM 11795527 ER PT S AU Lane, MA Black, A Handy, A Tilmont, EM Ingram, DK Roth, GS AF Lane, MA Black, A Handy, A Tilmont, EM Ingram, DK Roth, GS BE Park, SC Hwang, ES Kim, HS Park, WY TI Caloric restriction in primates SO HEALTHY AGING FOR FUNCTIONAL LONGEVITY: MOLECULAR AND CELLULAR INTERACTIONS IN SENESCENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Healthy Aging for Functional Longevity CY FEB, 2000 CL KYONGJU, SOUTH KOREA SP Federat Korean Gerontol Soc, Int Assoc BioMed Gerontol, Korea Sci & Engn Fdn, Korea Res Fdn, Korea Res Fdn Hlth Sci, Seoul Natl Univ DE increasing life span; insulin levels; primates; rodent models ID MALE RHESUS-MONKEYS; DIETARY RESTRICTION; MACACA-MULATTA; NONHUMAN-PRIMATES; BLOOD-CHEMISTRY; BIOMARKERS; HEMATOLOGY; RISK AB Caloric restriction (CR) remains the only nongenetic intervention that reproducibly extends mean and maximal life span in short-lived mammalian species. This nutritional intervention also delays the onset, or slows the progression, of many age-related disease processes. The diverse effects of CR have been demonstrated many hundreds of times in laboratory rodents and other short-lived species, such as rotifers, water fleas, fish, spiders, and hamsters. Until recently, the effects of CR in longer-lived species, more closely related to humans, remained unknown. Long-term studies of aging in nonhuman primates undergoing CR have been underway at the National Institute on Aging (NIA) and the University of Wisconsin-Madison (UW) for over a decade. A number of reports from the NIA and UW colonies have shown that monkeys on CR exhibit nearly identical physiological responses as reported in laboratory rodents. Studies of various markers related to age-related diseases suggest that CR will prevent or delay the onset of cardiovascular disease, diabetes, and perhaps cancer, and preliminary data indicate that mortality due to these and other age-associated diseases may also be reduced in monkeys on CR, compared to controls. Conclusive evidence showing that CR extends life span in primates is not presently available; however, the emerging data from the ongoing primate studies strengthens the possibility that the diverse beneficial effects of CR on aging in rodents will also apply to nonhuman primates and perhaps ultimately to humans. C1 NIA, Neurosci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Lane, MA (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 25 TC 70 Z9 71 U1 0 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-285-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 928 BP 287 EP 295 PG 9 WC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Science & Technology - Other Topics GA BT10T UT WOS:000171969700028 PM 11795520 ER PT S AU Roth, GS Ingram, DK Lane, MA AF Roth, GS Ingram, DK Lane, MA BE Park, SC Hwang, ES Kim, HS Park, WY TI Caloric restriction in primates and relevance to humans SO HEALTHY AGING FOR FUNCTIONAL LONGEVITY: MOLECULAR AND CELLULAR INTERACTIONS IN SENESCENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Healthy Aging for Functional Longevity CY FEB, 2000 CL KYONGJU, SOUTH KOREA SP Federat Korean Gerontol Soc, Int Assoc BioMed Gerontol, Korea Sci & Engn Fdn, Korea Res Fdn, Korea Res Fdn Hlth Sci, Seoul Natl Univ DE caloric restriction; primates; humans ID METFORMIN; GLUCOSE; MICE AB Dietary caloric restriction (CR) is the only intervention conclusively and reproducibly shown to slow aging and maintain health and vitality in mammals. Although this paradigm has been known for ever 60 years, its precise biological mechanisms and applicability to humans remain unknown. We began addressing the latter question in 1987 with the first controlled study of CR in primates (rhesus and squirrel monkeys, which are evolutionarily much closer to humans than the rodents most frequently employed in CR studies). To date, our results strongly suggest that the same beneficial "antiaging" and/or "antidisease" effects observed in CR rodents also occur in primates. These include lower plasma insulin levels and greater sensitivity; lower body temperatures; reduced cholesterol, triglycerides, blood pressure, and arterial stiffness; elevated HDL; and slower age-related decline in circulating levels of DHEAS. Collectively, these biomarkers suggest that CR primates will be less likely to incur diabetes, cardiovascular problems, and other age-related diseases and may in fact be aging more slowly than fully fed counterparts. Despite these very encouraging results, it is unlikely that most humans would be willing to maintain a 30% reduced diet for the bulk of their adult life span, even if it meant more healthy years. For this reason, we have begun to explore CR mimetics, agents that might elicit the same beneficial effects as CR, without the necessity of dieting. Our initial studies have focused on 2-deoxyglucose (2DG), a sugar analogue with a limited metabolism that actually reduces glucose/energy flux without decreasing food intake in rats. In a six-month pilot study, 2DG lowered plasma insulin and body temperature in a manner analagous to that of CR. Thus, metabolic effects that mediate the CR mechanism can be attained pharmacologically. Doses were titrated to eliminate toxicity; a longterm longevity study is now under way. In addition, data from other laboratories suggest that at least some of the same physiological/metabolic end points that are associated with the beneficial effects of underfeeding may be obtained from other potential CR mimetic agents, some naturally occurring in food products. Much work remains to be done, but taken together, our successful results with CR in primates and 2DG administration to rats suggest that it may indeed be possible to obtain the health- and longevity-promoting effects of the former intervention without actually decreasing food intake. C1 NIA, Neurosci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Roth, GS (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 18 TC 151 Z9 157 U1 2 U2 14 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-285-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 928 BP 305 EP 315 PG 11 WC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Science & Technology - Other Topics GA BT10T UT WOS:000171969700030 PM 11795522 ER PT S AU Ingram, DK Chefer, S Matochik, J Moscrip, TD Weed, J Roth, GS London, ED Lane, MA AF Ingram, DK Chefer, S Matochik, J Moscrip, TD Weed, J Roth, GS London, ED Lane, MA BE Park, SC Hwang, ES Kim, HS Park, WY TI Aging and caloric restriction in nonhuman primates - Behavioral and in vivo brain imaging studies SO HEALTHY AGING FOR FUNCTIONAL LONGEVITY: MOLECULAR AND CELLULAR INTERACTIONS IN SENESCENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Healthy Aging for Functional Longevity CY FEB, 2000 CL KYONGJU, SOUTH KOREA SP Federat Korean Gerontol Soc, Int Assoc BioMed Gerontol, Korea Sci & Engn Fdn, Korea Res Fdn, Korea Res Fdn Hlth Sci, Seoul Natl Univ DE locomotor activity; MRI; PET; basal ganglia; putamen; caudate nucleus ID AGE-RELATED-CHANGES; DIETARY RESTRICTION; RHESUS-MONKEYS; DOPAMINE-RECEPTORS; C-11 RACLOPRIDE; FISCHER-344 RATS; HUMAN STRIATUM; MOTOR; DECLINE; MATTER AB In a long-term longitudinal study of aging in rhesus monkeys, a primary objective has been to determine the effects of aging and caloric restriction (CR) on behavioral and neural parameters. Through the use of automated devices, locomotor activity can be monitored in the home cages of the monkeys. Studies completed thus far indicate a clear age-related decline in activity consistent with such observations in many other species, including humans. However, no consistent effects of CR on activity have been observed. Selected groups of monkeys have also been involved in brain imaging studies, using magnetic resonance imaging (MRI) and positron emission tomography (PET). MRI studies completed thus far reveal a clear age-related decline in the volumes of the basal ganglia, the putamen, and the caudate nucleus, with no change in total brain volume. PET analysis has revealed an age-related decline in the binding potential of dopamine D-2 receptors in the same brain regions. These results are consistent with findings in humans. Although additional longitudinal analysis is needed to confirm the present results, it would appear that locomotor activity, volume of the basal ganglia, as well as dopamine D-2 receptor binding potential provide reliable, noninvasive biomarkers of aging in rhesus monkeys. C1 NIA, Neurosci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NIDA, Neuroimaging Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Columbia Univ, Dept Psychol, New York, NY 10027 USA. NIH, Off Res Serv, Vet Resources Program, Bethesda, MD 20892 USA. RP Ingram, DK (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 50 TC 20 Z9 21 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-285-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 928 BP 316 EP 326 PG 11 WC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Science & Technology - Other Topics GA BT10T UT WOS:000171969700031 PM 11795523 ER PT S AU Park, SC Kitani, K Yu, BP Ingram, DK Reznick, A Goto, S Roth, GS Zs-Nagy, I Meydani, M Vijg, J Harmon, D Stadtman, E AF Park, SC Kitani, K Yu, BP Ingram, DK Reznick, A Goto, S Roth, GS Zs-Nagy, I Meydani, M Vijg, J Harmon, D Stadtman, E BE Park, SC Hwang, ES Kim, HS Park, WY TI Panel discussion - Perspectives in aging research in the new millennium SO HEALTHY AGING FOR FUNCTIONAL LONGEVITY: MOLECULAR AND CELLULAR INTERACTIONS IN SENESCENCE SE Annals of the New York Academy of Sciences LA English DT Editorial Material CT Conference on Healthy Aging for Functional Longevity CY FEB, 2000 CL KYONGJU, SOUTH KOREA SP Federat Korean Gerontol Soc, Int Assoc BioMed Gerontol, Korea Sci & Engn Fdn, Korea Res Fdn, Korea Res Fdn Hlth Sci, Seoul Natl Univ C1 Seoul Natl Univ, Coll Med, Seoul 151, South Korea. Natl Inst Longev Sci, Aichi, Japan. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. NIA, Baltimore, MD 21224 USA. Technion Israel Inst Technol, Haifa, Israel. Toho Univ, Chiba 2748510, Japan. NIA, Baltimore, MD 21224 USA. Univ Debrecen, H-4012 Debrecen, Hungary. Tufts Univ, Medford, MA 02155 USA. Inst Drug Dev, San Antonio, TX USA. Univ Nebraska, Coll Med, Omaha, NE 68198 USA. NHLBI, Bethesda, MD 20892 USA. RP Park, SC (reprint author), Seoul Natl Univ, Coll Med, Seoul 151, South Korea. NR 0 TC 1 Z9 1 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-285-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 928 BP 336 EP 343 PG 8 WC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Science & Technology - Other Topics GA BT10T UT WOS:000171969700033 PM 11795525 ER PT S AU Jeong, BH Jin, JK Choi, EK Meeker, HC Kozak, CA Carp, RI Kim, YS AF Jeong, BH Jin, JK Choi, EK Meeker, HC Kozak, CA Carp, RI Kim, YS BE Park, SC Hwang, ES Kim, HS Park, WY TI Analysis of the cell distribution of endogenous murine leukemia virus in the brains of SAMR1 and SAMP8 mice SO HEALTHY AGING FOR FUNCTIONAL LONGEVITY: MOLECULAR AND CELLULAR INTERACTIONS IN SENESCENCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Healthy Aging for Functional Longevity CY FEB, 2000 CL KYONGJU, SOUTH KOREA SP Federat Korean Gerontol Soc, Int Assoc BioMed Gerontol, Korea Sci & Engn Fdn, Korea Res Fdn, Korea Res Fdn Hlth Sci, Seoul Natl Univ C1 Hallym Acad Sci, Inst Environm & Life Sci, Chunchon 200702, Kangwon Do, South Korea. Hallym Univ, Coll Med, Dept Microbiol, Chunchon 200702, Kangwon Do, South Korea. New York State Inst Basic Res Dev Disabil, Dept Virol, Staten Isl, NY 10314 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Jeong, BH (reprint author), Hallym Acad Sci, Inst Environm & Life Sci, Chunchon 200702, Kangwon Do, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-285-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 928 BP 347 EP 347 PG 1 WC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Geriatrics & Gerontology; Science & Technology - Other Topics GA BT10T UT WOS:000171969700037 ER PT J AU Sigmon, HD Grady, PA AF Sigmon, HD Grady, PA TI Quality of life for transplantation patients: National Institute of Nursing Research Spring Science Work Group SO HEART & LUNG LA English DT Article AB Quality of life for transplantation patients offers many opportunities for basic science and clinical researchers, ranging from biological and behavioral investigations to clinical interventions and population studies. Specific topics of interest for the field of transplantation research that have immediate application to studies of duality of life include signs and symptoms of chronic illness, biobehavioral risk factors for disease, functional disabilities, patient outcomes, adherence to treatment, care delivery roles of families and caregivers, strategies of stress management, special needs of children and high-risk patients. health promotion and education, and long-term care. These topics offer investigators a unique opportunity to develop and apply integrated prevention and treatment strategies and to contribute valuable insights and skills ro multidisciplinary research teams needed for quality-of-life studies of transplantation patients. C1 NINR, NIH, Bethesda, MD 20892 USA. RP Sigmon, HD (reprint author), NINR, NIH, Bldg 45,Room 3AN12,MSC 6300, Bethesda, MD 20892 USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0147-9563 J9 HEART LUNG JI Heart Lung PD JAN-FEB PY 2001 VL 30 IS 1 BP 5 EP 8 DI 10.1067/mhl.2001.111728 PG 4 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA 394NW UT WOS:000166531000002 PM 11174362 ER PT S AU Orlic, D Kajstura, J Chimenti, S Bodine, DM Leri, A Anversa, P AF Orlic, D Kajstura, J Chimenti, S Bodine, DM Leri, A Anversa, P BE Orlic, D Brummendorf, TH Sharkis, SJ Kanz, L TI Transplanted adult bone marrow cells repair myocardial infarcts in mice SO HEMATOPOIETIC STEM CELLS 2000 BASIC AND CLINICAL SCIENCES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Conference on Hematopoietic Stem Cells: Genetics and Medicine CY SEP 14-16, 2000 CL TUBINGEN, GERMANY SP AMGEN, KIRIN DE stein cells; bone marrow; myocardial regeneration ID C-KIT; EXPRESSION; POPULATIONS AB Occlusion of the anterior descending left coronary artery leads to ischemia, infarction, and loss of function in the left ventricle. We have studied the repair of infarcted myocardium in mice using highly enriched stem/progenitor cells from adult bone marrow. The left coronary artery was ligated and 5 hours later Lin(-) c-kit(+) bone marrow cells obtained from transgenic male mice expressing enhanced green fluorescent protein (EGFP) were injected into the healthy myocardium adjacent to the site of the infarct. After 9 days the damaged hearts were examined for regenerating myocardium. A band of new myocardium was observed in 12 surviving mice. The developing myocytes were small and resembled fetal and neonatal myocytes. They were positive for EGFP, Y chromosome, and several myocyte-specific proteins including cardiac myosin, and the transcription factors GATA-4, MEF2, and Csx/Nkx2.5. The cells were also positive for connexin 43, a gap junction/intercalated disc component indicating the onset of intercellular communication. Myocyte proliferation was demonstrated by incorporation of BrdU into the DNA of dividing cells and by the presence of the cell cycle-associated protein Ki67 in their nuclei. Neo-vascularization was also observed in regenerating myocardium. Endothelial and smooth muscle cells in developing capillaries and small arterioles were EGFP-positive. These cells were positive for Factor VIII and alpha smooth muscle actin, respectively. No myocardial regeneration was observed in damaged hearts transplanted with Lin(-) c-kit(-) bone marrow cells, which lack bone marrow-regenerating activity. Functional competence of the repaired left ventricle was improved for several hemodynamic parameters. These in vivo findings demonstrate the capacity of highly enriched Lin(-) c-kit(+) adult bone marrow cells to acutely regenerate functional myocardium within an infarcted region. C1 NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. New York Med Coll, Dept Med, Valhalla, NY 10595 USA. RP Orlic, D (reprint author), NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bldg 49,Room 3W16,49 Convent Dr, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [HL-38132, HL-39902, HL-43023, HL-65577, HL-66923]; NIA NIH HHS [AG-15756, AG-17042] NR 19 TC 290 Z9 332 U1 1 U2 10 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-295-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 938 BP 221 EP 230 PG 10 WC Cell Biology; Multidisciplinary Sciences SC Cell Biology; Science & Technology - Other Topics GA BT12U UT WOS:000172028500025 PM 11458511 ER PT S AU Dunbar, CE Takatoku, M Donahue, RE AF Dunbar, CE Takatoku, M Donahue, RE BE Orlic, D Brummendorf, TH Sharkis, SJ Kanz, L TI The impact of ex vivo cytokine stimulation on engraftment of primitive hematopoietic cells in a non-human primate model SO HEMATOPOIETIC STEM CELLS 2000 BASIC AND CLINICAL SCIENCES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Conference on Hematopoietic Stem Cells: Genetics and Medicine CY SEP 14-16, 2000 CL TUBINGEN, GERMANY SP AMGEN, KIRIN DE stem cells; cell cycle; homing ID BLOOD CD34(+) CELLS; STEM-CELL; NONHUMAN-PRIMATES; PROGENITOR CELLS; REPOPULATING CELLS; GENE-TRANSFER; CYCLE STATUS; TRANSDUCTION; EXPANSION; FIBRONECTIN AB The impairment of engraftment ability after ex vivo or in vivo stimulation of hematopoietic stem cells, potentially related to induction of active cell cycling, has recently been a topic of intense interest. Our group has used the non-human primate autologous transplantation model and genetic marking to investigate a number of questions in hematopoiesis with direct relevance to human clinical applications. The issue of a potential reversible engraftment defect would have many implications for gene therapy and allogeneic or autologous transplantation. Initial in vitro studies with rhesus CD34(+) cells indicated that after 4 days of stimulatory culture in stem cell factor (SCF), megakaryocyte growth and development factor (MDGF), and flt3 ligand (FLT), transfer of the cells to SCF alone on retronectin (FN) support resulted in decreased active cycling and a halt to proliferation, without a loss of viability or induction of apoptosis. We then directly compared the engraftment potential of cytokine-stimulated cells versus those transferred to SCF on FN alone before reinfusion, SCF/G-CSF mobilized CD34(+) cells from three animals were split into two parts and transduced with either of two retroviral marking vectors for 4 days in the presence of SCF/FLT/MGDF on FN. One aliquot was cryopreserved, and the other was continued in culture without transduction for 2 days in the presence of SCF alone on FN. After total body irradiation, both aliquots were thawed and reinfused into each animal. In all animals, the level of marking from the fraction continued in culture for 2 days with SCF on FN was significantly higher than the level of marking from the aliquot transduced for 4 days without the 2-day period in SCF alone. This approach may allow more efficient engraftment of successfully transduced or ex vivo expanded cells by avoiding active cell cycling at the time of reinfusion. C1 NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Dunbar, CE (reprint author), NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 20 TC 19 Z9 21 U1 1 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-295-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 938 BP 236 EP 245 PG 10 WC Cell Biology; Multidisciplinary Sciences SC Cell Biology; Science & Technology - Other Topics GA BT12U UT WOS:000172028500027 PM 11458513 ER PT S AU Sabatino, DE Seidel, NE Cline, AP Anderson, SM Gallagher, PG Bodine, DM AF Sabatino, DE Seidel, NE Cline, AP Anderson, SM Gallagher, PG Bodine, DM BE Orlic, D Brummendorf, TH Sharkis, SJ Kanz, L TI Development of a stable retrovirus vector capable of long-term expression of gamma-globin mRNA in mouse erythrocytes SO HEMATOPOIETIC STEM CELLS 2000 BASIC AND CLINICAL SCIENCES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Conference on Hematopoietic Stem Cells: Genetics and Medicine CY SEP 14-16, 2000 CL TUBINGEN, GERMANY SP AMGEN, KIRIN DE gene therapy; globin; retrovirus; ankyrin ID HUMAN BETA-GLOBIN; HEMATOPOIETIC STEM-CELLS; LOCUS-CONTROL REGION; HIGH-LEVEL EXPRESSION; TRANSGENIC MICE; GENE-THERAPY; POSITION; PROMOTER; HEMOGLOBINOPATHIES; SITE-2 AB Gene therapy for patients with hemoglobin disorders such has been hampered by the inability of retrovirus vectors to transfer globin genes and the locus control region (LCR) into hematopoietic stem cells without rearrangement. In addition, the expression from intact globin gene vectors has been variable in red blood cells as a result of position effects and retrovirus silencing. We hypothesized that by substituting the globin gene promoter for the promoter of another gene expressed in red blood cells, we could generate stable retrovirus vectors that would express globin at sufficient levels to treat hemoglobinopathies. Transgenic mice containing the human ankyrin (Ank) gene promoter fused to the human gamma -globin gene showed position-independent, copy number-dependent expression of a linked gamma -globin mRNA. We generated a "double-copy" Ank/(A) gamma -globin retrovirus vector that transferred two copies of the Ank/(A)-gamma -globin gene into target cells. Stable gene transfer was observed in primary primary mouse progenitor cells and long-term repopulating hematopoietic stem cells. Expression of Ank/(A)gamma -globin mRNA in mature red blood cells was approximately 8% of the level of mouse alpha -globin mRNA. We conclude that this novel retrovirus vector may be valuable for treating a variety of hemoglobinopathies by gene therapy if the level of expression can be further increased. C1 NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. RP Bodine, DM (reprint author), NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bldg 49,Room 3A14 MSC 4442, Bethesda, MD 20892 USA. NR 36 TC 6 Z9 7 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-295-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 938 BP 246 EP 261 PG 16 WC Cell Biology; Multidisciplinary Sciences SC Cell Biology; Science & Technology - Other Topics GA BT12U UT WOS:000172028500028 PM 11458514 ER PT S AU Brummendorf, TH Rufer, N Holyoake, TL Maciejewski, J Barnett, MJ Eaves, CJ Eaves, AC Young, N Lansdorp, PM AF Brummendorf, TH Rufer, N Holyoake, TL Maciejewski, J Barnett, MJ Eaves, CJ Eaves, AC Young, N Lansdorp, PM BE Orlic, D Brummendorf, TH Sharkis, SJ Kanz, L TI Telomere length dynamics in normal individuals and in patients with hematopoietic stem cell-associated disorders SO HEMATOPOIETIC STEM CELLS 2000 BASIC AND CLINICAL SCIENCES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Conference on Hematopoietic Stem Cells: Genetics and Medicine CY SEP 14-16, 2000 CL TUBINGEN, GERMANY SP AMGEN, KIRIN DE telomeres; chronic myelogenous leukemia; flow cytometry; bone marrow failure ID CHRONIC MYELOID-LEUKEMIA; APLASTIC-ANEMIA; BONE-MARROW; BLOOD-CELLS; FLOW-CYTOMETRY; FETAL LIVER; LIFE-SPAN; DNA; AGE; CULTURE AB The telomere length in nucleated peripheral blood (PB) cells indirectly reflects the mitotic history of their precursors: the hematopoietic stem cells (HSCs). The average length of telomeres in PB leukocytes can be measured using fluorescence in situ hybridization and flow cytometry (flow FISH). We previously used flow FISH to characterize the age-related turnover of HSCs in healthy individuals. In this review, we describe results of recent flow FISH studies in patients with selected hematopoietic stem cell-associated disorders: chronic myelogeneous leukemia (CML) and several bone marrow failure syndromes. CML is characterized by a marked expansion of myeloid Philadelphia chromosome positive (Ph+) cells. Nevertheless, nonmalignant (Ph-) HSCs typically coexist in the bone marrow of CML patients. We analyzed the telomere length in > 150 peripheral blood leukocytes (PBLs) and bone marrow samples of patients with CML as well as samples of Ph- T-lymphocytes. Compared to normal controls, the overall telomere fluorescence in PBLs of patients with CML was significantly reduced. However, no telomere shortening was observed in Ph- T-lymphocytes. Patients in late chronic phase (CP) had significantly shorter telomeres than those assessed earlier in CP. Our data suggest that progressive telomere shortening is correlated with disease progression in CML. Within the group of patients with bone marrow failure syndromes, we only found significantly shortened telomeres (compared to age-adjusted controls) in granulocytes from patients with aplastic anemia (AA). Strikingly, the telomere length in granulocytes from AA patients who had recovered after immunosuppressive therapy (recAA) did not differ significantly from controls, whereas untreated patients and nonresponders with persistent severe pancytopenia (sAANR) showed marked and significant telomere shortening compared to healthy donors and patients with recAA. Furthermore, an inverse correlation between age-adjusted telomere length and peripheral blood counts was found in support of a model in which the degree of cytopenia and the amount of telomere shortening are correlated. These results support the concept of extensive proliferation of HSCs in subgroups of AA patients and suggest a potential use of telomere-length measurements as a prognostic tool in this group of disorders as well. C1 Univ Tubingen, Dept Hematol Oncol & Immunol, D-72076 Tubingen, Germany. British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. Univ Geneva, Div Immunol & Allergol, Geneva, Switzerland. NIH, Hematol Branch, Bethesda, MD 20892 USA. RP Brummendorf, TH (reprint author), Univ Tubingen, Dept Hematol Oncol & Immunol, Otfried Muller Str 10, D-72076 Tubingen, Germany. NR 65 TC 52 Z9 56 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-295-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 938 BP 293 EP 304 PG 12 WC Cell Biology; Multidisciplinary Sciences SC Cell Biology; Science & Technology - Other Topics GA BT12U UT WOS:000172028500031 PM 11458518 ER PT J AU Rigano, P Rodgers, GP Renda, D Renda, MC Aquino, A Maggio, A AF Rigano, P Rodgers, GP Renda, D Renda, MC Aquino, A Maggio, A TI Clinical and hematological responses to hydroxyurea in sicilian patients with Hb S/beta-thalassemia SO HEMOGLOBIN LA English DT Article ID SICKLE-CELL DISEASE; SC DISEASE; ANEMIA; CHILDREN; HEMOGLOBIN; THERAPY AB Although, several reports have detailed that hydroxyurea can ameliorate the clinical course of adult and pediatric patients with sickle cell anemia (Hb S or betaS), few clinical studies have been carried out in patients with beta (S)/beta -thalassemia. In a two-year clinical study, we evaluated the efficacy of hydroxyurea in a group of 22 adult Sicilian patients with beta (S)/beta -thaiassemia with severe phenotypes. Among the 20 patients evaluated during 2 years of treatment, we observed a very good clinical response with a 93% reduction of the annual number of crises (median 7 versus 0.5 crises per year; P < 0.001) and of days in hospital (mean 22 +/- 21.9 versus 1.2 +/-2.3; P < 0.001), a significant increase in Hb F (7.5 +/-5.3% versus 25.2 +/-5.2%; P < 0.001) and in MCV (73.1 +/-4.8 f L versus 96.4 +/-7.2 f L; P < 0.001), and no significant modifications in Hb (9.6 +/-1.3 g/dL versus 10.0 +/-1.5 g/dL; P > 0.05) and in WBC (11.4 +/-3.9 x 10(9)/L versus 10.2 +/-3.9 x 10(9)/L; P > 0.05). Twelve patients had no crises from the first month of treatment; 16 patients showed a 2-3-fold increase over baseline in Hb F During the study no severe complications and no important side effects of hydroxyurea were observed. Our data suggest that hydroxyurea efficacy in patients with beta (S)/beta -thalassemial may be greater than that described in patients with sickle cell disease. This pattern and durability of response will need to be confirmed ill a larger, randomized, clinical trial. C1 Osped V Cervello, Serv Prevenz & Terapia Talassemia, Unita Ric Piera Cutino, Thalassaemia Ctr, I-90147 Palermo, Italy. NIH, Mol & Clin Hematol Branch, Bethesda, MD 20892 USA. RP Rigano, P (reprint author), Osped V Cervello, Serv Prevenz & Terapia Talassemia, Unita Ric Piera Cutino, Thalassaemia Ctr, Via Trabuco 180, I-90147 Palermo, Italy. RI Maggio, Aurelio/K-7812-2016 OI Maggio, Aurelio/0000-0002-9601-900X NR 22 TC 13 Z9 14 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0363-0269 J9 HEMOGLOBIN JI Hemoglobin PY 2001 VL 25 IS 1 BP 9 EP 17 DI 10.1081/HEM-100103065 PG 9 WC Biochemistry & Molecular Biology; Hematology SC Biochemistry & Molecular Biology; Hematology GA 455WG UT WOS:000170050300002 PM 11300353 ER PT J AU Chang, KM Thimme, R Melpolder, JJ Oldach, D Pemberton, J Moorhead-Loudis, J McHutchison, JG Alter, HJ Chisari, FV AF Chang, KM Thimme, R Melpolder, JJ Oldach, D Pemberton, J Moorhead-Loudis, J McHutchison, JG Alter, HJ Chisari, FV TI Differential CD4(+) and CD8(+) T-cell responsiveness in hepatitis C virus infection SO HEPATOLOGY LA English DT Article ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; EFFECTOR FUNCTION; VIRAL CLEARANCE; IMMUNE-RESPONSE; TRANSGENIC MICE; QUANTITATIVE-ANALYSIS; SERONEGATIVE DONORS; GAMMA-HERPESVIRUS; TYPE-1 INFECTION; PERIPHERAL-BLOOD AB This study was performed to compare the vigor and phenotype of virus-specific CD4(+) and CD8(+) T-cell responses in patients with different virologic and clinical outcomes after hepatitis C virus (HCV) infection. The results show that a vigorous and multispecific CD4(+) proliferative T-cell response is maintained indefinitely after recovery from HCV infection whereas it is weak and focused in persistently infected patients. In contrast, the HCV-specific CD8(+) T-cell response was quantitatively low in both groups despite the use of sensitive direct ex vivo intracellular interferon gamma (IFN-gamma) staining. Furthermore, although HCV-specific cytolytic CD8(+) memory T cells were undetectable ex vivo, they were readily expanded from the peripheral blood of chronically HCV-infected patients but not from recovered subjects after in vitro stimulation, suggesting that ongoing viremia is required to maintain the HCV-specific memory CD8(+) T-cell response, HCV-specific CD8(+) T cells displayed a type I cytokine profile characterized by production of IFN-gamma despite persistent HCV viremia. The paradoxical observation that HCV-specific CD4(+) T cells survive and CD8(+) T cells are lost after viral clearance while the opposite occurs when HCV persists suggests the existence of differential requirements for the maintenance of CD4(+) and CD8(+) T-cell memory during HCV infection. Furthermore, the relative rarity of circulating CD8(+) effector T cells in chronically infected patients may explain the chronic insidious nature of the liver inflammation and also why they fail to eliminate the virus. C1 Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA USA. Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. Philadelphia Vet Adm Med Ctr, Philadelphia, PA USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. Scripps Clin Med Grp, Div Gastroenterol Hepatol, La Jolla, CA USA. RP Chang, KM (reprint author), Univ Penn, Dept Med, GI Div, A212 Med Res,Univ & Woodland Ave, Philadelphia, PA 19104 USA. RI Chisari, Francis/A-3086-2008 FU NCRR NIH HHS [MO1 RR00833]; NIAID NIH HHS [AI20001, AI47519-01] NR 79 TC 238 Z9 246 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2001 VL 33 IS 1 BP 267 EP 276 DI 10.1053/jhep.2001.21162 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 387BV UT WOS:000166101000033 PM 11124845 ER PT J AU Murray, EA Bussey, TJ AF Murray, EA Bussey, TJ TI Consolidation and the medial temporal lobe revisited: Methodological considerations SO HIPPOCAMPUS LA English DT Article DE hippocampus; perirhinal cortex; nonhuman primates; retrograde memory ID GRADED RETROGRADE-AMNESIA; ENTORHINAL CORTEX; RHESUS-MONKEYS; SPATIAL DISCRIMINATION; ANTEROGRADE AMNESIA; FORNIX TRANSECTION; MEMORY IMPAIRMENT; PARIETAL CORTEX; RHINAL CORTEX; LESIONS AB It is widely believed that new memories are stored in the medial temporal lobe structures in the short term, but then are reorganized over time as the neocortex gradually comes to support stable long-term storage. On this view, the medial temporal lobe structures play a time-limited role in information storage. This putative process of reorganization, known as consolidation, is supported by some clinical findings in humans and by some data from nonhuman animals. Here we review prospective studies of retrograde memory in nonhuman animals, with particular emphasis on experimental design. In considering the evidence for a time-limited role for the medial temporal lobe in information storage, we note that there are alternative interpretations for at least some of the findings typically cited in support of the consolidation process. In addition, we suggest that some studies arguing against the consolidation view should probably be given move weight than they have so far received. Finally, we observe that different structures in the medial temporal lobe are unlikely to operate together as a single functional unit mediating a single consolidation process. Although evidence for a time-limited role for medial temporal lobe structures in memory is at present equivocal, future studies that consider some of the alternative accounts we and others have identified will provide a clearer picture of the mechanisms underlying information storage and retrieval in the brain. Published 2001 Wiley-Liss, Inc.dagger C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Murray, EA (reprint author), NIMH, Neuropsychol Lab, Bldg 49,Room 1B80, Bethesda, MD 20892 USA. RI Bussey, Timothy/M-2758-2016; OI Bussey, Timothy/0000-0001-7518-4041; Murray, Elisabeth/0000-0003-1450-1642 NR 33 TC 29 Z9 30 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 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2001 VL 11 IS 1 BP 1 EP 7 DI 10.1002/1098-1063(2001)11:1<1::AID-HIPO1014>3.0.CO;2-V PG 7 WC Neurosciences SC Neurosciences & Neurology GA 405VE UT WOS:000167180600001 PM 11261768 ER PT J AU Baxter, MG Murray, EA AF Baxter, MG Murray, EA TI Opposite relationship of hippocampal and rhinal cortex damage to delayed nonmatching-to-sample deficits in monkeys SO HIPPOCAMPUS LA English DT Article DE macaque monkey; meta-analysis; hippocampus; recognition memory; perirhinal cortex; visual paired-comparison task ID IMPAIRED RECOGNITION MEMORY; SHORT-TERM-MEMORY; TEMPORAL-LOBE LESIONS; RHESUS-MONKEYS; OBJECT-RECOGNITION; VISUAL RECOGNITION; PERIRHINAL CORTEX; EPISODIC MEMORY; SEMANTIC MEMORY; HUMAN AMNESIA AB Three recent studies in macaque monkeys that examined the effects on memory of restricted hippocampal lesions (Murray and Mishkin, J Neurosci 1 998;1 8:65 68-6582; Beason-Held et al., Hippocampus 1.333;3:562-574; Zola et al., J Neurosci 2000;20:451-463) differed in their conclusions about the involvement of the hippocampus in recognition memory. Because these experiments used a common behavioral procedure, trial-unique visual delayed nonmatching-to-sample (DNMS), a quantitative synthesis ("meta-analysis") was performed to determine whether hippocampal lesions produced a reliable net impairment in DNMS performance, and whether this impairment was related to the magnitude of hippocampal damage. A similar analysis was performed on data from monkeys with perirhinal or rhinal cortex damage (Meunier et al., J Neurosci 1993;13:5418-5432; Buffalo et al., Learn Mem 1999;6:572-599). DNMS performance scores were transformed to d' values to permit comparisons across studies, and a loss in d' score, a measure of the magnitude of the recognition deficit relative to the control group, was calculated for each operated monkey. Two main findings emerged. First, the loss in d' following hippocampal damage was reliably larger than zero, but was smaller than that found after lesions limited to the perirhinal cortex. Second, the correlation of loss in d' with extent of hippocampal damage was large and negative, indicating that greater impairments were associated with smaller hippocampal lesions. This relationship was opposite to that between loss in d' and rhinal cortex damage, for which larger lesions were associated with greater impairment. These findings indicate that damage to the hippocampus and to the rhinal cortex affects recognition memory in different ways. Furthermore, they provide a framework for understanding the seemingly disparate effects of hippocampal damage on recognition memory in monkeys, and by extension, for interpreting the conflicting reports on the effects of such damage on recognition memory abilities in amnesic humans. Published 2001 Wiley-Liss, Inc.dagger C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Baxter, MG (reprint author), Harvard Univ, Dept Psychol, 906 William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. OI Murray, Elisabeth/0000-0003-1450-1642 NR 62 TC 136 Z9 137 U1 1 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2001 VL 11 IS 1 BP 61 EP 71 DI 10.1002/1098-1063(2001)11:1<61::AID-HIPO1021>3.0.CO;2-Z PG 11 WC Neurosciences SC Neurosciences & Neurology GA 405VE UT WOS:000167180600008 PM 11261774 ER PT J AU Baxter, MG Murray, EA AF Baxter, MG Murray, EA TI Effects of hippocampal lesions on delayed nonmatching-to-sample in monkeys: A reply to Zola and Squire (2001) SO HIPPOCAMPUS LA English DT Editorial Material DE macaque monkey; meta-analysis; hippocampus; recognition memory; response ID MEMORY; RECOGNITION C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Baxter, MG (reprint author), Harvard Univ, Dept Psychol, 906 William James Hall,33 Kirkland St, Cambridge, MA 02138 USA. OI Murray, Elisabeth/0000-0003-1450-1642 NR 10 TC 19 Z9 19 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 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2001 VL 11 IS 3 BP 201 EP 203 DI 10.1002/hipo.1037 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 449KU UT WOS:000169684400001 PM 11769304 ER PT J AU Malkova, L Lex, CK Mishkin, M Saunders, RC AF Malkova, L Lex, CK Mishkin, M Saunders, RC TI MRI-based evaluation of locus and extent of neurotoxic lesions in monkeys SO HIPPOCAMPUS LA English DT Article DE ibotenic acid; hippocampal formation; perirhinal cortex; parahippocampal cortex; T2-weighted scan ID EXCITOTOXIC LESIONS; RHESUS-MONKEYS; RHINAL CORTEX; MEMORY; RECOGNITION; AMYGDALA; BRAIN; IMPAIRMENT; DAMAGE AB To minimize the variability in the extent of lesions made by injections of the excitotoxin ibotenic acid in rhesus monkeys, we developed and validated an MRI-based method to determine the efficacy of the injections soon after surgery. T2-weighted MR images were obtained 6-11 days after surgery from 17 brain hemispheres of monkeys that had received bilateral lesions of either the hippocampal formation (HF), perirhinal cortex, or parahippocampal cortex. The extent of lesion estimated from the hypersignal that appeared in and outside of the targeted area on these MR images was compared with the extent of damage assessed histologically after survival periods ranging from 120-370 days. Highly significant correlations (r values between 0.85-0.99) were found between these two measures for several regions in the medial temporal lobe. Based on this finding, lack of hypersignal in the targeted area of some Ss was followed by successful reinjection of the neurotoxin to create more complete cell loss prior to the postoperative phase of the study. We also assessed the relationship between a postoperative reduction in HF volume, measured from T1-weighted MR images, and the extent of damage determined histologically in 14 hemispheres of monkeys with bilateral excitotoxic HF lesions. The HF volume decreases sharply after surgery until 40-50 days postoperatively, after which there is only a minor further decrease. Based on this finding, we obtained T1-weighted MR images at least 44 days but in most cases close to 1 year after surgery. A highly significant positive correlation (r = 0.95, P < 0.001) was found between neuronal damage and volume reduction, with nearly complete neuronal damage (96-99%) corresponding to a volume reduction of 68-79%. These MRI-based methods thus provide an accurate in vivo evaluation of the locus and extent of neurotoxic lesions. Application of these methods can ensure that each animal in the experiment is used effectively. Hippocampus 2001;11:361-370. Published 2001 Wiley-Liss, Inc.. C1 Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Malkova, L (reprint author), Georgetown Univ, Med Ctr, Dept Pharmacol, W217 TRB,3950 Reservoir Rd NW, Washington, DC 20007 USA. NR 16 TC 55 Z9 55 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 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2001 VL 11 IS 4 BP 361 EP 370 DI 10.1002/hipo.1050 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 465QR UT WOS:000170601900003 PM 11530840 ER PT J AU Miyakawa, T Yared, E Pak, JH Huang, FL Huang, KP Crawley, JN AF Miyakawa, T Yared, E Pak, JH Huang, FL Huang, KP Crawley, JN TI Neurogranin null mutant mice display performance deficits on spatial learning tasks with anxiety related components SO HIPPOCAMPUS LA English DT Article DE targeted gene mutation; hippocampus; memory; Morris water maze; Barnes maze ID PROTEIN-KINASE-C; LONG-TERM POTENTIATION; SITE-DIRECTED MUTAGENESIS; NITRIC-OXIDE MODIFICATION; RAT-BRAIN NEUROGRANIN; SYNAPTIC PLASTICITY; MAZE PERFORMANCE; RC3 NEUROGRANIN; MESSENGER-RNA; KNOCKOUT MICE AB Neurogranin/RC3 is a protein that binds calmodulin and serves as a substrate for protein kinase C. Neuronally distributed in the hippocampus and forebrain, neurogranin is highly expressed in dendritic spines of hippocampal pyramidal cells, implicating this protein in longterm potentiation and in learning and memory processes. Null mutation of the neurogranin gene Ng generated viable knockout mice for analysis of the behavioral phenotype resulting from the absence of neurogranin protein. Ng -/- mice were normal on measures of general health, neurological reflexes, sensory abilities, and motor functions, as compared to wild type littermate controls. On the Morris water task, Ng -/- mice failed to reach acquisition criterion on the hidden platform test and did not show selective search on the probe trial. In the Barnes circular maze, another test for spatial navigation learning, Ng -/- mice showed impairments on some components of transfer, but normal performance on time spent around the target hole. Abnormal and idiosyncratic behaviors were detected, that appeared to represent an anxiogenic phenotype in Ng -/- mice, as measured in the light<->dark exploration test and the open field center time parameter. These findings of apparent deficits in spatial learning and anxiety-like tendencies in Ng -/- support a role for neurogranin in the hippocampal ly-mediated interaction between stress and performance. Hippocampus 2001;11:763-775. Published 2001 Wiley-Liss, Inc.(dagger). C1 NIH, Sect Neurobehav Neuropharmacol, Expt Therapeut Branch, Bethesda, MD 20892 USA. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Crawley, JN (reprint author), NIH, Sect Neurobehav Neuropharmacol, Expt Therapeut Branch, Bldg 10,Room 4D11, Bethesda, MD 20892 USA. RI Miyakawa, Tsuyoshi/A-7741-2008 OI Miyakawa, Tsuyoshi/0000-0003-0137-8200 NR 48 TC 98 Z9 110 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 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2001 VL 11 IS 6 BP 763 EP 775 DI 10.1002/hipo.1092 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 506TX UT WOS:000172988800017 PM 11811671 ER PT S AU Beaven, MA Cissel, DS Hundley, TR AF Beaven, MA Cissel, DS Hundley, TR BE Watanabe, T Timmerman, H Yanai, K TI Suppression of MAP kinase pathways in mast cells by glucocorticoids; mechanisms and consequences SO HISTAMINE RESEARCH IN THE NEW MILLENNIUM SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 5th International Histamine Symposium CY NOV 22-25, 2000 CL SENDAI, JAPAN ID FC-EPSILON-RI; NECROSIS-FACTOR-ALPHA; DEXAMETHASONE; ACTIVATION; RECEPTOR; SYK C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Beaven, MA (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50582-2 J9 INT CONGR SER PY 2001 VL 1224 BP 357 EP 362 PG 6 WC Allergy SC Allergy GA BT85D UT WOS:000174224300052 ER PT J AU Khan, S Blackburn, M Mao, DL Huber, R Schlessinger, D Fant, M AF Khan, S Blackburn, M Mao, DL Huber, R Schlessinger, D Fant, M TI Glypican-3 (GPC3) expression in human placenta: localization to the differentiated syncytiotrophoblast SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Article DE placenta; glypican-3; trophoblast; choriocarcinoma ID GOLABI-BEHMEL-SYNDROME; GROWTH-FACTOR-II; HEPARAN-SULFATE PROTEOGLYCANS; ACID-TRANSPORT-SYSTEMS; OVERGROWTH SYNDROMES; FACTOR RECEPTORS; APOPTOSIS; INVITRO; GENE; PROLIFERATION AB The expression of glypican-3 (GPC3), a heparan-sulfate proteoglycan associated with the Simpson-Golabi-Behmel fetal overgrowth syndrome, was studied in normal human placental tissue and cell lines derived from human placentae. Cytotrophoblasts derived from term placentae expressed GPC3 mRNA at low levels in culture. GPC3 mRNA expression increased markedly during trophoblast differentiation. By contrast, fibroblast cell lines derived from normal placentae did not express GPC3 in culture. Similarly, choriocarcinoma cell lines derived from human placentae (BeWo, JAR, and JEG) failed to express GPC3 mRNA. In situ hybridization confirmed the localization of GPC3 mRNA to the syncytiotrophoblast. Furthermore, immunohistochemical staining of paraffin imbedded placental tissue demonstrated intense staining of the syncytiotrophoblast cell layer and less intense staining of cytotrophoblasts. No staining of mesenchymal elements was noted. These data confirm the presence of GPC3 in human placenta and suggest it is expressed by the differentiated syncytiotrophoblast at term. C1 Univ Texas, Houston Med Sch, Dept Pediat, Houston, TX 77030 USA. Univ Texas, Houston Med Sch, Dept Biochem & Mol Biol, Houston, TX USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. NIA, Genet Mol Lab, NIH, Baltimore, MD 21224 USA. RP Fant, M (reprint author), Univ Texas, Houston Med Sch, Dept Pediat, MSB 3-236 6431 Fannin, Houston, TX 77030 USA. OI Blackburn, Michael/0000-0002-1394-9966 FU NICHD NIH HHS [HD20805] NR 31 TC 23 Z9 23 U1 0 U2 1 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD JAN PY 2001 VL 16 IS 1 BP 71 EP 78 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 390TD UT WOS:000166311900009 PM 11193214 ER PT B AU Bubendorf, L Kallioniemi, OP AF Bubendorf, L Kallioniemi, OP BE Li, JJ Li, SA Daling, JR TI Genome scanning and tissue microarrays for the analysis of molecular mechanisms underlying hormone therapy failure in prostate cancer SO HORMONAL CARCINOGENESIS III LA English DT Proceedings Paper CT 3rd International Symposium on Hormonal Carcinogenesis CY SEP 06-12, 1998 CL SEATTLE, WA SP NICHHD, Off Res Womens Hlth, Hoechst Mar Roussel, Seattle Breast Canc Res Program, Fred Hutchinson Canc Res Ctr, NCI, NCI, Div Canc Biol, NCI, Div Canc Control & Populat Sci, Wyeth-Ayerst Res, NIEHS, Int Program, NIEHS ID SOLID TUMORS; IN-VIVO; HYBRIDIZATION; PROGRESSION; GENE C1 NHGRI, Canc Genet Lab, NIH, Bethesda, MD 20892 USA. RP Bubendorf, L (reprint author), NHGRI, Canc Genet Lab, NIH, Bethesda, MD 20892 USA. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 12 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-95127-X PY 2001 BP 103 EP 112 PG 10 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA BR54V UT WOS:000166740700010 ER PT B AU DiAugustine, RP Klotz, DM Richards, RG AF DiAugustine, RP Klotz, DM Richards, RG BE Li, JJ Li, SA Daling, JR TI Introduction - Receptor tyrosine kinases and the effects of ovarian steroids on cell proliferation SO HORMONAL CARCINOGENESIS III LA English DT Proceedings Paper CT 3rd International Symposium on Hormonal Carcinogenesis CY SEP 06-12, 1998 CL SEATTLE, WA SP NICHHD, Off Res Womens Hlth, Hoechst Mar Roussel, Seattle Breast Canc Res Program, Fred Hutchinson Canc Res Ctr, NCI, NCI, Div Canc Biol, NCI, Div Canc Control & Populat Sci, Wyeth-Ayerst Res, NIEHS, Int Program, NIEHS ID EPIDERMAL GROWTH-FACTOR; MOUSE MAMMARY-GLAND; FACTOR-I IGF-1; PHOSPHATIDYLINOSITOL-3 KINASE; DUCTAL MORPHOGENESIS; FACTOR-ALPHA; UTERUS; ESTROGEN; MICE; SUBSTRATE-1 C1 NIEHS, Lab Biochem Risk Assessment, NIH, Res Triangle Pk, NC 27709 USA. RP DiAugustine, RP (reprint author), NIEHS, Lab Biochem Risk Assessment, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-95127-X PY 2001 BP 201 EP 205 PG 5 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA BR54V UT WOS:000166740700020 ER PT B AU Coe, JE Ishak, KG Ross, MJ AF Coe, JE Ishak, KG Ross, MJ BE Li, JJ Li, SA Daling, JR TI Hepatic toxicity of estrogen in Armenian and Chinese hamsters SO HORMONAL CARCINOGENESIS III LA English DT Proceedings Paper CT 3rd International Symposium on Hormonal Carcinogenesis CY SEP 06-12, 1998 CL SEATTLE, WA SP NICHHD, Off Res Womens Hlth, Hoechst Mar Roussel, Seattle Breast Canc Res Program, Fred Hutchinson Canc Res Ctr, NCI, NCI, Div Canc Biol, NCI, Div Canc Control & Populat Sci, Wyeth-Ayerst Res, NIEHS, Int Program, NIEHS ID INDUCTION AB High serum levels of estrogen result in clinically detectable hyperbilirubinemia in two closely related Cricetulus hamsters, the Armenian hamster (Cricetulus migratorius) and the Chinese hamster (Cricetulus griseus). In previous studies, hepatic tumors developed in most Armenian hamsters after chronic estrogen treatment, but in the present study, we found that the livers of Chinese hamsters were remarkably free of neoplastic change under similar conditions. Also, when compared with the responses in the Armenian hamsters, signs of hepatic destruction and regeneration were less prevalent in estrogen-treated Chinese hamsters and the bilirubin levels were lower and of shorter duration. In contrast to the findings in Armenian hamsters, bile canaliculi were severely affected in livers of estrogen-treated Chinese hamsters, and hepatic microvesicular steatosis, indicative of an unusual lipodystrophy caused by estrogen, was prominent. An additional lesion peculiar to the Chinese hamster was a striking sinusoidal dilatation. Although these two hamster species are genetically similar, the genes activated by estrogen receptor show remarkable heterogeneity when their respective livers are examined. Comparisons within these species may provide information about specific gene activation responsible for particular pathologic events. C1 NIAID, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Coe, JE (reprint author), NIAID, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. NR 9 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-95127-X PY 2001 BP 484 EP 488 PG 5 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA BR54V UT WOS:000166740700053 ER PT J AU Schneider, R Bornstein, SR Chrousos, GP Boxberger, S Ehninger, G Breidert, M AF Schneider, R Bornstein, SR Chrousos, GP Boxberger, S Ehninger, G Breidert, M TI Leptin mediates a proliferative response in human gastric mucosa cells with functional receptor SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE leptin; stomach; proliferation; AGS ID GROWTH-FACTORS; OBESE GENE; WEIGHT; MOUSE AB Background: Recently, the rat stomach was reported as a source of leptin, a hormone mainly secreted by adipocytes. Also Helicobacter pylori-induced gastritis in humans was associated with locally elevated leptin levels. In addition, it was suggested that gastric leptin adjusts the function of the intestinal tract in parallel to the function of hypothalamic satiety centers. Aims: Here we examined the synthesis and potential physiologic role of leptin in the human stomach. Methods: RT-PCR was employed to detect leptin mRNA in the human stomach and the human gastric carcinoma cell line AGS while immunogold staining and electron microscopy were used to detect leptin protein. The in vitro effects of leptin on cell proliferation were examined in the ACS cell line. Results: No leptin mRNA could be detected by RT-PCR, yet immunogold labeling and electron microscopy allowed visualization of leptin protein in the human gastric mucosa. At concentrations of 100 nM, leptin led to a significantly increased BrdU-uptake in ACS cells (+ 27%, p < 0.017). The MAP-kinase-1-specific inhibitor U0126 blocked the leptin-induced cell proliferation in a dose-dependent fashion. Conclusions: Leptin protein may not be produced but Father stored in human gastric cells. Leptin-induced increases in the proliferation of gastric mucosa cells suggests that leptin might contribute to mucosal integrity and gastroprotection. C1 Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Med 1, D-01307 Dresden, Germany. Natl Inst Hlth & Human Dev, Dev Endocrinol Branch, NIH, Bethesda, MD USA. RP Breidert, M (reprint author), Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Med 1, Fetscherstr 74, D-01307 Dresden, Germany. NR 24 TC 45 Z9 55 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD JAN PY 2001 VL 33 IS 1 BP 1 EP 6 DI 10.1055/s-2001-12617 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 412KL UT WOS:000167553500001 PM 11280707 ER PT S AU Lakatta, EG AF Lakatta, EG BE Genazzani, AR TI Cardiovascular aging in women and men in the absence of clinical disease SO HORMONE REPLACEMENT THERAPY AND CARDIOVASCULAR DISEASE: THE CURRENT STATUS OF RESEARCH AND PRACTICE SE CONTROVERSIAL ISSUES IN CLIMACTERIC MEDICINE SERIES LA English DT Proceedings Paper CT Workshop on Hormone Replacement Therapy and Cardiovascular Disease CY OCT 13-16, 2000 CL ROYAL SOC MED, LONDON, ENGLAND SP Int Menopause Soc HO ROYAL SOC MED ID AGE-ASSOCIATED CHANGES; UPRIGHT EXERCISE; MYOCARDIAL-ISCHEMIA; ARTERIAL STIFFNESS; SUPINE EXERCISE; HEALTHY-MEN; OLDER MEN; PERFORMANCE; SEX; MECHANISMS C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 33 TC 0 Z9 0 U1 1 U2 2 PU PARTHENON PUBLISHING GROUP LTD PI LANCASTER PA CASTERTON HALL, CARNFORTH, LANCASTER LA6 2LA, ENGLAND SN 1474-3930 BN 1-84214-038-8 J9 CONTRO ISSU CLIM MED PY 2001 BP 7 EP 26 PG 20 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism SC Cardiovascular System & Cardiology; Endocrinology & Metabolism GA BS98G UT WOS:000171592700002 ER PT S AU Hewitt, SC Couse, JF Korach, KS AF Hewitt, SC Couse, JF Korach, KS BE Genazzani, AR TI The estrogen receptor knock-out mouse model SO HORMONE REPLACEMENT THERAPY AND CARDIOVASCULAR DISEASE: THE CURRENT STATUS OF RESEARCH AND PRACTICE SE CONTROVERSIAL ISSUES IN CLIMACTERIC MEDICINE SERIES LA English DT Proceedings Paper CT Workshop on Hormone Replacement Therapy and Cardiovascular Disease CY OCT 13-16, 2000 CL ROYAL SOC MED, LONDON, ENGLAND SP Int Menopause Soc HO ROYAL SOC MED ID TARGETED DISRUPTION; SEXUAL DEVELOPMENT; MICE; GENE; PROGESTERONE; BETA; SUPERFAMILY; PHENOTYPES; CLONING C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Hewitt, SC (reprint author), NIEHS, MD E4 01,111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. NR 26 TC 1 Z9 1 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP LTD PI LANCASTER PA CASTERTON HALL, CARNFORTH, LANCASTER LA6 2LA, ENGLAND SN 1474-3930 BN 1-84214-038-8 J9 CONTRO ISSU CLIM MED PY 2001 BP 81 EP 86 PG 6 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism SC Cardiovascular System & Cardiology; Endocrinology & Metabolism GA BS98G UT WOS:000171592700010 ER PT J AU Charmandari, E Dattani, MT Perry, LA Hindmarsh, PC Brook, CGD AF Charmandari, E Dattani, MT Perry, LA Hindmarsh, PC Brook, CGD TI Kinetics and effect of percutaneous administration of dihydrotestosterone in children SO HORMONE RESEARCH LA English DT Article DE dihydrotestosterone; dihydrotestosterone kinetics; 5 alpha-reductase deficiency; micropenis; hypospadias ID STEROID 5ALPHA-REDUCTASE DEFICIENCY; 5-ALPHA-REDUCTASE DEFICIENCY; MALE PSEUDOHERMAPHRODITISM; PENILE LENGTH; MEN AB Background. Percutaneous administration of dihydrotestosterone (DHT) has been successful in promoting phallic growth in infants and children with 5alpha-reductase deficiency raised as males. We investigated whether percutaneous administration of DHT is similarly effective in patients with micropenis due to alternative diagnoses. Methods: Six patients (age range 1.9-8.3 years) with micropenis of variable etiology were studied prospectively. 2.5% DHT gel was applied to the phallus once daily at a dose of 0.15-0.33 mg/kg body weight. Serum DHT concentrations were measured at 0, 2, 4, 8, 12 and 24 h following application of DHT gel. Results: Peak DHT concentrations were attained within 2-8 h after application of the gel and subsequently remained within the normal adult range in all but 1 patient, who had received the lowest dose of 0.15 mg/kg. An increase in phallic growth, ranging from 0.5-2.0 cm, was achieved after 3-4 months of treatment in all patients whose DHT concentrations were maintained within adult range. Conclusion: Percutaneous administration of DHT in a dose of 0.2-0.3 mg/kg once daily for a period of 3-4 months may be useful in the management of patients with testosterone biosynthetic defects, who have sufficient masculinization to warrant male sex assignment, or in patients with micropenis prior to reconstructive surgery. Copyright (C) 2002 S. Karger AG, Basel. C1 UCL, London Ctr Paediat Endocrinol, London, England. St Bartholomews Hosp, Dept Clin Biochem, London, England. Royal London Hosp, Dept Clin Biochem, London E1 1BB, England. RP Charmandari, E (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Suite 9D42, Bethesda, MD 20892 USA. EM charmane@mail.nih.gov RI Hindmarsh, Peter/C-4964-2008; Charmandari, Evangelia/B-6701-2011; Dattani, Mehul/C-5401-2008 NR 17 TC 13 Z9 16 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PY 2001 VL 56 IS 5-6 BP 177 EP 181 DI 10.1159/000048115 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 536YB UT WOS:000174728500008 PM 11910204 ER PT J AU Dupont, J LeRoith, D AF Dupont, J LeRoith, D TI Insulin and insulin-like growth factor I receptors: Similarities and differences in signal transduction SO HORMONE RESEARCH LA English DT Article; Proceedings Paper CT 5th KIGS/KIMS Expert Meeting on Growth and Growth Disorders CY FEB 02-03, 2001 CL WINDSOR, ENGLAND DE insulin receptor; insulin-like growth factor I; receptor; signalling; specificity; signal transduction ID GLYCOGEN-SYNTHESIS; GENE-EXPRESSION; IGF-1 RECEPTORS; PROTEIN; DOMAIN; FIBROBLASTS; KINASE; PHOSPHORYLATION; ACTIVATION; SUBSTRATE AB The insulin receptor (IR) and the insulin-like growth factor I receptor (IGF-IR) belong to the same subfamily of receptor tyrosine kinases with two extracellular alpha -subunits and two transmembrane beta -subunits. They share a high similarity of structure and intracellular signalling events. However, the IR and the IGF-IR mediate different effects on metabolism, cell proliferation, apoptosis and differentiation. Although some of the variation can be attributed to a different tissue distribution or subcellular localization, it can also be explained by structural differences in the beta -subunit, which may result in activation of specific substrates and signal pathways. Copyright (C) 2001 S. Karger AG, Basel. C1 NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Room 8D12,Bldg 10, Bethesda, MD 20892 USA. NR 27 TC 134 Z9 139 U1 1 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PY 2001 VL 55 SU 2 BP 22 EP 26 DI 10.1159/000063469 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 490TM UT WOS:000172067200005 PM 11684871 ER PT J AU Prochazka, M Walder, K Xia, J AF Prochazka, M Walder, K Xia, J TI AFLP fingerprinting of the human genome SO HUMAN GENETICS LA English DT Article ID DIABETES SUSCEPTIBILITY GENES; PIMA-INDIANS; LINKAGE DISEQUILIBRIUM; WIDE SEARCH; DNA POLYMORPHISMS; COMPLEX TRAITS; MARKERS; LOCI; POPULATIONS; IDENTIFICATION AB Elucidation of the generic basis of complex traits and diseases in humans includes the use of genome-wide association studies that depend on the analysis of a large number of diallelic markers. We describe the application of the amplified fragment length polymorphism (AFLP) technique as an efficient approach for rapidly identifying and scoring multiple variants in the human genome. Using a commercially available kit, we found that AFLP yields reproducible DNA fingerprints consisting of 42-132 fragments, 8% of which show variability between individuals. These variant markers appear to be from different chromosomes, and the majority of them is diallelic. Based on the information obtained in this study, it is possible to approximate the minimum number of selective AFLP primer combinations needed to approach a desired coverage density of all chromosomes. To our knowledge, this is the first study showing the general applicability of AFLP in humans and providing a constructive guide for the design of genomic studies in Homo sapiens with this robust methodology. C1 NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. RP Prochazka, M (reprint author), NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16th St,Rm 5-44, Phoenix, AZ 85016 USA. NR 47 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JAN PY 2001 VL 108 IS 1 BP 59 EP 65 DI 10.1007/s004390000438 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 398DG UT WOS:000166740600009 PM 11214909 ER PT J AU Karas, M Zaks, TZ Yakar, S Dudley, ME LeRoith, D AF Karas, M Zaks, TZ Yakar, S Dudley, ME LeRoith, D TI TCR stimulation protects CD8(+) T cells from CD95 mediated apoptosis SO HUMAN IMMUNOLOGY LA English DT Article DE T cells; TCR activation; CD95; caspase-8; apoptosis ID TUMOR-NECROSIS-FACTOR; FAS-INDUCED APOPTOSIS; METASTATIC MELANOMA; DEATH FACTOR; ACTIVATION; LYMPHOCYTES; LIGAND; INTERLEUKIN-2; INHIBITION; RECEPTORS AB Activation of T cells through the T-cell receptor (TCR) induces the expression of Fas Ligand (CD95L). In turn, CD95L binds to the Fas receptor (CD95) and rapidly induces apoptosis in cycling cells. This interaction is involved in the elimination of reactive lymphocytes during an immune response. However, TCR activation cannot always trigger apoptosis because an effective immune response would then be compromised. Here we show that a short (2 to 3 h) activation of T cells through the TCR simultaneously induces an increase in CD95L mRNA and a dramatic decrease in caspase-8 mRNA levels and proteolytic activity in human CD8(+) T cells. In addition, there is a small reduction in CD95 mRNA and CD95 levels on the cell surface. We found that preactivation of T cells protected them from apoptosis induced by either religation of the TCR or direct exposure to CD95L. These results suggest a mechanism by which cycling CD95-sensitive peripheral T cells, become protected from CD95 mediated deletion when actively engaged in the specific recognition of target cells. Human Immunology 62, 32-38 (2001). (C) American Society for Histocompatibility and Immunogenetics, 2001. Published by Elsevier Science Inc. C1 NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDK, NIH, CEB, Bldg 10,Rm 8D12,10 Ctr Dr,MSC 1758, Bethesda, MD 20892 USA. NR 29 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD JAN PY 2001 VL 62 IS 1 BP 32 EP 38 DI 10.1016/S0198-8859(00)00223-8 PG 7 WC Immunology SC Immunology GA 403HX UT WOS:000167037400004 PM 11165713 ER PT J AU Goudeau, B Dagvadorj, A Rodrigues-Lima, F Nedellec, P Casteras-Simon, M Perret, E Langlois, S Goldfarb, L Vicart, P AF Goudeau, B Dagvadorj, A Rodrigues-Lima, F Nedellec, P Casteras-Simon, M Perret, E Langlois, S Goldfarb, L Vicart, P TI Structural and functional analysis of a new desmin variant causing desmin-related myopathy SO HUMAN MUTATION LA English DT Article DE cardiomyopathy; desmin; DES; desmin-related myopathy; DRM; intermediate filament; sporadic disease ID ALPHA-B-CRYSTALLIN; INTERMEDIATE FILAMENTS; SKELETAL MYOPATHY; MYOFIBRILLAR MYOPATHY; ELECTRON-MICROSCOPY; MISSENSE MUTATION; GENE CAUSES; PROTEINS; SEQUENCE; CELLS AB Desmin-related myopathy is a familial or sporadic disease characterized by skeletal muscle weakness and cardiomyopathy as well as the presence of intracytoplasmic aggregates of desmin-reactive material in the muscle cells. Previously, two kinds of deletions and eight missense mutations have been identified in the desmin gene and proven to be responsible for the disorder. The present study was conducted to determine structural and functional defects in a pathogenic desmin variant that caused a disabling disorder in an isolated case presenting with distal and proximal limb muscle weakness and cardiomyopathy. We identified a novel heterozygous Q389P desmin mutation located at the C-terminal part of the rod domain as the causative mutation in this case. Transfection of desmin cDNA containing the patient's mutation into C2.7, MCF7, and SW13 cells demonstrated that the Q389P mutant is incapable of constructing a functional intermediate filament network and has a dominant negative effect on filament formation. We conclude that Q389P mutation is the molecular event leading to the development of desmin-related myopathy. Hum Mutat 18:388-396, 2001. (C) 2001 Wiley-Liss, Inc. C1 Fac Med, CNRS, UMR 7000, Lab Cytosquelette & Dev, F-75013 Paris, France. Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. NINCDS, Clin Neurogenet Unit, NIH, Bethesda, MD 20892 USA. Inst Pasteur, Serv Microscopie Elect, Dept Retrovirus, Paris, France. RP Vicart, P (reprint author), Fac Med, CNRS, UMR 7000, Lab Cytosquelette & Dev, 105 Bd Hop, F-75013 Paris, France. NR 32 TC 46 Z9 47 U1 1 U2 18 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2001 VL 18 IS 5 BP 388 EP 396 DI 10.1002/humu.1210 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 489WG UT WOS:000172015000004 PM 11668632 ER PT J AU Rogozin, IB Kondrashov, FA Glazko, GV AF Rogozin, IB Kondrashov, FA Glazko, GV TI Use of mutation spectra analysis software SO HUMAN MUTATION LA English DT Review DE classification analysis; software; hotspot; spectra comparison; correlation; repair; replication; mutable motifs; protein structure; mutagen; phenotypic assay; lacI; p53; TP53 ID AMINO-ACID SUBSTITUTIONS; HUMAN HPRT GENE; ESCHERICHIA-COLI; P53 GENE; LACI GENE; SOMATIC HYPERMUTAGENESIS; IMMUNOGLOBULIN GENES; TRANSGENIC ANIMALS; ALKYLATING-AGENTS; DNA AB The study and comparison of mutation(al) spectra is an important problem in molecular biology, because these spectra often reflect on important features of mutations and their fixation. Such features include the interaction of DNA with various mutagens, the function of repair/replication enzymes, and properties of target proteins. It is known that mutability varies significantly along nucleotide sequences, such that mutations often concentrate at certain positions, called "hotspots," in a sequence. In this paper, we discuss in detail two approaches for mutation spectra analysis: the comparison of mutation spectra with a HG-PUBL program, (FTP: sunsite.unc.edu/pub/academic/ biology/dna-mutations/hyperg) and hotspot prediction with the CLUSTERM program (www.itba.mi.cnr.it/webmutation; ftp.bionet.nsc.ru/pub/biology/dbms/clusterm.zip). Several other approaches for mutational spectra analysis, such as the analysis of a target protein structure, hotspot context revealing, multiple spectra comparisons, as well as a number of mutation databases are briefly described. Mutation spectra in the lacl gene of E. coli and the human p53 gene are used for illustration of various difficulties of such analysis. Hum Mutat 17:83-102, 2001. (C) 2001 Wiley-Liss, Inc. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. Penn State Univ, Inst Mol Evolutionary Genet, University Pk, PA 16802 USA. Penn State Univ, Dept Biol, University Pk, PA 16802 USA. RP Rogozin, IB (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike,Bldg 38A,Rm 805, Bethesda, MD 20894 USA. RI Kondrashov, Fyodor Alexeevich/H-6331-2015 OI Kondrashov, Fyodor Alexeevich/0000-0001-8243-4694 FU NIGMS NIH HHS [GM 20293] NR 72 TC 33 Z9 34 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2001 VL 17 IS 2 BP 83 EP 102 DI 10.1002/1098-1004(200102)17:2<83::AID-HUMU1>3.0.CO;2-E PG 20 WC Genetics & Heredity SC Genetics & Heredity GA 398LR UT WOS:000166758400001 PM 11180592 ER PT J AU Nickerson, ML Warren, MB Zbar, B Schmidt, LS AF Nickerson, ML Warren, MB Zbar, B Schmidt, LS TI Random mutagenesis-PCR to introduce alterations into defined DNA sequences for validation of SNP and mutation detection methods SO HUMAN MUTATION LA English DT Article DE mutation detection; single nucleotide polymorphism; SNP; DHPLC; MET proto-oncogene; random mutagenesis; PCR; signature; sequencing ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SINGLE-NUCLEOTIDE POLYMORPHISMS; PAPILLARY RENAL CARCINOMAS; MET PROTOONCOGENE; CONFORMATION POLYMORPHISM; SOMATIC MUTATIONS; DENATURING HPLC; GENE; CANCER; DHPLC AB Sensitive and high throughput techniques are required for the detection of DNA sequence variants such as single nucleotide polymorphisms (SNPs) and mutations. One problem, common to all methods of SNP and mutation detection, is that experimental conditions required for detection of DNA sequence variants depend on the specific DNA sequence to be analyzed. Although algorithms and other calculations have been developed to predict the experimental conditions required to detect DNA sequence variation in a specific DNA sequence, these algorithms do not always provide reliable information and experimental conditions for SNP and mutation detection must be devised empirically. Determination of experimental conditions for detection of DNA sequence variation is difficult when samples containing only wild type sequence are available. When patient derived positive controls are used, increasingly there are valid concerns about commercial ownership and patient privacy. This report presents a rapid and efficient method, employing random mutagenesis-PCR (RM-PCR) using low fidelity DNA polymerase, to randomly introduce single and multiple base substitutions and deletions into DNA sequences of interest. Clones with sequence changes were used to validate denaturing HPLC (DHPLC) algorithm predictions, optimize conditions for mutation detection in exon 15 of the tyrosine kinase domain of the MET proto-oncogene, and to confirm the association between specific DNA sequence changes and unique DHPLC chromatographic profiles (signatures). Finally, DNA from 33 papillary renal carcinoma (PRC) patients was screened for mutations in exon 15 of MET using "validated" DHPLC conditions as a proof of principle application of RM-PCR. Use of RM PCR for DHPLC and other SNP/mutation detection methods is discussed along with challenges associated with detecting sequence alterations in mixed tumor/normal tissue, pooled samples, and from regions of the genome that have been amplified during tumorigenesis or duplicated during evolution. Hum Mutat 17:210-219, 2001. Published 2001 Wiley-Liss, Inc.(dagger). C1 NCI, Immunobiol Lab, 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. RP Nickerson, ML (reprint author), NCI, Immunobiol Lab, Frederick Canc Res & Dev Ctr, Bldg 560,Rm 12-69, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 53 TC 10 Z9 11 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 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2001 VL 17 IS 3 BP 210 EP 219 DI 10.1002/humu.6 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 407EV UT WOS:000167260000006 PM 11241843 ER PT J AU Lipkin, SM Wang, V Stoler, DL Anderson, GR Kirsch, I Hadley, D Lynch, HT Collins, FS AF Lipkin, SM Wang, V Stoler, DL Anderson, GR Kirsch, I Hadley, D Lynch, HT Collins, FS TI Germline and somatic mutation analyses in the DNA mismatch repair gene MLH3: Evidence for somatic mutation in colorectal cancers SO HUMAN MUTATION LA English DT Article DE MLH3; mismatch repair; MMR; colorectal cancer; HNPCC; somatic mutation; microsatellite instability; MSI; SNP; DHPLC; tumorigenesis ID NONPOLYPOSIS COLON-CANCER; II RECEPTOR GENE; MICROSATELLITE INSTABILITY; FRAMESHIFT MUTATIONS; HOMOLOG; TUMORS; MSH6 AB DNA mismatch repair is of considerable scientific and medical importance because of its essential role in maintaining genomic integrity, and its association with hereditary non polyposis colon cancer (HNPCC). Germline mutations in five mismatch repair genes (MLH1, MSH2, PMS1, PMS2, and MSH6) have been associated with HNPCC susceptibility. Our laboratory recently identified MLH3, a novel DNA mismatch repair gene. We screened the MLH3 coding sequence in 60 probands with increased genetic risk factors for colorectal cancer susceptibility and no mutations in the other candidate genes. No definite MLH3 germline mutations were found. We subsequently screened 36 colon tumors, and discovered an appreciable frequency of somatic MLH3 coding mutations in MSI-H tumors (25%). In four of six tumors, evidence of biallelic inactivation was noted. Furthermore, MLH3 nonsense mutations were identified in two of 12 microsatellite stable (MSS) tumors with 14q24 loss of heterozygosity. While our analyses do not exclude the existence of germline MLH3 mutations in patients with increased genetic risk factors for colorectal cancer susceptibility; they suggest such mutations are uncommon in this patient population. The finding of an appreciable frequency of somatic MLH3 mutations is consistent with a possible role for this gene in the progression of colorectal cancer tumorigenesis. Hum Mutat 17:389-396, 2001, Published 2001 Wiley-Liss, Inc. C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Dept Expt Pathol, Buffalo, NY 14263 USA. NCI, Div Genet, Med Branch, Bethesda, MD USA. Creighton Univ, Hereditary Canc Inst, Omaha, NE 68178 USA. Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. RP Collins, FS (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, 9000 Rockville Pike,49-3A14, Bethesda, MD 20892 USA. NR 22 TC 52 Z9 56 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2001 VL 17 IS 5 BP 389 EP 396 DI 10.1002/humu.1114 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 426FH UT WOS:000168338800005 PM 11317354 ER PT J AU Fouts, HN Hewlett, BS Lamb, ME AF Fouts, HN Hewlett, BS Lamb, ME TI Weaning and the nature of early childhood interactions among Bofi foragers in Central Africa SO HUMAN NATURE-AN INTERDISCIPLINARY BIOSOCIAL PERSPECTIVE LA English DT Article DE Central Africa; foragers; weaning; parent-child relations; social and emotional development ID PARENT-OFFSPRING CONFLICT; MATERNAL INVESTMENT; FEEDING PRACTICES; INFANT; PASTORALISTS; NUTRITION; BEHAVIOR AB Western scholarly literature suggests that (1) weaning is initiated by mothers; (2) weaning takes place within a few days once mothers decide to stop nursing (3) mothers employ specific techniques to terminate nursing (4) semi-solid foods (gruels and mashed foods) are essential when weaning; (5) weaning is traumatic for children (it leads to temper tantrums, aggression, etc.); (6) developmental stages in relationships with mothers and others can be demarcated by weaning; and (7) weaning is a process that involves mothers and children exclusively, with weaned children moving from close relationships with their mothers to strengthened relationships with other children. In many respects, these presumptions are consistent with contemporary Euroamerican practices: nursing stops early (usually before six months) relative to other cultures and takes place over a few days or weeks with the help of bottles and baby foods. Because bottles are available, weaning seldom appears traumatic, but it is seen as an important step in the establishment of independence between mothers and infants. By contrast, weaning from the bottle is often perceived as traumatic. Despite considerable academic and popular interest, weaning has seldom been studied systematically, especially in small-scale cultures. Qualitative and quantitative data from a study of Bofi foragers in Central Africa are used here to evaluate the cross-cultural applicability of the assumptions summarized above. C1 Washington State Univ, Dept Anthropol, Pullman, WA 99164 USA. NICHHD, Bethesda, MD 20892 USA. RP Fouts, HN (reprint author), Washington State Univ, Dept Anthropol, Pullman, WA 99164 USA. NR 48 TC 11 Z9 11 U1 1 U2 2 PU ALDINE DE GRUYTER DIVISION WALTER DE GRUYTER INC PI HAWTHORNE PA 200 SAW MILL RIVER, HAWTHORNE, NY 10532 USA SN 1045-6767 J9 HUM NATURE-INT BIOS JI Hum. Nat.-Interdiscip. Biosoc. Perspect. PY 2001 VL 12 IS 1 BP 27 EP 46 DI 10.1007/s12110-001-1012-z PG 20 WC Anthropology; Social Sciences, Biomedical SC Anthropology; Biomedical Social Sciences GA 424FK UT WOS:000168221500003 PM 26191818 ER PT J AU Cai, T Yu, P Tagle, DA Lu, D Chen, YW Xia, JH AF Cai, T Yu, P Tagle, DA Lu, D Chen, YW Xia, JH TI A de novo complex chromosomal rearrangement with a translocation 7;9 and 8q insertion in a male carrier with no infertility SO HUMAN REPRODUCTION LA English DT Article DE carrier; complex chromosomal rearrangement; infertility; male ID 3 GENERATIONS; SEGREGATION; RECOMBINATION; BREAKPOINT; REGION; RISKS AB A de novo complex chromosomal rearrangement (CCR) involving chromosomes 7, 8 and 9 in a male carrier was ascertained through his healthy wife's recurrent spontaneous abortions. Six pregnancies over eight years resulted in four spontaneous abortions and two livebirths who died perinatally due to abnormal vital signs. Cytogenetic analyses utilizing high resolution chromosome banding technique showed a deletion of band in a der(7) chromosome and an extra band inserting at 8q21.2. Another extra band was also observed at the band 9p24, but it could not be karyotypically determined. Fluorescent in-situ hybridization using chromosome 7 and 8 specific microdissected library as probes confirmed the insertion of a segment from the translocated chromosome 7 into a chromosome 8, and additionally revealed a translocation between chromosomes 7 and 9. The karyotype of the CCR carrier was determined as 46,XY,t(7;9)(q22;p24),ins(8;7)(q21.2;q22q32).ish der(9)(wcp7 +);ins(8;7)(wcp8 +,wcp7 +). Comparing with previously reported male CCR carriers with our case, we conclude that male CCR carriers may not always present with infertility or subfertility phenotypes. This may suggest that rare transmission of male carriers could result from abnormal chromosomal rearrangements during meiosis and gametogenesis in addition to frequent infertility. C1 Cent S Univ, Natl Lab Med Genet, Changsha, Peoples R China. NHGRI, Genet & Mol Biol Brnach, NIH, Bethesda, MD 20892 USA. Vet Affairs Med Ctr, Washington, DC 20016 USA. Georgetown Univ, Med Ctr, Washington, DC 20016 USA. RP Cai, T (reprint author), NIDCR, Expt Med Sect, NIH, Bldg 30,Room 112,30 Convent Dr MSC 4322, Bethesda, MD 20892 USA. EM tao.cai@nih.gov NR 22 TC 19 Z9 20 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JAN PY 2001 VL 16 IS 1 BP 59 EP 62 DI 10.1093/humrep/16.1.59 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 393HT UT WOS:000166463700012 PM 11139537 ER PT J AU Grimm, RH Margolis, KL Papademetriou, V Cushman, WC Ford, CE Bettencourt, J Alderman, MH Basile, JN Black, HR DeQuattro, V Eckfeldt, J Hawkins, CM Perry, HM Proschan, M AF Grimm, RH Margolis, KL Papademetriou, V Cushman, WC Ford, CE Bettencourt, J Alderman, MH Basile, JN Black, HR DeQuattro, V Eckfeldt, J Hawkins, CM Perry, HM Proschan, M CA ALLHAT Collaborative Res Grp TI Baseline characteristics of participants in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) SO HYPERTENSION LA English DT Article DE hypertension, essential; antihypertensive agents; diuretics; clinical trials; lipids ID CALCIUM-ANTAGONISTS; RANDOMIZED TRIAL; CARDIOVASCULAR OUTCOMES; SYSTOLIC HYPERTENSION; OLDER PATIENTS; SWEDISH TRIAL; DOUBLE-BLIND; MORBIDITY; MORTALITY; AMLODIPINE AB Diuretics and beta -blockers have been shown to reduce the risk of cardiovascular morbidity and mortality in people with hypertension in long-term clinical trials. No study has compared newer more costly antihypertensive agents (calcium antagonists, ACE inhibitors, and a-adrenergic blockers) with diuretics for reducing the incidence of cardiovascular disease in an ethnically diverse group of middle-aged and elderly hypertensive patients. The study is a randomized, double-blind, active-controlled clinical trial designed to determine whether the incidence of the primary outcome, fatal coronary heart disease or nonfatal myocardial infarction, differs between treatment initiation with a diuretic versus each of 3 other antihypertensive drugs. Men and women aged greater than or equal to 55 years with at least 1 other cardiovascular disease risk factor were randomly assigned to chlorthalidone (12.5 to 25 mg/d), amlodipine (2.5 to 10 mg/d), lisinopril (10 to 40 mg/d), or doxazosin (2 to 8 mg/d) for planned follow-up of 4 to 8 years. This report describes the baseline characteristics of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants. A total of 42 448 participants were randomized from 625 sites in the United States, Canada, Puerto Rico, and the US Virgin Islands. The mean age was 67 years, with 35% aged greater than or equal to 70 years. Among those randomized, 36% were black, 19% were Hispanic, and 47% were women. The sample includes a high proportion of people with diabetes (36%), patients with existing cardiovascular disease (47%), and smokers (22%). There were no important differences between the randomized treatment groups at baseline. ALLHAT will add greatly to our understanding of the management of hypertension by providing an answer to the following question: are newer antihypertensive agents similar, superior, or inferior to traditional treatment with diuretics? C1 Hennepin Cty Med Ctr 865B, Berman Ctr Outcomes & Clin Res, Minneapolis, MN 55415 USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. Memphis Vet Affairs Med Ctr, Memphis, TN USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Vet Affairs Med Ctr, Charleston, SC 29403 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ So Calif, Los Angeles Cty Med Ctr, Los Angeles, CA 90033 USA. White Mem Med Ctr, Los Angeles, CA USA. Univ Minnesota Hosp & Clin, Minneapolis, MN 55455 USA. Vet Affairs Med Ctr, St Louis, MO USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Grimm, RH (reprint author), Hennepin Cty Med Ctr 865B, Berman Ctr Outcomes & Clin Res, 701 Pk Ave S, Minneapolis, MN 55415 USA. OI Papademetriou, Vasilios/0000-0002-2882-2757 NR 28 TC 66 Z9 67 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN PY 2001 VL 37 IS 1 BP 19 EP 27 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 394MM UT WOS:000166527900004 ER PT J AU Wang, HF Ritter, T Cao, WW Shung, KK AF Wang, HF Ritter, T Cao, WW Shung, KK TI High frequency properties of passive materials for ultrasonic transducers SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID MHZ; SPECTROSCOPY; COMPOSITES; WAVES AB The acoustic properties of passive materials for ultrasonic transducers have been measured at room temperature in the frequency range from 25 to 65 MHz using ultrasonic spectroscopy. These materials include alumina/EPO-TEK 301 composites and tungsten/EPO-TEK 301 composites. Experimental results showed that the acoustic impedance of the composites monotonically increased with the volume fraction of the particle filler, which is in agreement with the Denavey model. The attenuation, however, peaked between 7 and 9% volume fraction of particle filler. Far comparison, several other passive materials were also fabricated and measured. The results suggest that materials that possess a higher attenuation also appear to have a larger velocity dispersion. C1 Penn State Univ, Mat Res Lab, University Pk, PA 16802 USA. Penn State Univ, NIH, Resource Ctr Med Ultrason Transducer Technol, University Pk, PA 16802 USA. RP Cao, WW (reprint author), Penn State Univ, Mat Res Lab, University Pk, PA 16802 USA. RI Cao, Wenwu/F-6091-2012 OI Cao, Wenwu/0000-0002-2447-1486 FU NCRR NIH HHS [P41RR11795-01A1] NR 13 TC 74 Z9 76 U1 2 U2 16 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD JAN PY 2001 VL 48 IS 1 BP 78 EP 84 DI 10.1109/58.895911 PG 7 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 391MA UT WOS:000166358700009 PM 11367809 ER PT S AU Horwitz, B Husain, FT Braun, AR Tagamets, MA AF Horwitz, B Husain, FT Braun, AR Tagamets, MA GP IEEE IEEE IEEE IEEE TI Simulating PET/fMRI studies of visual and auditory pattern recognition using biologically realistic large-scale neural models SO IJCNN'01: INTERNATIONAL JOINT CONFERENCE ON NEURAL NETWORKS, VOLS 1-4, PROCEEDINGS SE IEEE International Joint Conference on Neural Networks (IJCNN) LA English DT Proceedings Paper CT International Joint Conference on Neural Networks (IJCNN 01) CY JUL 15-19, 2001 CL WASHINGTON, D.C. SP Int Neural Network Soc, IEEE, Neural Networks Council ID BLIND SEPARATION; FUNCTIONAL MRI; HUMAN BRAIN; DATA SETS; FMRI; PET; COMPONENTS AB Formidable conceptual problems exist in interpreting human functional neuroimaging data in terms of the underlying neural activity. To surmount these difficulties, we have developed two neurobiologically realistic models (one for vision, one for audition) of the object recognition pathway in human neocortex in which data at multiple spatiotemporal levels can be simulated and cross-validated by multiple disciplines, including PET and fMRI. Our models, based on neurophysiological and neuroanatomical data from primate and human studies, enable us to simultaneously simulate cellular electrophysiological and PET/fMRI activities in multiple, interconnected brain regions. These types of models enable us to quantitatively combine multiple data sets so that a coherent account Of human cognition can be generated. We illustrate this approach using delayed match-to-sample (DMS) tasks for visual shape and for auditory tonal patterns. C1 Natl Inst Deafness & Other Commun Disorders, Language Sect, NIH, Bethesda, MD 20892 USA. RP Horwitz, B (reprint author), Natl Inst Deafness & Other Commun Disorders, Language Sect, NIH, Bethesda, MD 20892 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1098-7576 BN 0-7803-7044-9 J9 IEEE IJCNN PY 2001 BP 878 EP 883 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Theory & Methods SC Computer Science GA BT36Q UT WOS:000172784800157 ER PT S AU DeLeo, JM Rosenfeld, S AF DeLeo, JM Rosenfeld, S GP IEEE IEEE IEEE IEEE TI Essential roles for receiver operating characteristic (ROC) methodology in classifier neural network applications SO IJCNN'01: INTERNATIONAL JOINT CONFERENCE ON NEURAL NETWORKS, VOLS 1-4, PROCEEDINGS SE IEEE International Joint Conference on Neural Networks (IJCNN) LA English DT Proceedings Paper CT International Joint Conference on Neural Networks (IJCNN 01) CY JUL 15-19, 2001 CL WASHINGTON, D.C. SP Int Neural Network Soc, IEEE, Neural Networks Council ID DECISION-MAKING C1 NIH, Dept Clin Res Informat, Ctr Clin, Bethesda, MD 20892 USA. RP DeLeo, JM (reprint author), NIH, Dept Clin Res Informat, Ctr Clin, Bethesda, MD 20892 USA. NR 15 TC 1 Z9 1 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1098-7576 BN 0-7803-7044-9 J9 IEEE IJCNN PY 2001 BP 2730 EP 2731 DI 10.1109/IJCNN.2001.938804 PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Theory & Methods SC Computer Science GA BT36Q UT WOS:000172784800486 ER PT S AU DeLeo, JM Dayhoff, JE AF DeLeo, JM Dayhoff, JE GP IEEE IEEE IEEE IEEE TI Medical applications of neural networks: Measures of certainty and statistical tradeoffs SO IJCNN'01: INTERNATIONAL JOINT CONFERENCE ON NEURAL NETWORKS, VOLS 1-4, PROCEEDINGS SE IEEE International Joint Conference on Neural Networks (IJCNN) LA English DT Proceedings Paper CT International Joint Conference on Neural Networks (IJCNN 01) CY JUL 15-19, 2001 CL WASHINGTON, D.C. SP Int Neural Network Soc, IEEE, Neural Networks Council ID DECISION-MAKING; PLOTS AB Artificial neural networks are well-established as viable, multi-purpose, robust computational methodologies with solid theoretical support and with strong potential to be effective in medicine once issues of certainty and statistical tradeoffs are further addressed. Here, we view the output of a classification neural network as a composite variable that can be subjected to the same kind of statistical analysis as any other clinical variable used in classification decisions. We show that ROC methodology, long used in medicine, can be used in neural network performance evaluation and in sharpening final decisions by, adjusting outputs for prevalence and misclassification costs. We explore the use of ensembles of neural networks to estimate classification confidence intervals. Since it is possible to predict outcomes for individual patients with neural networks, we suggest a paradigm shift from previous "bin-model" approaches, in which patient outcome and management decisions are assumed from wide statistical groups into which the patient fits, to decisions customized to the individual patient. C1 NIH, Dept Clin Res Informat, Ctr Clin, Bethesda, MD 20892 USA. RP DeLeo, JM (reprint author), NIH, Dept Clin Res Informat, Ctr Clin, Bethesda, MD 20892 USA. NR 17 TC 3 Z9 3 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1098-7576 BN 0-7803-7044-9 J9 IEEE IJCNN PY 2001 BP 3009 EP 3014 DI 10.1109/IJCNN.2001.938857 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Theory & Methods SC Computer Science GA BT36Q UT WOS:000172784800537 ER PT J AU Hu-Li, J Pannetier, C Guo, LY Lohning, M Gu, H Watson, C Assenmacher, M Radbruch, A Paul, WE AF Hu-Li, J Pannetier, C Guo, LY Lohning, M Gu, H Watson, C Assenmacher, M Radbruch, A Paul, WE TI Regulation of expression of IL-4 alleles: Analysis using a chimeric GFP/IL-4 gene SO IMMUNITY LA English DT Article ID GERMINAL-CENTER FORMATION; T-CELL DIFFERENTIATION; CYTOKINE EXPRESSION; RECEPTOR; TH1; INACTIVATION; INFLAMMATION; ACTIVATION; EXCLUSION; MECHANISM AB CD4 cells from mice heterozygous for an IL-4 and a GFP/IL-4 gene frequently express a single allele. Analysis of IL-4 or GFP production by cells from recently primed Th2 cells indicates that essentially all are competent to transcribe either allele but have a low probability of doing so. By contrast, long-term Th2 clones show distinct and heritable ratios in the proportion of cells that express IL-4 or GFP. We conclude that in the course of Th2 priming an early efficient event renders both alleles capable of being inefficiently transcribed; a second, less frequent event occurs that renders one allele more competent, accounting for the differential expression of IL-4 and GFP in different clones. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Deutsch Rheumaforschungszentrum, D-10117 Berlin, Germany. Miltenyi Biotec, D-51429 Bergisch Gladbach, Germany. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 33 TC 101 Z9 102 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 2001 VL 14 IS 1 BP 1 EP 11 DI 10.1016/S1074-7613(01)00084-X PG 11 WC Immunology SC Immunology GA 394FQ UT WOS:000166513800001 PM 11163225 ER PT J AU Dykstra, ML Longnecker, R Pierce, SK AF Dykstra, ML Longnecker, R Pierce, SK TI Epstein-Barr virus coopts lipid rafts to block the signaling and antigen transport functions of the BCR SO IMMUNITY LA English DT Article ID MEMBRANE-PROTEIN 2A; MEMORY B-CELLS; IN-VIVO; T-CELL; REGULATES REACTIVATION; LYMPHOCYTE ACTIVATION; CYTOPLASMIC DOMAINS; PERIPHERAL-BLOOD; TYROSINE KINASES; CROSS-LINKING AB The B cell antigen receptor (BCR) functions to initiate signaling and to internalize antigen for processing from within Lyn kinase-enriched membrane lipid rafts. The signaling function of the BCR is blocked by Epstein-Barr Virus (EBV] latent membrane protein 2A (LMP2A), which is constitutively phosphorylated by Lyn. Here, we show that LMP2A resides in lipid rafts and excludes the BCR from entering rafts by Lyn-dependent mechanisms, thus blocking both BCR signaling and antigen transport. Mutant LMP2A that permits BCR signaling and raft translocation still blocks antigen trafficking, indicating independent control of these BCR functions. Thus, EBV coopts the lipid rafts to disarm both the signaling and antigen-processing functions of the BCR by independent mechanisms. C1 Northwestern Univ, Sch Med, Dept Immunol Microbiol, Chicago, IL 60611 USA. RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. FU NCI NIH HHS [CA62234, CA73507]; NIGMS NIH HHS [T32 GM08061, T32 GM008061] NR 50 TC 115 Z9 122 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 2001 VL 14 IS 1 BP 57 EP 67 DI 10.1016/S1074-7613(01)00089-9 PG 11 WC Immunology SC Immunology GA 394FQ UT WOS:000166513800006 PM 11163230 ER PT J AU Li, YL Li, HM Dimasi, N McCormick, JK Martin, R Schuck, P Schlievert, PM Mariuzza, RA AF Li, YL Li, HM Dimasi, N McCormick, JK Martin, R Schuck, P Schlievert, PM Mariuzza, RA TI Crystal structure of a superantigen bound to the high-affinity, zinc-dependent site on MHC class II SO IMMUNITY LA English DT Article ID STAPHYLOCOCCAL-ENTEROTOXIN-A; COMPLEX CLASS-II; TOXIC SHOCK SYNDROME; BINDING-SITES; STREPTOCOCCUS-PYOGENES; MULTIPLE-SCLEROSIS; HLA-DR; PEPTIDE; APOPTOSIS; MOLECULE AB MHC class II molecules possess two binding sites for bacterial superantigens (SAGs): a low-affinity site on the cu chain and a high-affinity, zinc-dependent site on the beta chain. only the former has been defined crystallographically. We report the structure of streptococcal pyrogenic exotoxin C (SPE-C) complexed with HLA-DR2a (DRA*010l, DRB5*0101) bearing a self-peptide from myelin basic protein (MBP). SPE-C binds the beta chain through a zinc bridge that links the SAG and class II molecules. Surprisingly, SPE-C also makes extensive contacts with the MBP peptide, such that peptide accounts for one third of the surface area of the MHC molecule buried in the complex, similar to TCR-peptide/MHC complexes. Thus, SPE-C may optimize T cell responses by mimicking the peptide dependence of conventional antigen presentation and recognition. C1 Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. RP Mariuzza, RA (reprint author), Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. RI McCormick, John/E-4232-2015; OI Li, Hongmin/0000-0002-8684-5308; Schuck, Peter/0000-0002-8859-6966 FU NIAID NIH HHS [AI42937, AI36900]; PHS HHS [36611] NR 48 TC 89 Z9 95 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 2001 VL 14 IS 1 BP 93 EP 103 DI 10.1016/S1074-7613(01)00092-9 PG 11 WC Immunology SC Immunology GA 394FQ UT WOS:000166513800009 PM 11163233 ER PT S AU Cohen, JI AF Cohen, JI BE Gershon, AA Calisher, CH Arvin, AM TI Mutagenesis of the varicella-zoster virus genome: lessons learned SO IMMUNITY TO AND PREVENTION OF HERPES ZOSTER SE ARCHIVES OF VIROLOGY, SUPPLEMENTUM LA English DT Proceedings Paper CT International Conference on Immunity and Prevention of Herpes Zoster CY MAR 08-10, 1999 CL OSAKA, JAPAN ID HERPES-SIMPLEX VIRUS; PUTATIVE PROTEIN-KINASES; READING FRAME-10 PROTEIN; SCID-HU MOUSE; GENE PROMOTERS; VIRAL MUTANTS; IN-VITRO; VZV; REPLICATION; TYPE-1 AB The varicella-zoster virus (VZV) genome encodes at least 70 genes. We have developed a cosmid based system to inactivate individual viral genes or to insert foreign genes into the genome. We have shown that many VZV genes are not required for replication of the virus in cell culture. Several of these genes, including VZV ORF61, ORF47, and ORF10, have unexpected phenotypes in cell culture and differ from their homologs in the better studied herpes simplex virus (HSV). We have also used the Oka strain of VZV as a live virus vaccine vector. Guinea pigs vaccinated with recombinant VZV expressing HSV-2 glycoprotein D and challenged with HSV-2 have reduced severity of primary genital herpes and reduced mortality compared to animals receiving parental VZV. Recently we have inserted the human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) glycoprotein 160 genes into the Oka strain of VZV and have shown that these proteins are expressed in recombinant virus-infected cells. Thus, directed mutagenesis of the VZV genome is providing new insights into viral pathogenesis and may provide new candidate vaccines. C1 NIH, Med Virol Sect, Clin Invest Lab, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIH, Med Virol Sect, Clin Invest Lab, Bethesda, MD 20892 USA. NR 29 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0939-1983 BN 3-211-83555-5 J9 ARCH VIR S PY 2001 VL 17 BP 91 EP 97 PG 7 WC Public, Environmental & Occupational Health; Immunology; Virology SC Public, Environmental & Occupational Health; Immunology; Virology GA BS22Q UT WOS:000169113800010 ER PT S AU Straus, SE AF Straus, SE BE Gershon, AA Calisher, CH Arvin, AM TI Varicella-zoster virus immunity and prevention: a conference perspective SO IMMUNITY TO AND PREVENTION OF HERPES ZOSTER SE ARCHIVES OF VIROLOGY, SUPPLEMENTUM LA English DT Proceedings Paper CT International Conference on Immunity and Prevention of Herpes Zoster CY MAR 08-10, 1999 CL OSAKA, JAPAN ID BONE-MARROW TRANSPLANTATION; TRIGEMINAL GANGLIA; INFECTION; VACCINE; PATIENT AB This report offers a concise overview of the VZV Conference, highlighting recent developments in the field and speculating on areas of greatest opportunity and need for future work. The goal of eradicating VZV disease will be facilitated by a multifaceted research agenda directed at a fuller comprehension of how the virus replicates, spreads and persists, and how it eludes host immune responses. C1 NIH, NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. RP Straus, SE (reprint author), NIH, NIAID, Clin Invest Lab, 10 Ctr Dr,Room 10-11N228, Bethesda, MD 20892 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0939-1983 BN 3-211-83555-5 J9 ARCH VIR S PY 2001 VL 17 BP 173 EP 178 PG 6 WC Public, Environmental & Occupational Health; Immunology; Virology SC Public, Environmental & Occupational Health; Immunology; Virology GA BS22Q UT WOS:000169113800018 ER PT J AU Stillwell, R Bierer, BE AF Stillwell, R Bierer, BE TI T cell signal transduction and the role of CD7 in costimulation SO IMMUNOLOGIC RESEARCH LA English DT Review DE T cell receptor; CD3; CD7; CD28; coreceptor; costimulation; lymphocycte signal transduction ID TYROSINE-PROTEIN-KINASE; AMINO-TERMINAL DOMAIN; CROSS-LINKING CD7; PHOSPHATIDYLINOSITOL 3-KINASE; ANTIGEN RECEPTOR; PHOSPHOINOSITIDE 3-KINASE; MONOCLONAL-ANTIBODY; LYMPHOCYTE-ACTIVATION; MEMBRANE MICRODOMAINS; CYTOPLASMIC DOMAINS AB The complex cellular interactions that govern the mammalian immune response are now known to include specific receptor/ligand interactions, recruitment of intracellular signaling molecules, activation of both kinases and phosphatases, and redistribution of macromolecular complexes into specific subcellular membrane locations that, in aggregate, result in transcriptional activation. While the TCR-CD3 signal is critical for activation of the resting T cell, it alone is not sufficient to initiate transcriptional activation or generate an effective immune response. A number of other coreceptor molecules, including CD4, CD8, and CD28, have now been characterized that also play important roles in initiating or amplifying the activation of the T cell. A 40 kDa member of the immunoglobulin superfamily, the CD7 molecule, has also been shown to have costimulatory activity and to induce tyrosine and lipid kinase activities. Here we will review the signaling pathways initiated by TCR, CD28, and CD7, as well as the functional consequences of signal transduction through these receptors. C1 NHLBI, Lab Lymphocyte Biol, Lab Res program, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Bierer, BE (reprint author), NHLBI, Lab Lymphocyte Biol, Lab Res program, Div Intramural Res,NIH, 10 Ctr Dr,10-6C208, Bethesda, MD 20892 USA. NR 185 TC 29 Z9 29 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2001 VL 24 IS 1 BP 31 EP 52 DI 10.1385/IR:24:1:31 PG 22 WC Immunology SC Immunology GA 450VK UT WOS:000169765400003 PM 11485208 ER PT J AU Diaw, L Siwarski, D Huppi, K AF Diaw, L Siwarski, D Huppi, K TI Double light chain producing lymphocytes - An enigma of allelic exclusion SO IMMUNOLOGIC RESEARCH LA English DT Article DE B lymphocyte; double light chain; allelic exclusion; kappa; lambda ID IMMUNOGLOBULIN KAPPA-LIGHT; B-CELLS; GENE REARRANGEMENT; ANTIGEN RECEPTORS; SURFACE EXPRESSION; T-CELLS; LYMPHOMA AB The infrequent double light chain producing lymphocyte (DLCPL) is discussed in the context of allelic exclusion. Principally allelic selection rather than allelic exclusion would suggest a role for the DLCPL in the normal B cell population rather than as an aberrance of B cell malignancy. Found primarily in the periphery, it is uncertain at what stage of B cell ontogeny the DLCPL might reside. Nevertheless, through the possible presentation of two functional surface receptors, the DLCPL could be capable of recognizing both self and nonself epitopes. C1 NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Huppi, K (reprint author), NCI, Genet Lab, NIH, Bldg 37,Room 2B-21, Bethesda, MD 20892 USA. NR 51 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2001 VL 24 IS 3 BP 303 EP 310 DI 10.1385/IR:24:3:303 PG 8 WC Immunology SC Immunology GA 494RQ UT WOS:000172300000005 PM 11817327 ER PT J AU Bhattacharyya, SP AF Bhattacharyya, SP TI Ubiquitination of Lyn-kinase in rat basophilic leukemia RBL-2H3 cells SO IMMUNOLOGY LETTERS LA English DT Article DE Lyn RBL-2H3 cells; ubiquitination ID PROTEIN-DEGRADATION; TYROSINE KINASES; SYSTEM; RECEPTOR; IGE AB Receptor-mediated signal transduction pathways of cells involved in allergy and inflammations are extremely significant. Lyn is a member of the Src family of non-receptor protein tyrosine kinases and is associated with a number of cell surface receptors, including the B-cell antigen receptor and immunoglobulin E receptor (Fc epsilon RI). Lyn is necessary for Fc epsilon RI-mediated mast cell activation. To investigate how the level of Lyn is maintained in mast cell activation, it was studied whether Lyn binds to ubiquitin and is ubiquitinated for proteasomal degradation in cells. In the yeast two hybrid system, Lyn specifically interacted with ubiquitin in vivo. Furthermore, Lyn bound to ubiquitin-conjugated Sepharose beads in vitro and was efficiently competed by soluble ubiquitin. Pulse-chase experiments indicated intracellular degradation of Lyn was associated with the generation of a high molecular weight complex in the presence of proteasome-specific inhibitor, lactacystin. This high molecular weight complex cross-reacted with anti-Lyn and anti-ubiquitin demonstrating the ubiquitination Lyn. Overexpression of Lyn and ubiquitin in COS 7.2 cells also resulted in the ubiquitination of Lyn in the presence of lactacystin, supporting the ubiquitination of Lyn by proteasome specific pathway. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Bhattacharyya, SP (reprint author), NIAID, Lab Allerg Dis, NIH, NIH Campus,Bldg 29,Room 304,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 19 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD JAN 1 PY 2001 VL 75 IS 2 BP 131 EP 136 DI 10.1016/S0165-2478(00)00289-3 PG 6 WC Immunology SC Immunology GA 388YT UT WOS:000166211200008 PM 11137137 ER PT J AU Jeong, HJ Koo, HN Myung, NI Shin, MK Kim, JW Kim, DK Kim, KS Kim, HM Lee, YM AF Jeong, HJ Koo, HN Myung, NI Shin, MK Kim, JW Kim, DK Kim, KS Kim, HM Lee, YM TI Inhibitory effects of mast cell-mediated allergic reactions by cell cultured Siberian Ginseng SO IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY LA English DT Article ID ACANTHOPANAX-SENTICOSUS; MESSENGER-RNA; HIGH-AFFINITY; IGE; ACTIVATION; RECEPTOR; RATS; ANAPHYLAXIS; SKIN AB The crude drug "Siberian Ginseng (SG)" has long been used in empirical Oriental medicine for the nonspecific enhancement of resistance in humans and animals. In this study, we investigated the effect of cell cultured SG by oral administration in mast cell-mediated allergic reactions. SG dose-dependently inhibited compound 48/80-induced systemic allergy with doses of 10(-2) to 1 g/kg 1 h before oral administration. Of special note, SG inhibited systemic allergy with the dose of I g/kg by 25%. SG (1 g/kg) also inhibited passive cutaneous allergic reaction by 51%. SG dose-dependently inhibited histamine release from rat peritoneal mast cells. When SG (0.01 mg/ml) was added, the secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 in antidinitrophenyl (DNP) IgE antibody-stimulated mast cells was inhibited 39.5% and 23.3%, respectively. In addition, SG inhibited anti-DNP IgE antibody-stimulated TNF-alpha protein expression in mast cells. Our studies provide evidence that SG may be beneficial in the treatment of various types of allergic diseases. C1 Wonkwang Univ, Coll Pharm, Dept Oriental Pharm, Iksan 570749, Chonbuk, South Korea. Wonkwang Univ, Ctr Oriental Med Sci, Iksan 570749, Chonbuk, South Korea. Wonkwang Univ, Dept Herbal, Coll Oriental Med, Iksan 570749, Chonbuk, South Korea. Microplants Co Ltd, Cell Culture Res Unit, Tukjin Gu, Chonju 561232, Chonbuk, South Korea. NIAID, Lab Allerg Div, NIH, Rockville, MD 20852 USA. Chonbuk Natl Univ, Coll Nat Sci, Div Biol Sci, Chonju 561756, Chonbuk, South Korea. RP Lee, YM (reprint author), Wonkwang Univ, Coll Pharm, Dept Oriental Pharm, Iksan 570749, Chonbuk, South Korea. NR 20 TC 20 Z9 20 U1 1 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0892-3973 J9 IMMUNOPHARM IMMUNOT JI Immunopharmacol. Immunotoxicol. PY 2001 VL 23 IS 1 BP 107 EP 117 DI 10.1081/IPH-100102572 PG 11 WC Immunology; Pharmacology & Pharmacy; Toxicology SC Immunology; Pharmacology & Pharmacy; Toxicology GA 455WB UT WOS:000170049800011 PM 11322643 ER PT J AU Alvarado-Ramy, F Alter, MJ Bower, W Henderson, DK Sohn, AH Sinkowitz-Cochran, RL Jarvis, WR AF Alvarado-Ramy, F Alter, MJ Bower, W Henderson, DK Sohn, AH Sinkowitz-Cochran, RL Jarvis, WR TI Management of occupational exposures to hepatitis C virus: Current practice and controversies SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article AB Unlike hepatitis B virus and human immunodeficiency virus, there currently are no immunization or chemoprophylactic interventions available to prevent infection after an occupational exposure to hepatitis C virus (HCV). A "Reality Check" session was held at the 4th Decennial International Conference on Nosocomial and Healthcare-Associated Infections to gather information on current practices related to management of occupational exposures to HCV, generate discussion on controversial issues, and identify areas for future research. Infection control professionals in attendance were knowledgeable in most issues addressed regarding the management of occupational exposures to HCV. Areas of controversy included the use of antiviral therapy early in the course of HCV infection and the appropriate administrative management of an HCV-infected healthcare worker (Infect Control Hosp Epidemiol 2001;22:53-55). C1 US Dept HHS, Hosp Infect Program, Natl Ctr Infect Dis, Ctr Dis Control & Prevent,Publ Hlth Serv, Atlanta, GA 30333 USA. US Dept HHS, Epidem Intelligence Serv, Div Appl Publ Hlth Training,Epidemiol Program Off, Ctr Dis Control & Prevent,Publ Hlth Serv, Atlanta, GA 30333 USA. CDC, Div Viral & Rickettsial Dis, Atlanta, GA 30333 USA. NIH, Warren G Magnuson Clin Ctr, Off Director, Bethesda, MD 20892 USA. RP Alvarado-Ramy, F (reprint author), US Dept HHS, Hosp Infect Program, Natl Ctr Infect Dis, Ctr Dis Control & Prevent,Publ Hlth Serv, 1600 Clifton Rd,Mail Stop E-68, Atlanta, GA 30333 USA. NR 4 TC 7 Z9 8 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JAN PY 2001 VL 22 IS 1 BP 53 EP 55 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 392YF UT WOS:000166439600013 PM 11198026 ER PT J AU Cunningham, ML Price, HC O'Connor, RW Moorman, MP Mahler, JF Nold, JB Morgan, DL AF Cunningham, ML Price, HC O'Connor, RW Moorman, MP Mahler, JF Nold, JB Morgan, DL TI Inhalation toxicity studies of the alpha,beta-unsaturated ketones: 2-cyclohexene-1-one SO INHALATION TOXICOLOGY LA English DT Article ID MUTAGENICITY; SMOKE AB 2-Cyclohexene-1-one (CHX) is a cyclic alpha,beta -unsaturated ketone with broad human exposure. CHX is an environmental pollutant and is present in tobacco smoke and in soft drinks sweetened with cyclamate. Interest in the toxicity of this class of compounds is due to their structural similarity to the cytotoxin acrolein. In a pilot study, rats and mice were exposed to 0, 20, 40, or 80 ppm CHX for 6 h/day. The study was terminated after 4 days due to acute toxicity in the high-dose groups. In a subsequent 14-day study, mice and rats were exposed to 0, 2.5, 5, or 10 ppm CHX for 6 h/day. All animals survived exposure until terminal sacrifice. Body weights were not significantly different from controls after 14 days of exposure. Liver/body weights were increased in male and female mice exposed to 5 and 10 ppm, and in male and female rats exposed to 10 ppm CHX. Ninety-day toxicity studies were conducted to provide data required to design chronic toxicity and carcinogenicity studies of CHX if it is determined such studies are necessary. Groups of 10 male and female F-344 rats and B6C3F1 mice were exposed to 0, 2.5, 5, or 10 ppm CHX for 6 h/day for 13 wk. All animals survived until sacrifice. Body weights were not significantly different from controls after 13 wk of exposure. Liver weights were increased in male and female mice exposed to 5 and 10 ppm and in male and female rats exposed to 10 ppm CHX. No adverse effects on bone-marrow micronuclei, sperm motility, or vaginal cytology were observed. Microscopic lesions included hyperplasia, and squamous metaplasia in the nasal cavity in rats and mice or both sexes at all doses. Nasal-cavity erosion and suppurative inflammation also occurred in high-dose mice. Larynx and lung were not affected in either sex or species. Dose-related hepatic centrilobular cytoplasmic vacuolation was seen in male rats only. These data suggest that CHX acts as an alkylating agent primarily producing toxicity at the exposure site. C1 NIEHS, Lab Pharmacol & Chem, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. ManTech Environm Toxicol Inc, Res Triangle Pk, NC USA. Pathol Associates Int, Res Triangle Pk, NC USA. RP Cunningham, ML (reprint author), NIEHS, Lab Pharmacol & Chem, Natl Toxicol Program, NIH, Mail Drop B3-10, Res Triangle Pk, NC 27709 USA. NR 14 TC 9 Z9 9 U1 3 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD JAN PY 2001 VL 13 IS 1 BP 25 EP 36 PG 12 WC Toxicology SC Toxicology GA 392EM UT WOS:000166398000002 PM 11153058 ER PT J AU Simon-Nobbe, B Kodzius, R Kajava, A Ferreira, F Kungl, A Achatz, G Crameri, R Ebner, C Breitenbach, M AF Simon-Nobbe, B Kodzius, R Kajava, A Ferreira, F Kungl, A Achatz, G Crameri, R Ebner, C Breitenbach, M TI Structure of an IgE-binding peptide from fungal enolases SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 23rd Symposium of the Collegium Internationale Allergologicum (CIA 2000) CY MAY 18-23, 2000 CL HAKONE, JAPAN DE Cladosporium herbarum; Alternaria alternata; allergen; enolase; epitope; cross-reactivity; phage display; Aspergillus fumigatus; Candida albicans; Saccharomyces cerevisiae ID ALTERNARIA-ALTERNATA; CELL-WALL; PROTEINS; EXPRESSION; ALLERGENS; CLONING C1 Salzburg Univ, Inst Genet & Gen Biol, A-5020 Salzburg, Austria. Graz Univ, Dept Pharmaceut Chem, Graz, Austria. Univ Vienna, Dept Pathophysiol, Vienna, Austria. Swiss Inst Allergy & Asthma Res, SIAF, CH-7270 Davos, Switzerland. NIH, CIT, Ctr Mol Modeling, Bethesda, MD 20892 USA. RP Breitenbach, M (reprint author), Salzburg Univ, Inst Genet & Gen Biol, Hellbrunnerstr 34, A-5020 Salzburg, Austria. RI Achatz, Gernot/E-5073-2011; Kajava, Andrey/E-1107-2014; OI Kajava, Andrey/0000-0002-2342-6886; Kodzius, Rimantas/0000-0001-9417-8894 NR 8 TC 1 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD JAN-MAR PY 2001 VL 124 IS 1-3 BP 93 EP 94 DI 10.1159/000053679 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 422MU UT WOS:000168123200024 ER PT J AU Rivera, J Arudchandran, R Gonzalez-Espinosa, C Manetz, TS Xirasagar, S AF Rivera, J Arudchandran, R Gonzalez-Espinosa, C Manetz, TS Xirasagar, S TI A perspective: Regulation of IgE receptor-mediated mast cell responses by a LAT-organized plasma membrane-localized signaling complex SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 23rd Symposium of the Collegium Internationale Allergologicum (CIA 2000) CY MAY 18-23, 2000 CL HAKONE, JAPAN DE mast cells; Fc epsilon RI; LAT; Vav; signal transduction; exocytosis; cytokines ID T-CELL; TYROSINE PHOSPHORYLATION; IMMUNOGLOBULIN-E; ACTIVATION; VAV; TRANSDUCTION; AGGREGATION; MECHANISM; KINASES; DOMAIN AB Background: To understand how the high-affinity IgE receptor (Fc epsilon RI) communicates with downstream effecters, we focused on exploring the functional importance of the Fc epsilon RI-mediated formation and localization of a signaling complex that contains the hematopoietic cell-specific scaffolding protein linker for activation of T cells (LAT) and the guanine nucleotide exchange factor Vav1. Methods: Using the mast cell line RBL-2H3, we explored the localization of these proteins by confocal microscopy and cell fractionation. Additionally, the mechanism of function and the importance of LAT and Vav1 to mast cells was studied in genetically disrupted mice and in mast cells derived from their bone marrow. Results: We found that LAT, Vav1 and the adapter molecule SLP-76 associated in detergent-resistant microdomains (lipid rafts) found in the plasma membrane upon Fc epsilon RI stimulation. In the absence of LAT, mast cells showed a remarkable loss of the secretory response and reduced cytokine responses. Vav1 deficiency also affected secretion, al though not to the extent of LAT deficiency, and inhibited IL-2 and IFN-gamma production. LAT- and Vav1-deficient mice showed reduced blood histamine levels after a systemic anaphylaxis challenge as compared to their normal counterparts. Conclusions: The results demonstrate that LAT is a central mediator in IgE receptor signaling by regulating multiple signaling pathways that affect mast cell degranulation and cytokine production. Vav1, a component of this LAT-containing signaling complex, regulates a specific subset of these responses. Copyright (C) 2001 S. Karger AG,Basel. C1 NIAMSD, Sect Chem Immunol, NIH, Bethesda, MD 20892 USA. RP Rivera, J (reprint author), NIAMSD, Sect Chem Immunol, NIH, Bethesda, MD 20892 USA. NR 22 TC 19 Z9 19 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD JAN-MAR PY 2001 VL 124 IS 1-3 BP 137 EP 141 DI 10.1159/000053692 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 422MU UT WOS:000168123200037 PM 11306950 ER PT J AU Okayama, Y Hagaman, DD Woolhiser, M Metcalfe, DD AF Okayama, Y Hagaman, DD Woolhiser, M Metcalfe, DD TI Further characterization of Fc gamma RII and Fc gamma RIII expression by cultured human mast cells SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 23rd Symposium of the Collegium Internationale Allergologicum (CIA 2000) CY MAY 18-23, 2000 CL HAKONE, JAPAN DE mast cells; Fc receptors ID NEGATIVE REGULATION; PHOSPHATASE SHIP; IGG RECEPTOR; ACTIVATION AB Background: We have reported that resting human mast cells exhibit minimal expression for Fc gamma RI, a nd that interferon-gamma will upregulate this expression. The expression of Fc gamma RII and Fc gamma RIII by human mast cells remains to be fully examined. Methods: To investigate Fc gamma RII and Fc gamma RIII expression, we determined mRNA and protein expression of Fc gamma RII and Fc gamma RIII in human peripheral blood CD34+ derived cultured mast cells by RT-PCR and flow cytometry. The expression of Fc gamma RII and Fc gamma RIII in intact and permeabilized mast cells was also compared. We measured histamine release to monitor mast cell degranulation following cross-linking of Fc gamma RII. Results: We found by RT-PCR that resting human mast cells exhibit mRNA for Fc gamma RIIA, Fc gamma RIIb1, Fc gamma RIIb2 and Fc gamma RIII but not Fc gamma RIIC. FAGS analysis of Fc gamma receptors in intact versus permeabilized mast cells showed expression of Fc gamma RII to be 42.2 +/- 3.9% and this was unchanged by permeabilization. Fc gamma RIII protein expression was minimal and this was also unchanged by permeabilization. Aggregation of Fc gamma RII on human mast cells led to no significant degranulation as evidenced by histamine release. Conclusions: In addition to Fc gamma RI expression, human mast cells express Fc gamma RIIA, Fc gamma RIIb1, Fc gamma RIIb2 and Fc gamma RIII mRNA, and significant surface expression of Fc gamma RII. Aggregation of Fc gamma RII on cultured human mast cells in this model was not followed by histamine release. Copyright (C) 2001 S. Karger AG, Basel. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Okayama, Y (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C206,10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. NR 7 TC 33 Z9 34 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD JAN-MAR PY 2001 VL 124 IS 1-3 BP 155 EP 157 DI 10.1159/000053696 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 422MU UT WOS:000168123200041 PM 11306954 ER PT J AU Lin, HM Martelli, MP Bierer, BE AF Lin, HM Martelli, MP Bierer, BE TI The involvement of the proto-oncogene p120 c-Cbl and ZAP-70 in CD2-mediated T cell activation SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE Crk; NF-AT; phosphatidylinositol-3 kinase; signal transduction; Syk; T lymphocytes; ZAP-70 ID PHOSPHOTYROSINE-BINDING DOMAIN; GROWTH-FACTOR RECEPTOR; TYROSINE KINASE-ACTIVITY; NEGATIVE REGULATOR; INTERLEUKIN-2 PROMOTER; PROTOONCOGENE PRODUCT; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; JURKAT CELLS; CD2 AB The CD2 co-receptor expressed on the surface of T lymphocytes is able to stimulate T cell activation, proliferation and cytokine production in the absence of direct engagement of the antigen-specific TCR, Engagement of human CD2 by mitogenic pairs of anti-CDP mAb induces tyrosine phosphorylation of a number of intracellular proteins including a 120 kDa phosphoprotein that we identify as the proto-oncogene c-Cbl, Rapidly tyrosine phosphorylated following stimulation of a number of cell surface receptors, c-Cbl is an adaptor protein that has been shown to associate with a complex of intracellular signaling molecules, and to mediate both positive and negative regulatory effects. Here we show that, like TCR-CD3 stimulation, stimulation of CD2 enhanced the association of c-Cbl with both Crk(L) and the p85 subunit of phosphatidylinositol-3 kinase, Overexpression of wild-type c-Cbl protein inhibited both CD2- and CD3-induced NF-AT transcriptional activity, suggesting that CD2 signaling is also negatively regulated by c-Cbl, The inhibitory effect of c-Cbl depended upon its N-terminal phosphotyrosine-binding domain, the domain that has been shown to be required for inhibition of the Syk/ZAP-70 family kinases. In Syk(-) Jurkat T cells stably expressing wild-type ZAP-70, CD2 stimulation induced only a minimal increase in ZAP-70 tyrosine phosphorylation. Nevertheless, ZAP-70 kinase was required for CDS-mediated NF-AT transcriptional activity. Thus, CDS-mediated NF-AT transcriptional activity appears to depend upon ZAP-70/Syk kinases and to be negatively regulated by c-Cbl. C1 NHLBI, Lab Lymphocyte Biol, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Bierer, BE (reprint author), NHLBI, Lab Lymphocyte Biol, NIH, 10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA. RI Martelli, Maria Paola/I-5618-2012 NR 68 TC 9 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JAN PY 2001 VL 13 IS 1 BP 13 EP 22 DI 10.1093/intimm/13.1.13 PG 10 WC Immunology SC Immunology GA 394ZU UT WOS:000166554900003 PM 11133830 ER PT J AU Takahashi, M Nakagawa, Y Berzofsky, JA Takahashi, H AF Takahashi, M Nakagawa, Y Berzofsky, JA Takahashi, H TI Counter-regulation of cytolytic activity and cytokine production in HIV-1-specific murine CD8(+) cytotoxic T lymphocytes by free antigenic peptide SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE cytokines; cytolytic molecules; cytotoxic T lymphocyte; free antigenic peptide; HIV-1IL-2R beta ID CLASS-I; DOWN-REGULATION; COGNATE PEPTIDES; CO-STIMULATION; MHC MOLECULE; CELLS; VIRUS; EXPRESSION; INDUCTION; INTERLEUKIN-2 AB We have reported previously that the cytolytic activity of murine CD8(+) cytotoxic T lymphocytes (CTL) specific for HIV-1 gp160 envelope glycoprotein was markedly inhibited by brief exposure to the free minimal antigenic peptide (I-10: 10mer peptide from gp160) by direct binding to class I MHC molecules of specific CTL in the absence of antigen-presenting cells (APC), Here, we show that treatment of such CTL with the peptide induced not only the inhibition of cytolytic activity but also IL-SR beta down-modulation, followed by the inhibition of IL-2-dependent growth, The peptide-mediated inhibition and restoration of expression of IL-SRP were well correlated with changes in both cytolytic activity and IL-2-dependent growth of the CTL, Since enzymatic activity of granzyme B, and mRNA expression of granzyme B and perforin were significantly reduced in peptide-treated CTL, the inhibition of cytolytic activity was mainly caused by the exhaustion of cytolytic molecules. Moreover, treatment of the CTL with the epitopic peptide resulted in production of high levels of IL-2, IFN-gamma, tumor necrosis factor-alpha and MIP-1 beta in the culture supernatant. Maximum amounts of cytokines were obtained in the culture supernatant when the level of cytolytic activity was the lowest. Thus, although the CTL temporarily lost their cytolytic activities, they simultaneously gained the abilities to produce cytokines for activation of various cell populations, These changes induced by free antigenic peptide in CD8(+) CTL reveal an interesting counter-regulation between their cytolytic activities and cytokine production. C1 Nippon Med Sch, Dept Microbiol & Immunol, Bunkyo Ku, Tokyo 1138602, Japan. NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Takahashi, H (reprint author), Nippon Med Sch, Dept Microbiol & Immunol, Bunkyo Ku, 1-1-5 Sendagi, Tokyo 1138602, Japan. NR 33 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JAN PY 2001 VL 13 IS 1 BP 43 EP 51 DI 10.1093/intimm/13.1.43 PG 9 WC Immunology SC Immunology GA 394ZU UT WOS:000166554900006 PM 11133833 ER PT J AU Unden, AL Elofsson, S Viigimaa, M Johansson, J Knox, S AF Unden, AL Elofsson, S Viigimaa, M Johansson, J Knox, S TI A psychosocial comparison of 35- and 55-year-old men and women in Sweden and Estonia: The Swestonia cardiovascular risk factor study SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE quality of life; self-rated health; depression; CHD ID ISCHEMIC-HEART-DISEASE; MYOCARDIAL-INFARCTION; PERCEIVED HEALTH; TOTAL MORTALITY; EASTERN-EUROPE; HOPELESSNESS; DEPRESSION; MORBIDITY; DIVIDE AB During the past decade, the incidence of coronary heart disease (CHD) has declined in the United States and in Western Europe, but has increased in Eastern Europe and in many non-European countries. This study is a baseline comparison of psychosocial factors in a random sample of 35-year-old and 55-year-old men and women from Tartu, Estonia and Sollentuna, Sweden, who will be followed longitudinally to investigate CHD risk. One hundred men and women from each country in each age group were invited by letter to participate in a study of risk factors for CHD. Complete data were available for 279 Estonians and 272 Swedes. All participants were given the same physical examination and answered the same self-report questionnaires concerning demographics, lifestyle, and psychosocial factors. In general, Swedish men and women in both age groups rated their quality of life higher than Estonians. Self-reported health and depressive symptoms, both of which have predicted CHD risk, were also worse in Estonians than in Swedes. The psychosocial differences found here, together with the lack of major differences in traditional risk factors, re fleet the results found in other East-West comparisons. Implications for CHD risk are discussed. C1 Karolinska Hosp, Res Ctr Gen Med, Dept Gen Med, S-17176 Stockholm, Sweden. Stockholm Univ, Inst Social Work, S-10691 Stockholm, Sweden. Tartu Univ Hosp, Dept Cardiol, Tartu, Estonia. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Unden, AL (reprint author), Karolinska Hosp, Res Ctr Gen Med, Dept Gen Med, Borgmastarvillan, S-17176 Stockholm, Sweden. NR 36 TC 1 Z9 1 U1 2 U2 3 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PY 2001 VL 8 IS 2 BP 149 EP 162 DI 10.1207/S15327558IJBM0802_05 PG 14 WC Psychology, Clinical SC Psychology GA 445BN UT WOS:000169438400005 ER PT J AU Kodjabachian, L Karavanov, AA Hikasa, H Hukriede, NA Aoki, T Taira, M Dawid, IB AF Kodjabachian, L Karavanov, AA Hikasa, H Hukriede, NA Aoki, T Taira, M Dawid, IB TI A study of Xlim1 function in the Spemann-Mangold organizer SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article; Proceedings Paper CT International Workshop Molecular Nature of the Gastrula Organizing Center - 75 Years after Spemann and Mangold CY MAY 24-26, 1999 CL MADRID, SPAIN DE Spemann-Mangold organizer; Xenopus; Xlim1; anteroposterior axis; axial mesoderm ID DORSALIZING MORPHOGENETIC PROTEIN; XENOPUS CEMENT GLAND; HOMEOBOX GENE; LIM DOMAINS; TRANSCRIPTION FACTORS; VISCERAL ENDODERM; VENTRAL MESODERM; MOLECULAR NATURE; HEAD INDUCTION; WNT AB The Spemann-Mangold organizer is required in amphibian embryos to coordinate cell fate specification, differentiation of dorsal cell types and morphogenetic movements at early stages of development. A great number of genes are specifically expressed within the organizer, most of them encoding secreted proteins and transcription factors. The challenge is now to uncover genetic cascades and networks of interactions between these genes, in order to understand how the organizer functions. The task is immense and requires loss-of-function approaches to test the requirement for a given factor in a specific process. For transcription factors, it is possible to generate inhibitory molecules by fusing the DNA binding region to a repressor or activator domain, which should in principle antagonize the activity of the endogenous protein at the level of the DNA targets. We used this strategy to design activated and inhibitory forms of the LIM homeodomain transcription factor Lim1,which is encoded by an organizer gene involved in head development, as revealed by analyses of knockout mice. We found that Lim1 is a transcriptional activator, and can trigger dorso-anterior development upon ventral expression of hyperactive forms, in which Ldb1 is fused to Lim1. Using inhibitory Lim1 fusion proteins, we found that Lim1, or genes closely related to it, is required for head formation as well as for notochord development. Go-expression experiments revealed that Lim1 is required downstream of the early organizer factor Siamois, first, to establish the genetic program of the organizer and second, to mediate the action of organizer agents that are responsible for blocking ventralizing activities in the gastrula. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Mol Embryol Lab, Tokyo 113, Japan. Japan Sci & Technol Corp, CREST, Yokohama, Kanagawa, Japan. RP Dawid, IB (reprint author), NICHHD, Mol Genet Lab, NIH, Bldg 6B,Rm 420,9200 Rockville Pike, Bethesda, MD 20892 USA. RI Aoki, Tazu/F-5051-2011; TAIRA, MASANORI/G-4923-2014 NR 52 TC 14 Z9 15 U1 0 U2 0 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2001 VL 45 IS 1 SI SI BP 209 EP 218 PG 10 WC Developmental Biology SC Developmental Biology GA 414HB UT WOS:000167659600017 PM 11291848 ER PT J AU Unda, FJ Iehara, N De-Vega, S De-La-Fuente, M Vilaxa, A Yamada, Y AF Unda, FJ Iehara, N De-Vega, S De-La-Fuente, M Vilaxa, A Yamada, Y TI Study of novel genes involved in odontoblast and ameloblast differentiation SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article; Proceedings Paper CT 3rd Congress of the Spanish-Society-of-Developmental-Biology CY SEP 16-19, 2001 CL MALAGA, SPAIN SP Spanish Soc Dev Biol, Univ Malaga, Minist Educ Cultura & Deporte, Minist Ciencia & Technol, Junta Andaluc, Excmo Ayuntamiento Malaga, Fund Ramon Areces AB Teeth are organs which develop by inductive interactions between dental epithelium and subjacent mesenchyme. In order to identify genes involved in odontoblast and ameloblast differentiation, we have constructed a cDNA library from E19.5 mouse molars. In this work, we report partial DNA sequences of 10 non-characterized genes. In addition, we show cell expression of the transcripts in mouse embryo molars by in situ hybridization. We discuss the role of these genes in cell differentiation. C1 Univ Basque Country, Fac Med & Dent, Dept Cell Biol, E-48940 Leioa, Vizcaya, Spain. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. Univ Tarapaca, Dept Biol & Salud, Arica, Chile. RP Unda, FJ (reprint author), Univ Basque Country, Fac Med & Dent, Dept Cell Biol, E-48940 Leioa, Vizcaya, Spain. NR 6 TC 0 Z9 0 U1 2 U2 15 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2001 VL 45 SU 1 BP S103 EP S104 PG 2 WC Developmental Biology SC Developmental Biology GA 470HZ UT WOS:000170866700037 ER PT J AU Eisenhauer, E Dancey, J AF Eisenhauer, E Dancey, J TI Impact of new non-cytotoxics in the treatment of ovarian cancer SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article; Proceedings Paper CT 3rd International Sumposium on Advanced Ovarian Cancer: Optimal Therapy Update CY MAR 09, 2001 CL VALENCIA, SPAIN SP European Soc Med Oncol, Spanish Soc Med Oncol, Grp Espanol Invest & Canc Ovario, Soc Espanola Ginecol & Obstet ID ENDOTHELIAL GROWTH-FACTOR; HUMAN-BREAST-CANCER; FACTOR RECEPTOR; PROGNOSTIC-SIGNIFICANCE; FACTOR EXPRESSION; PATIENT SURVIVAL; CARCINOMA; ONCOGENE; AMPLIFICATION; ANGIOGENESIS AB Over the last decade, a number of new cytotoxic chemotherapy agents have shown evidence of antitumor activity in patients with ovarian carcinoma. These agents are currently being evaluated in large multinational randomized trials to determine whether their addition either concurrently or sequentially to standard paclitaxel and carboplatin regimens will result in improved survival. Whether these new combinations will provide additional benefit may be uncertain; however, it is certain that additional toxicity will limit the continued evaluation of the strategy of adding cytotoxics together. New approaches to improve the systemic therapy of ovarian cancer need to be explored. The next decade will see many trials of non-cytotoxics having a wide range of subcellular and extracellular targets. Many of these targets are abnormally expressed in a variety of solid tumors; thus, it is expected that many of these agents will be appropriate to evaluate in patients with ovarian carcinoma. Based on promising data from preclinical and early clinical studies as well as the presumed applicability of these targets to ovarian carcinoma, the inhibitors of growth factor receptors such as epidermal growth factor receptor and inhibitors of angiogenesis are of particular interest. Despite the interest of the investigators, the rapid evaluation of these target-specific non-cytotoxics is limited by the lack of accurate information on the expression of target in ovarian tumors and the relevance of target expression and its modulation to this tumor type. Early clinical trials are being designed to address these concerns; however, the clinical impact of non-cytotoxic agents in epithelial ovarian carcinoma patients must await the completion of randomized evaluations in combination with standard chemotherapeutic regimens. C1 Queens Univ, NCIC Clin Trials Grp, IND Program, Kingston, ON K7L 3N6, Canada. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Eisenhauer, E (reprint author), Queens Univ, NCIC Clin Trials Grp, IND Program, 82-84 Barrie St, Kingston, ON K7L 3N6, Canada. NR 22 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PY 2001 VL 11 SU 1 BP 68 EP 72 DI 10.1046/j.1525-1438.2001.11(suppl.1)sup1068.x PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 458EZ UT WOS:000170181400014 PM 11489007 ER PT J AU Wang, H Liu, CY Song, YL Gordon, D Alavi, MZ Moore, S AF Wang, H Liu, CY Song, YL Gordon, D Alavi, MZ Moore, S TI Expression of metalloproteinases and its inhibitor in later stage of rabbit neointima development SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE matrix metalloproteinase; TIMP; ECM; neointima; atherosclerosis ID SMOOTH-MUSCLE CELLS; EXPLANTS 15 WEEKS; MATRIX METALLOPROTEINASES; TISSUE INHIBITORS; BALLOON CATHETER; FIBROBLAST CELLS; VASCULAR INJURY; DEENDOTHELIALIZATION; COLLAGENASE; MIGRATION AB Neointima formation after arterial de-endothelialization refers not only to smooth muscle cell (SMC) migration and proliferation, but also involves extracellular matrix (ECM) metabolism. Most studies regarding the role of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in neointima have focused on the early phase of vascular remodeling. In this study, we examined the expression of MMP and TIMP in rabbit aortic neointima at a relatively late stage of lesion development, between 4 and 12 weeks after initial de-endothelialization. Northern blot analysis revealed expression of steady-state MMP-9 mRNA was increased up to the 4th week and MMP-2 mRNA to the 12th week after de-endothelialization. In situ hybridization shown that MMP positive cells were predominantly distributed in arterial neointima. Expression of TIMP-1 mRNA was continuously up-regulated up to the 12th week and TIMP-1 positive cells, primarily SMCs, were also localized to the neointimal tissue. Alteration at mRNA level was accompanied by that at protein level, as assessed by SDS-PAGE zymography for MMPs and immunoblotting for TIMP-1. The profile of alteration at protein level correlated well with that at mRNA level. These data suggest that synthesis of MMPs and TIMP is a prolonged process and arterial SMC is a major source of MMP production in arterial neointima. Enhanced synthesis of MMPs and TIMPs at late stage of neointimal development may contribute to arterial ECM metabolism. C1 Pfizer Global Res & Dev, Cardiovasc Therapeut, Ann Arbor Labs, Ann Arbor, MI 48105 USA. NIMH, Bethesda, MD 20892 USA. McGill Univ, Dept Pathol, Montreal, PQ, Canada. RP Wang, H (reprint author), Pfizer Global Res & Dev, Cardiovasc Therapeut, Ann Arbor Labs, Ann Arbor, MI 48105 USA. NR 36 TC 11 Z9 11 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD JAN PY 2001 VL 7 IS 1 BP 105 EP 112 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 383UQ UT WOS:000165901800018 PM 11115618 ER PT J AU Kenworthy, L Smith, BD Fedio, P Smith, DA Reese, K AF Kenworthy, L Smith, BD Fedio, P Smith, DA Reese, K TI Hemispheric specialization in emotion: Attention, arousal, and EEG activation in unilateral temporal lobe epilepsy SO INTERNATIONAL JOURNAL OF NEUROSCIENCE LA English DT Article DE epilepsy; EEG; emotion; lateralization ID FACIAL EMOTION; PERSONALITY; DEPRESSION; EXPERIENCE; EXPRESSION; PATTERNS; STIMULI; ANXIETY; LESION AB To investigate the neural processing of emotion in right and left temporal lobe epilepsy (TLE), we monitored EEG during neutral and emotionally positive and negative auditory stimulation. Left TLE patients displayed increased right lateralization and a negative emotional stimulus rating bias, while right TLE patients did not. This EEG arousal and negative affect may reflect deactivated inhibition of the right hemisphere, symptomatically expressed as arousal and anxiety. Failure to increase lateralization to emotional stimuli in right TLE may reflect compromised emotional attention/arousal centers in the right hemisphere. Results support a two-dimensional theory of the neural processing of emotion. C1 Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Smith, BD (reprint author), Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. EM smith@psyc.umd.edu NR 27 TC 6 Z9 6 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0020-7454 EI 1563-5279 J9 INT J NEUROSCI JI Int. J. Neurosci. PY 2001 VL 107 IS 3-4 BP 279 EP 293 DI 10.3109/00207450109150690 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 428DA UT WOS:000168444800009 PM 11328696 ER PT J AU Marchetti, A Buttitta, F Pellegrini, S Bertacca, G Callahan, R AF Marchetti, A Buttitta, F Pellegrini, S Bertacca, G Callahan, R TI Reduced expression of INT-6/eIF3-p48 in human tumors SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE int-6; eIF3; mouse mammary tumor virus; lung cancer; breast cancer ID K-RAS MUTATIONS; BRONCHIOLOALVEOLAR CARCINOMAS; MALIGNANT TRANSFORMATION; PROTEIN-KINASE; SUBUNIT; INT-6; ONCOPROTEIN; BREAST; CANCER; VIRUS AB The int-6 gene, originally identified as a common integration site for the mouse mammary tumor virus (MMTV) in mouse mammary tumors, encodes the p48 component of the eukaryotic translation initiation factor-3 (eIF3-p48). Int-6/eIF3-p48 is expressed in all adult tissues which have been tested and early in embryonic development. Int-6/eIF3-p48 has been highly conserved throughout evolution and the deduced amino acid sequence of the human gene product is identical to the mouse protein. Viral insertions at the Int-6/eIF3-p48 locus in mouse mammary tumors result in production of chimeric Int-6/eIF3-p48/MMTV products that may act as dominant negative oncoproteins. Int-6/eIF3-p48 has also been identified as a human protein that binds to the human T-cell leukemia virus type I Tax oncoprotein. The role of Int-6/eIF3-p48 in human carcinogenesis is unknown at the present time. Tn this study we have examined Int-6/eIF3-p48 gene status and expression in two of the most common forms of cancer in humans, breast and lung tumors. Sixty-two breast carcinomas and 78 non-small cell lung carcinomas (NSCLC) were investigated. LOH at the Int-6/eIF3-p48 locus was observed in 5 (21%) of 24 informative breast tumors and 10 (29%) of 34 informative lung tumors. A reduced expression of Int-6/eIF3-p48 was seen in 23 (37%) of breast cancer samples and 24 (31%) of NSCLC samples. An association between Int-6/eIF3-p48 expression and LOH at the Int-6/eIF3-p48 locus was observed, Int-6/eIF3-p48 expression was not related to commonly used pathological parameters in breast cancer patients, while in NSCLC patients Int-6/eIF3-p48 expression was mainly seen in adenocarcinomas (P<0.0001). In conclusion, our data show for the first time a decreased expression of Int-6/eIF3-p48 in a consistent portion of human breast and lung carcinomas, frequently associated with LOH at the Int-6/eIF3-p48 locus. Additional studies on larger series of tumor specimens with long-term follow-up are needed to determine whether Int-6/eIF3-p48 expression may represent a new prognostic or predictive marker. C1 Univ Gabriele DAnnunzio, Dept Oncol & Neurosci, Mol Pathol Sect, Chieti, Italy. Univ Pisa, Dept Oncol, Pisa, Italy. NIH, Tumor Immunol & Biol Lab, Oncogenet Sect, Bethesda, MD USA. RP Marchetti, A (reprint author), Univ Chieti, Osped SS Annunziata, Dept Oncol & Neurosci, Via Valignani, I-66100 Chieti, Italy. RI Pellegrini, Silvia/C-3770-2011 NR 21 TC 53 Z9 56 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JAN PY 2001 VL 18 IS 1 BP 175 EP 179 PG 5 WC Oncology SC Oncology GA 383TM UT WOS:000165899000025 PM 11115556 ER PT J AU Diwan, BA Henneman, JR Nims, RW AF Diwan, BA Henneman, JR Nims, RW TI Enhancement of N-nitrosodiethylamine-initiated hepatocarcinogenesis by phenytoin in male F344/NCr rats at a dose causing maximal induction of CYP2B SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE cytochrome(s) P450 induction; F344 rats; liver tumor promotion; phenytoin ID ENZYME-INDUCTION; LIVER-MICROSOMES; PROMOTION; DRUGS AB The effect of the clinically important anticonvulsant phenytoin (DPH) on hepatocarcinogenesis of male F344/NCr rats initiated with a single i.p. dose of N-nitrosodiethylamine (75 mg/kg b.w.) was studied. Beginning 2 weeks post-initiation, the rats received control diet or diet containing 500 or 1500 ppm DPH or 500 ppm phenobarbital, At 52 weeks age, the incidences (and multiplicities, in units of tumors per tumor-bearing rat) of hepatocellular adenomas were 0%, 17% (1 +/- 0), 42% (1.8 +/- 0.8), or 67% (2.5 +/- 1.9) in rats exposed to N-nitrosodiethylamine alone, or the carcinogen followed by 500 ppm DPH, 1500 ppm DPH, or 500 ppm phenobarbital, respectively. Between 53 and 79 weeks of age, 39% of rats receiving N-nitrosodiethylamine alone developed multiple (1.5 +/- 0.8) hepatocellular adenomas, A similar incidence (41%) occurred in the rats administered the carcinogen followed by 500 ppm DPH, The incidence of hepatocellular adenomas (88% and 89%) was significantly greater in rats exposed to N-nitrosodiethylamine followed by 1500 ppm DPH or 500 ppm phenobarbital, respectively, Multiplicities of hepatocellular adenomas were significantly greater than the control value in rats fed 1500 ppm DPH or 500 ppm phenobarbital (5.9 +/- 4.8 and 10.1 +/- 6.7, respectively), but not in the rats receiving 500 ppm DPH (2.3 +/- 1.6), No rats exposed to N-nitrosodiethylamine alone or the carcinogen followed by 500 ppm DPH developed hepatocellular carcinomas, while hepatocellular carcinomas occurred in 29% or 67% of the rats given 1500 ppm DPH or 500 ppm phenobarbital, respectively, following initiation, Increases in hepatic CYP2B-mediated benzyloxyresorufin O-dealkylation activity in rats exposed to 500 and 1500 ppm DPH for 2 or 23 weeks were similar to 50% and similar to 100%, respectively, of the maximal induction caused by 500 ppm phenobarbital, Thus, in the rat model, DPH enhanced N-nitrosodiethylamine-initiated hepatocarcinogenesis when administered at a dose causing maximal CYP2B induction. C1 NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Diwan, BA (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Bldg 538,Room 205E, Frederick, MD 21702 USA. EM bdiwan@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-56000] NR 30 TC 5 Z9 5 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 EI 1092-874X J9 INT J TOXICOL JI Int. J. Toxicol. PY 2001 VL 20 IS 2 BP 81 EP 87 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 429KU UT WOS:000168516800005 PM 11354469 ER PT J AU Huang, XM Lawler, CP Lewis, MM Nichols, DE Mailman, RB AF Huang, XM Lawler, CP Lewis, MM Nichols, DE Mailman, RB TI D-1 dopamine receptors SO INTERNATIONAL REVIEW OF NEUROBIOLOGY, VOL 48 SE INTERNATIONAL REVIEW OF NEUROBIOLOGY LA English DT Review ID LONG-TERM POTENTIATION; IDENTIFIED STRIATONIGRAL NEURONS; LEVODOPA-INDUCED DYSKINESIAS; SENSITIVE ADENYLATE-CYCLASE; SUBTYPE-SPECIFIC ANTIBODIES; PROTEIN-COUPLED RECEPTORS; SPATIAL WORKING-MEMORY; CENTRAL-NERVOUS-SYSTEM; BINDING-SITE CREVICE; INSITU HYBRIDIZATION HISTOCHEMISTRY C1 Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Med Chem, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Ctr Neurosci, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Neurol, Chapel Hill, NC 27599 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Purdue Univ, Sch Pharm & Pharmacal Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. RP Mailman, RB (reprint author), Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. OI Mailman, Richard/0000-0003-1353-2738 FU NICHD NIH HHS [HD07201, HD03310]; NIDA NIH HHS [DA07244]; NIMH NIH HHS [MH42705, MH33127, MH40537, MH53356]; NINDS NIH HHS [NS39036] NR 402 TC 22 Z9 23 U1 2 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 J9 INT REV NEUROBIOL PY 2001 VL 48 BP 65 EP 139 DI 10.1016/S0074-7742(01)48014-7 PG 75 WC Neurosciences SC Neurosciences & Neurology GA BS72U UT WOS:000170995200003 PM 11526741 ER PT J AU Varterasian, ML Pemberton, PA Hulburd, K Rodriguez, DH Murgo, A Al-Katib, AM AF Varterasian, ML Pemberton, PA Hulburd, K Rodriguez, DH Murgo, A Al-Katib, AM TI Phase II study of bryostatin 1 in patients with relapsed multiple myeloma SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE phase II; bryostatin 1; multiple myeloma; relapsed ID LARGE-CELL LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; VINCRISTINE; AGENTS AB Bryostatin 1, a macrocyclic lactone isolated from the marine bryozoan Bugula neritina, is a protein kinase C (PKC) modulator which has shown both preclinical and clinical activity in lymphoid malignancies. We conducted a phase II trial of bryostatin 1 administered at a dose of 120 mug/m(2) by 72-h continuous infusion every 2 weeks in patients with relapsed multiple myeloma. Treatment was well tolerated with myalgias constituting the primaray toxicity. There were no responses in nine evaluable patients. The preclinical anti-lymphoid activity is strong enough to support further exploration of bryostatin 1 in different schedules and in combination therapy for multiple myeloma. C1 Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. NCI, Invest Drug Branch, CTEP, DCTDC, Rockville, MD USA. RP Varterasian, ML (reprint author), Pfizer Global Res & Dev, 2800 Pymouth Rd, Ann Arbor, MI USA. NR 9 TC 33 Z9 34 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PY 2001 VL 19 IS 3 BP 245 EP 247 DI 10.1023/A:1010676719178 PG 3 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 457XY UT WOS:000170164000007 PM 11561682 ER PT J AU Argiris, A Heald, P Kuzel, T Foss, FM DiStasio, S Cooper, DL Arbuck, S Murren, JR AF Argiris, A Heald, P Kuzel, T Foss, FM DiStasio, S Cooper, DL Arbuck, S Murren, JR TI Phase II trial of 9-aminocamptothecin as a 72-h infusion in cutaneous T-cell lymphoma SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE 9-aminocamptothecin (9-AC); cutaneous T-cell; lymphoma; indwelling catheter-related infection ID COLLOIDAL DISPERSION FORMULATION; METASTATIC COLORECTAL-CARCINOMA; MYCOSIS-FUNGOIDES; SOLID TUMORS; SEZARY-SYNDROME; CHEMOTHERAPY; XENOGRAFTS; CANCER; ADULT; 9-DIMETHYLAMINOMETHYL-10-HYDROXYCAMPTOTHECIN AB Purpose: To evaluate the role of 9-aminocamptothecin (9-AC), a synthetic camptothecin analog, in advanced cutaneous T-cell lymphoma (CTCL). Methods: Eligible patients had stage IIB-IV CTCL. 9-AC was infused over 72 h at a dose of 1,100 mug/m(2) per day (approximately 46 mug/m(2)/h) every 2 weeks, with granulocyte-colony stimulating factor (G-CSF) support. Results: Twelve patients received a total of 30 cycles of 9-AC. Nine patients had stage IV disease, 5 patients had circulating Sezary cells, and 2 patients had evidence of tranformation to a large cell lymphoma. Most of the patients were heavily pretreated: 10 had received prior chemotherapy (83%), 5 of whom had received 2 or more prior regimens, including a patient who had received high-dose chemotherapy, and 7 had previously received total-skin electron beam therapy. The study was prematurely terminated due to substantial toxicity. Six patients (50%) developed an indwelling central venous catheter-related infection, 5 during a period of neutropenia. Three patients died due to sepsis 4-8 weeks after their last 9-AC treatment. Two of these patients had a previous history of bacterial sepsis. Four patients (33%) developed grade IV thrombocytopenia. Two partial responses were observed (response rate 17%), but the duration of response was brief, 4-8 weeks. Conclusion: 9-AC at this schedule and route of administration had activity but resulted in an unacceptable rate of complicated neutropenia and septic deaths in heavily pretreated patients with advanced CTCL who are susceptible to catheter-related infections. C1 Northwestern Univ, Sch Med, Div Hematol Oncol, Chicago, IL 60611 USA. Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA. Yale Univ, Sch Med, New Haven, CT USA. Boston Univ, Sch Med, New England Med Ctr, Boston, MA 02118 USA. NCI, Invest Drug Branch, Rockville, MD USA. RP Argiris, A (reprint author), Northwestern Univ, Sch Med, Div Hematol Oncol, 676 N St Clair St,Suite 850, Chicago, IL 60611 USA. NR 31 TC 6 Z9 6 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PY 2001 VL 19 IS 4 BP 321 EP 326 DI 10.1023/A:1010613912335 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 457XZ UT WOS:000170164100007 PM 11561692 ER PT J AU Detrick, B Nagineni, CN Grillone, LR Anderson, KP Henry, SP Hooks, JJ AF Detrick, B Nagineni, CN Grillone, LR Anderson, KP Henry, SP Hooks, JJ TI Inhibition of human cytomegalovirus replication in a human retinal epithelial cell model by antisense oligonucleotides SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PHOSPHOROTHIOATE OLIGONUCLEOTIDE; VIRUS RETINITIS; OCULAR MANIFESTATIONS; ANTIVIRAL ACTIVITY; GENE-EXPRESSION; RNA; COMPLEMENTARY; GANCICLOVIR; PHARMACOKINETICS; RESISTANCE AB PURPOSE. The antiviral activity of first and second generation antisense oligonucleotides on human cytomegalovirus (CMV) replication was evaluated in two cell systems, the traditional system on human fibroblasts and on human retinal pigment epithelial (HRPE) cell culture system. METHODS. TO evaluate CMV replication strategies within the retina, an HRPE cell system permissive to CMV replication was developed. In this study, the antiviral activity of the antisense oligonucleotides, ISIS 2922 (Vitraven) and ISIS 13312, was evaluated in the traditional fibroblast antiviral assay and in the HRPE cell system. Antiviral activity was measured by evaluating inhibition of virus induced cytopathic effect, virus plaque formation, and virus gene expression. RESULTS. Both oligonucleotides produced concentration-dependent inhibition of CMV cytopathic effect and CMV plaque formation in both human RPE cells and a human fibroblast cell line, MRC-5. The oligonucleotide, ISIS 2922, demonstrated a mean 50% inhibitory concentration (IC50) of 0.04 and 0.24 muM in HRPE and MRC-5 cells, respectively. The second-generation oligonucleotide, ISIS 13312, yielded similar results with IC50 levels of 0.05 and 0.3 muM in HRPE and MRC-5 cells, respectively. Similar findings were obtained with a CMV clinical isolate. in addition, initiation of effective oligonucleotide treatment could be introduced 6 days after CMV infection in HRPE cells, whereas, in the fibroblast cell line, oligonucleotide treatment was only effective up to 3 days after infection. Semiquantitative RT-PCR analysis demonstrated significant inhibition of CMV intermediate early and late mRNAs by both oligonucleotides. CONCLUSIONS. These studies demonstrate that HRPE cells were significantly more sensitive than fibroblasts to the antiviral actions of ISIS 2922 and ISIS 13312. Moreover, the data indicate that the anti-CMV potency of the two oligonucleotides was similar. The enhanced potency of these oligonucleotides in HRPE cells may be associated with a delay in viral gene transcription and slow viral replication and spread in these cells. C1 NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. ISIS Pharmaceut, Carlsbad, CA 92008 USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. RP Hooks, JJ (reprint author), NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bldg 10,Room 6N228,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 34 TC 30 Z9 32 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2001 VL 42 IS 1 BP 163 EP 169 PG 7 WC Ophthalmology SC Ophthalmology GA 388CG UT WOS:000166159400023 PM 11133862 ER PT J AU Curcio, CA Millican, CL Bailey, T Kruth, HS AF Curcio, CA Millican, CL Bailey, T Kruth, HS TI Accumulation of cholesterol with age in human Bruch's membrane SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; HUMAN ATHEROSCLEROTIC LESIONS; AMERICAN-HEART-ASSOCIATION; LIPID-RICH CORE; MACULAR DEGENERATION; EXTRACELLULAR-MATRIX; MORPHOMETRIC ANALYSIS; VASCULAR-LESIONS; PLASMA-PROTEINS; GRADING SYSTEM AB PURPOSE. To determine the cholesterol composition of normal human Bruch's membrane and choroid as a function of age and retinal location. METHODS. Human eyes with grossly normal maculas were preserved <4 hours after donor death. Cryosections of retina and choroid from the macula and temporal equator were stained with filipin to reveal esterified (EC) or unesterified (UC) cholesterol (n = 20, 17-92 years). Filipin fluorescence in Bruch's membrane was quantified with digital microscopy. Maculas were prepared for lipid-preserving electron microscopy (n = 18, 16-87 years) and for ultrastructural analysis after lipid extraction (n = 2, 85 and 89 years). Punches of macular Bruch's membrane, 8 mm in diameter, were assayed for cholesterol content by enzymatic fluorometry (n = 10, >70 years). RESULTS. EC and UC in Bruch's membrane increased with age in the macula. EC was sevenfold higher in macula than in periphery. Sixty percent of total cholesterol was esterified, and Bruch's membrane EC was 16- to 40-fold enriched relative to plasma. Solid, 100-nm-diameter particles occupied >30% of the inner collagenous layer in eyes >60 years. Cholesterol accumulated in choroidal arteries and in small age-related drusen. CONCLUSIONS. Human Bruch's membrane ages like arterial intima and other connective tissues for which plasma lipoproteins are the known source of extracellular cholesterol. Age-related maculopathy and atherosclerotic cardiovascular disease may share common pathogenic mechanisms. C1 Univ Alabama, Dept Ophthalmol, Birmingham, AL 35294 USA. Univ Alabama, Dept Physiol Opt, Birmingham, AL 35294 USA. NHLBI, Sect Expt Atherosclerosis, Bethesda, MD 20892 USA. RP Curcio, CA (reprint author), Univ Alabama, Dept Ophthalmol, Eye Fdn Hosp, Rm H20,700 S 18th St, Birmingham, AL 35294 USA. FU NEI NIH HHS [P30EY03039, EY06109] NR 79 TC 245 Z9 251 U1 0 U2 8 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2001 VL 42 IS 1 BP 265 EP 274 PG 10 WC Ophthalmology SC Ophthalmology GA 388CG UT WOS:000166159400039 PM 11133878 ER PT B AU Sokoloff, L AF Sokoloff, L BE Fukuuchi, Y Tomita, M Koto, A TI Historical review of developments in the field of cerebral blood flow and metabolism SO ISCHEMIC BLOOD FLOW IN THE BRAIN SE KEIO UNIVERSITY SYMPOSIA FOR LIFE SCIENCE AND MEDICINE LA English DT Proceedings Paper CT 6th Keio-University International Symposium for Life Science and Medicine CY 1999 CL TOKYO, JAPAN SP Keio Univ Med Sci Fund DE brain; cerebral circulation; functional brain imaging; energy metabolism; metabolic mapping ID GLUCOSE-UTILIZATION; INTRAVENOUS (H2O)-O-15; SENSORY STIMULATION; BRAIN AB Brain (cerebral) blood flow (CBF) and metabolism have long been subjects of great interest, but progress in their study awaited development of quantitative methods applicable to unanesthetized animals and man. The development of the nitrous oxide method by Kety and Schmidt (1948) revolutionized the field and led to much of our present knowledge of the physiology and pharmacology of CBF and energy metabolism in humans in health and disease. This method, however, measured only average CBF in the whole brain. This limitation was overcome by development of the autoradiographic [I-131]trifluoroiodomethane ((CF3I)-I-131) method by Kety and colleagues that measured local CBF simultaneously in all structures of the brain in conscious animals. Its autoradiograms provided visual images of the relative rates of CBF and led to the first demonstration of functional brain imaging (i.e., increases in CBF in structures of the cat visual system during retinal stimulation). The (CF3I)-I-131 method was later modified for use with C-14 autoradiography and a nonvolatile tracer, first [C-14] antipyrine and then [C-14]iodoantipyrine. This is the same method that was later adapted for use in humans with (H2O)-O-15 and positron emission tomography (PET) and is now commonly used. The (CF3I)-I-131 method and its derivatives were applied during uptake of tracer by cerebral tissues, but its basic principles apply equally well to clearance of the tracer from tissues. In 1949 Kety had reported a technique to determine local muscle blood flow by clearance of Na-24 injected into the tissue. This method was modified for use with radioactive gases, first Kr-85 and then Xe-133, both of which freely cross the blood-brain barrier, and this clearance method has been used to measure regional CBF at rest and during alteration in local functional activity in humans. Energy metabolism is a function of individual cells, but CBF serves regions of the brain and is sensitive to systemic factors (e.g., blood gas tensions, pH). Measurement of local energy metabolism could therefore be expected to provide better resolution and specificity in response to altered neuronal functional activity. Sokoloff and coworkers, employing quantitative autoradiography together with radioactive 2-deoxy-D-glucose (2-DG), developed a method to measure local cerebral glucose utilization (lCMR(glc)). They applied this method to localize and image local alterations in functional neuronal activity on the basis of changes in lCMR(glc) in many physiological, pharmacological, and pathological states and used it to define and quantify the relations between energy metabolism and functional and electrical activities in neural tissues. Because it employed autoradiography, the 2-DG method could not be used in humans. Therefore, Reivich and coworkers (1979) adapted the method for use in humans with Kuhl's Mark IV single photon section scanner and the gamma -emitting analogue of 2-DG, 2-deoxy-2-[F-18]fluoro-D-glucose ((18)FDG). F-18 is a positron emitter; and soon afterward Phelps, Kuhl, and coworkers (1979) modified the (18)FDG method for use with PET with its superior spatial resolution and quantification. This method has been widely used to study regional energy metabolism in brain and other organs in humans in health and disease. Magnetic resonance imaging (MRI) techniques that provide signals correlating with changes in local CBF have recently been developed. These techniques measure increase in proton signal that occur when paramagnetic deoxyhemoglobin levels are reduced in the region of interest. Because CBF transiently increases more than O-2 consumption when brain tissue is activated, the venous deoxyhemoglobin content is reduced, and the enhancement in local proton signal is displayed in computer-generated reconstructed images, it should be noted that any cause of arterial vasodilatation, even if blood flow is not increased (e.g., during autoregulatory response to hypotension), reduces venous blood and deoxyhemoglobin contents in accordance with the principles of the Munro-Kellie doctrine. Nevertheless, MRI-based functional brain imaging has become the most popular CBF-related technique in use today because of its noninvasiveness, lack of ionizing radiation, excellent spatial and temporal resolution, and repeatability. Although it may correlate with changes in CBF, however, it does not measure it. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. RP Sokoloff, L (reprint author), NIMH, Cerebral Metab Lab, Bldg 36,Room 1A-07, Bethesda, MD 20892 USA. NR 34 TC 7 Z9 7 U1 1 U2 1 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 37-3, HONGO 3-CHOME BONKYO-KU, TOKYO, 113, JAPAN BN 4-431-70292-X J9 KEIO UNIV SYMP LIFE PY 2001 VL 6 BP 3 EP 10 PG 8 WC Neurosciences SC Neurosciences & Neurology GA BS15A UT WOS:000168851000001 ER PT B AU Spatz, M Chen, Y Ohara, Y McCarron, RM AF Spatz, M Chen, Y Ohara, Y McCarron, RM BE Fukuuchi, Y Tomita, M Koto, A TI Brain microvasculature: Evidence for interactive endothelium-dependent responses induced by endothelin-1 and nitric oxide SO ISCHEMIC BLOOD FLOW IN THE BRAIN SE KEIO UNIVERSITY SYMPOSIA FOR LIFE SCIENCE AND MEDICINE LA English DT Proceedings Paper CT 6th Keio-University International Symposium for Life Science and Medicine CY 1999 CL TOKYO, JAPAN SP Keio Univ Med Sci Fund DE endothelial cells; intracellular Ca2+; signal transduction; cytoskeleton; ETA receptor antagonist ID CEREBROSPINAL-FLUID; CEREBRAL-ISCHEMIA; PHARMACOLOGY; CELLS; PATHOPHYSIOLOGY; PHYSIOLOGY; VASOSPASM; RECEPTORS; PEPTIDE AB Previous in vivo and in vitro studies demonstrated a functional interaction between endothelin-1 (ET-1) and nitric oxide (NO) at the level of ETA receptors. The present experiments were designed to examine the involvement of the signal transduction pathway in ET-1 and NO modulation of Ca2+ mobilization and cytoskeletal filament organization. The results indicate that ET-1-stimulated Ca2+ mobilization was inhibited by NO in endothelial cells (ECs) derived from human brain microvessels or capillaries. This effect by NO was mimicked by 8-bromo cyclic guanosine monophosphate (cGMP) and was prevented by an inhibitor of guanylyl cyclase, ODQ, and an inhibitor of protein kinase G, Rp-8-pCPT-cGMP. NO and 8-bromo-cGMP modulation of Ca2+ mobilization were similarly affected by agents known to regulate other signals downstream of ET-1 stimulation. These findings demonstrate the close relation between NO and ET-1 in ECs. This interaction takes place at the level of the ET-1 receptor and downstream messenger pathway, leading to rapid changes in intracellular Ca2+. Therefore, ECs have the capacity to regulate endothelium-dependent responses involved in maintaining capillary tone, microcirculation, and blood-brain barrier function. C1 NIH, Natl Inst Neurol & Communicat Dis, Stroke Branch, Bethesda, MD 20892 USA. RP Spatz, M (reprint author), NIH, Natl Inst Neurol & Communicat Dis, Stroke Branch, Bldg 10,36 Convent Dr,MSC 4128, Bethesda, MD 20892 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 37-3, HONGO 3-CHOME BONKYO-KU, TOKYO, 113, JAPAN BN 4-431-70292-X J9 KEIO UNIV SYMP LIFE PY 2001 VL 6 BP 313 EP 318 PG 6 WC Neurosciences SC Neurosciences & Neurology GA BS15A UT WOS:000168851000038 ER PT B AU Rifkind, JM Abugo, OO Nagababu, E Ajmani, RS Metter, EJ Demehin, A Manoharan, PT Balagopalakrishna, C Crest, FJ AF Rifkind, JM Abugo, OO Nagababu, E Ajmani, RS Metter, EJ Demehin, A Manoharan, PT Balagopalakrishna, C Crest, FJ BE Fukuuchi, Y Tomita, M Koto, A TI Role of altered blood properties in the propagation of ischemic blood flow: Contribution of aging and oxidative stress SO ISCHEMIC BLOOD FLOW IN THE BRAIN SE KEIO UNIVERSITY SYMPOSIA FOR LIFE SCIENCE AND MEDICINE LA English DT Proceedings Paper CT 6th Keio-University International Symposium for Life Science and Medicine CY 1999 CL TOKYO, JAPAN SP Keio Univ Med Sci Fund DE oxidative stress; hemoglobin autoxidation; aging; hemorheology; blood flow ID ERYTHROCYTE DEFORMABILITY; COBALAMIN DEFICIENCY; HYDROGEN-PEROXIDE; HEME POCKET; HEMOGLOBIN; SUPEROXIDE; OXYGEN; DEGRADATION; POPULATION; PREVALENCE AB The red blood cell (RBC) undergoes enhanced oxidative processes at reduced oxygen pressures. They originate from the dramatic increase in the rates of autoxidation for partially oxygenated hemoglobin and the associated production of superoxide. The basis for this form of oxidative stress and its ramifications have been reviewed. The release of superoxide by hemoglobin has been implicated in heme degradation, damage to the RBC membrane,leakage of reactive oxygen molecules into the plasma, and the potential beneficial release of NO from S-nitrosylated hemoglobin. It has further been shown that these oxidative reactions can escape the RBC antioxidant defenses when taking place on the hemoglobin bound to the RBC membrane. During aging increased hypoxia results in enhanced oxidative stress, which is consistent with large RBCs, decreased deformability and increased viscosity. Furthermore, the deficiency in vitamin B-12 may limit the level of S-nitrosylation decreasing the release of NO associated with hemoglobin autoxidation. The synergistic relation coupling hypoxia-oxidative stress-altered RBC properties further increases hypoxia and provides a mechanism for exacerbated decrements in flow during aging or pathological conditions, which can result in ischemic stress. The relevance of these hemorheological and oxidative perturbations has been validated by blood flow velocity studies of the cerebral and carotid arteries. C1 NIA, Lab Cellular & Mol Biol, Mol Dynam Sect, Baltimore, MD 21224 USA. RP Rifkind, JM (reprint author), NIA, Lab Cellular & Mol Biol, Mol Dynam Sect, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 29 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 37-3, HONGO 3-CHOME BONKYO-KU, TOKYO, 113, JAPAN BN 4-431-70292-X J9 KEIO UNIV SYMP LIFE PY 2001 VL 6 BP 369 EP 380 PG 12 WC Neurosciences SC Neurosciences & Neurology GA BS15A UT WOS:000168851000046 ER PT B AU Hallenbeck, JM AF Hallenbeck, JM BE Fukuuchi, Y Tomita, M Koto, A TI TNF alpha, endothelium, and microcirculation in stroke initiation, progression, and tolerance SO ISCHEMIC BLOOD FLOW IN THE BRAIN SE KEIO UNIVERSITY SYMPOSIA FOR LIFE SCIENCE AND MEDICINE LA English DT Proceedings Paper CT 6th Keio-University International Symposium for Life Science and Medicine CY 1999 CL TOKYO, JAPAN SP Keio Univ Med Sci Fund DE tumor necrosis factor-alpha (TNF alpha); stroke; endothelium; microcirculation; ischemic tolerance ID TUMOR-NECROSIS-FACTOR; FOCAL CEREBRAL-ISCHEMIA; SPONTANEOUSLY HYPERTENSIVE RAT; PERIPHERAL-CIRCULATION; RISK-FACTORS; AGED RATS; BRAIN; INJURY; BLOOD; INTERLEUKIN-1 AB Tumor necrosis factor-alpha (TNF alpha) can activate luminal endothelium in intraparenchymal segments of the cerebral vasculature and predispose those segments to thrombosis. Spontaneously hypertensive rats (SHRs) have increased numbers of perivascular macrophages around their intraparenchymal brain vessels and release increased amounts of TNF alpha in response to lipopolysaccharide (LPS). They develop more strokes after LPS administration than normotensive rats. In addition, normotensive Sprague-Dawley rats can be made susceptible to strokes induced by LPS by activating their macrophages with bacillus Calmette Guerin. TNF alpha is acutely expressed following focal cerebral ischemia, and blocking its activity with TNFbp has been demonstrated to reduce infarct volume in several models of focal ischemia. These studies indicate that TNF alpha participates in secondary brain injury during the early hours of ischemia. Evidence has been developed that TNF alpha is involved in the signaling pathways that regulate the development of tolerance to ischemia. Although tolerance is generally attributed to an increase in neuronal resistance to ischemia, studies of the microcirculation after a preconditioning exposure that generated the requisite TNF alpha activity in SHRs revealed that preservation of microcirculatory perfusion is a feature of the tolerant state. C1 NIH, Stroke Branch, NINCDS, Bethesda, MD 20892 USA. RP Hallenbeck, JM (reprint author), NIH, Stroke Branch, NINCDS, 36 Convent Dr,MSC 4128,Bldg 36,Room 4A03, Bethesda, MD 20892 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 37-3, HONGO 3-CHOME BONKYO-KU, TOKYO, 113, JAPAN BN 4-431-70292-X J9 KEIO UNIV SYMP LIFE PY 2001 VL 6 BP 393 EP 400 PG 8 WC Neurosciences SC Neurosciences & Neurology GA BS15A UT WOS:000168851000048 ER PT J AU Levine, AM Berhane, K Masri-Lavine, L Sanchez, ML Young, M Augenbraun, M Cohen, M Anastos, K Newman, M Gange, SJ Watts, H AF Levine, AM Berhane, K Masri-Lavine, L Sanchez, ML Young, M Augenbraun, M Cohen, M Anastos, K Newman, M Gange, SJ Watts, H TI Prevalence and correlates of anemia in a large cohort of HIV-infected women: Women's interagency HIV study SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; anemia; women ID IMMUNODEFICIENCY-VIRUS INFECTION; UNITED-STATES; WHITE WOMEN; ERYTHROPOIETIN; BLACK; AIDS; EPIDEMIOLOGY; THALASSEMIA; SURVIVAL AB Anemia is a common manifestation of HIV infection, occurring in aproximately 30% of patients with asymptomatic infection and in as many as 75% to 80% of those with AIDS. Anemia has been associated with decreased quality of life and decreased survival. We performed a cross-sectional study nested within a multicenter prospective cohort study to describe the prevalence of anemia in 2056 HIV-infected and 569 HIV-negative women as well as to define the demographic, clinical, immunologic, and virologic correlates of anemia among HIV-infected women. A total of 37% of HIV-positive women and 17% of HIV-negative women had hemoglobin levels < 12 g/dl (p <.001). Factors associated with anemia in HIV-positive and HIV-negative women included mean corpuscular volume (MCV) < <80 fl (p < .001) and black race (p <.001). Among HIV-infected women, multivariate logistic analyses revealed that African American race (p < .0001), MCV < 80 fl (p < .0001), CD3 count < 200 per microliter (p < .0001), higher HIV RNA in plasma (p = .02), current use of ZDV (p = .01), and history of clinical AIDS (p = .004) were all independent predictors of anemia. These data indicate that worsening parameters of HIV disease are associated with anemia among HIV-infected women. Black women and women with Low MCV values are at increased risk for anemia independent of HIV status. C1 Univ So Calif, Sch Med, Los Angeles, CA USA. Georgetown Univ, Washington, DC USA. Maimonides Med Ctr, Brooklyn, NY 11219 USA. Cook Cty Hosp, Chicago, IL 60612 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Johns Hopkins Sch Hyg & Publ Hlth, Baltimore, MD USA. NIH, Rockville, MD USA. RP Levine, AM (reprint author), Univ So Calif, Norris Canc Hosp, 1441 Eastlake Ave,MS 34, Los Angeles, CA 90033 USA. OI Gange, Stephen/0000-0001-7842-512X FU NIAID NIH HHS [UO1-AI-34994, UO1-AI-35004, UO1-AI-31834] NR 37 TC 71 Z9 74 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD JAN 1 PY 2001 VL 26 IS 1 BP 28 EP 35 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 393YQ UT WOS:000166497600004 PM 11176266 ER PT J AU Moolchan, ET Umbricht, A Epstein, D AF Moolchan, ET Umbricht, A Epstein, D TI Therapeutic drug monitoring in methadone maintenance: Choosing a matrix SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE methadone maintenance; opioid addiction; pharmacokinetics ID PLASMA-PROTEIN BINDING; STEADY-STATE PHARMACOKINETICS; HUMAN LIVER-MICROSOMES; N-DEMETHYLATION; MASS-SPECTROMETRY; CLINICAL PHARMACOKINETICS; ALPHA-1-ACID GLYCOPROTEIN; LIQUID-CHROMATOGRAPHY; COCAINE ABSTINENCE; ADAPTIVE-CHANGES AB Methadone maintenance is the premier pharmacological treatment for opioid addiction, but it is rarely informed by evidence-based practice guidelines for dosage monitoring and adjustment. Such guidelines ale crucial because the pharmacokinetics of methadone vary greatly among patients, and this variation may account for differences in treatment outcome. We review the pharmacokinetics of methadone and factors that may alter it (including drug interactions, disease states, and idiosyncratic differences among patients). Also reviewed are prospects for therapeutic drug monitoring (TDM) of methadone in plasma, urine, sweat, and saliva. Due to its ease of collection and its presumed representation of the bioavailable free-fraction of methadone, saliva may be a promising matrix. However, saliva methadone concentrations are influenced by salivary pH, and future studies are needed to determine how to control for that. Administrative, medical, and social implications of methadone TDM are briefly discussed. C1 NIDA, Dept Hlth & Human Serv, NIH, IRP,Clin Pharmacol & Therapeut Res Branch, Baltimore, MD 21224 USA. RP Moolchan, ET (reprint author), NIDA, Dept Hlth & Human Serv, NIH, IRP,Clin Pharmacol & Therapeut Res Branch, 5500 Nathan Shock Dr,POB 5180, Baltimore, MD 21224 USA. RI Reis, Aline/G-9573-2012 NR 96 TC 23 Z9 24 U1 0 U2 1 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2001 VL 20 IS 2 BP 55 EP 73 PG 19 WC Substance Abuse SC Substance Abuse GA 423QT UT WOS:000168188800005 PM 11318398 ER PT J AU Mezinskis, JP Honos-Webb, L Kropp, F Somoza, E AF Mezinskis, JP Honos-Webb, L Kropp, F Somoza, E TI The measurement of craving SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE substance dependence; substance withdrawal syndrome; psychological test ID COMPULSIVE DRINKING SCALE; CUE EXPOSURE; SMOKING CESSATION; WITHDRAWAL SYMPTOMS; OPIATE ADDICTS; DRUG-USE; CONDITIONED-RESPONSES; INITIAL VALIDATION; ALCOHOL DEPENDENCE; COCAINE DEPENDENCE AB This article presents an overview of the definition and measurement of "craving" as it is applied to drug and alcohol abuse research. Examples of craving measures are described and organized in terms of whether they structure craving as a single factor or as a multifactorial construct. The application of craving scales in cue-conditioning studies, in medication treatment trials, and as outcome measures in other treatment studies is considered. It is concluded that no single craving scale, or type of scale, has unequivocal support, because few studies have administered more than one scale to the same population. It is suggested that our understanding of craving will be advanced by designing studies that compare and contrast several craving scales within the same study. Likewise, craving is only one possible cause of relapse. Future studies should compare several alternate relapse mechanisms within the same study. (C) 2001 by The Haworth Press, Inc. All rights reserved. C1 Vet Adm Med Ctr, Cincinnati Addict Res Ctr, NIDA VA Medicat Dev Res Unit, Cincinnati, OH 45220 USA. RP Mezinskis, JP (reprint author), Vet Adm Med Ctr, Cincinnati Addict Res Ctr, NIDA VA Medicat Dev Res Unit, 3200 Vine St, Cincinnati, OH 45220 USA. FU NIDA NIH HHS [1YO1 DA 50038-00] NR 79 TC 36 Z9 36 U1 6 U2 11 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2001 VL 20 IS 3 BP 67 EP 85 PG 19 WC Substance Abuse SC Substance Abuse GA 488HZ UT WOS:000171923000007 PM 11681594 ER PT J AU Allen, JP Litten, RZ Fertig, JB AF Allen, JP Litten, RZ Fertig, JB TI Biochemical markers as aids for evaluating medications for alcohol treatment SO JOURNAL OF ADDICTIVE DISEASES LA English DT Meeting Abstract C1 NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2001 VL 20 IS 2 MA 1A BP 123 EP 123 PG 1 WC Substance Abuse SC Substance Abuse GA 423QT UT WOS:000168188800011 ER PT J AU Cadet, JL Tate, K Better, W Bolla, K AF Cadet, JL Tate, K Better, W Bolla, K TI Cognitive deficits with chronic marijuana abuse SO JOURNAL OF ADDICTIVE DISEASES LA English DT Meeting Abstract C1 NIDA, Mol Neuropsychiat Sect, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2001 VL 20 IS 2 MA 8A BP 130 EP 130 PG 1 WC Substance Abuse SC Substance Abuse GA 423QT UT WOS:000168188800018 ER PT J AU Cadet, JL Tate, K Better, W Foreman, J Herning, RI AF Cadet, JL Tate, K Better, W Foreman, J Herning, RI TI Marijuana abuse alters thyroid function SO JOURNAL OF ADDICTIVE DISEASES LA English DT Meeting Abstract C1 NIDA, Mol Neuropsychiat Sect, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2001 VL 20 IS 2 MA 9A BP 131 EP 131 PG 1 WC Substance Abuse SC Substance Abuse GA 423QT UT WOS:000168188800019 ER PT J AU Harlan, WR AF Harlan, WR TI New opportunities and proven approaches in complementary and alternative medicine research at the National Institutes of Health SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article; Proceedings Paper CT Symposium on Scientific Integration of Western Medicine and Complementary, Alternative-Mind, Body Medicine CY JUL, 1999 CL SEOUL, SOUTH KOREA AB This presentation describes some of the issues that arise when applying the clinical-trial approach of conventional medicine to complementary and alternative medicine (CAM) modalities. Conventional medicine has been making, the evolution to using an evidence base and to making recommendations only when the evidence is strong. The National Center for Complementary Medicine (NCCAM), one of twenty-five Institutes or Centers of the National Institutes of Health (NIH), is working to hold CAM to the same high standards, not by rejecting previous CAM research, but by building on that strong evidence base of what works and what is safe. The process for conventional drug and device development follows an orderly process of preclinical studies (usually on animals), phase I, phase II, and phase III studies (with the large human clinical trial phase taking place in phase III). Today, the randomized controlled trial is recognized as providing the highest level of scientific evidence. This conventional medicine approach to development is now being used to develop complementary and alternative therapies. For instance, the discovery and development of Taxol (Bristol-Meyers Squibb, New York, NY), an extract from the bark of the Pacific yew tree that is now a widely used chemotherapeutic agent, followed the conventional pathway to approval and marketing. But for most CAM products, the pathway is not so straightforward. Most CAM therapies are traditional therapies or new products that are already available to the public. Most of what is known about these therapies is of an anecdotal nature. There has been little isolation of the active principals from the crude product and there has usually been no preclinical testing. This presentation details various approaches and programs that address how to plan and conduct a rigorous clinical trial of a CAM product. And, while it takes a good deal of persistence and a strong focus on what are the critical principals in a trial, I conclude that it is possible to apply randomized controlled trials to most of the CAM modalities. C1 NIMH, Ctr Neurosci, DSIR, Publ Hlth Serv,NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Harlan, WR (reprint author), NIMH, Ctr Neurosci, DSIR, Publ Hlth Serv,NIH, Room 7117,6001 Execut Blvd, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PY 2001 VL 7 SU 1 BP S53 EP S59 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 516HN UT WOS:000173548000011 PM 11822636 ER PT J AU Harlan, WR AF Harlan, WR TI Research on complementary and alternative medicine using randomized controlled trials SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article; Proceedings Paper CT Symposium on Scientific Integration of Western Medicine and Complementary, Alternative-Mind, Body Medicine CY JUL, 1999 CL SEOUL, SOUTH KOREA AB In 1998, the National Institutes of Health (NIH) formed the National Center for Complementary and Alternative Medicine (NCCAM) from what had formerly been the Office of Alternative Medicine. This presentation opens with a brief discussion on the history of the NIH and the development of CAM at the NIH before moving on to the work of the NCCAM. The NCCAM is moving toward an integration of CAM therapies into conventional medicine, when there is evidence for the value of CAM. One of twenty-five institutes or centers at the NIH, the NCCAM looks at evidence-based medicine and public health. In this context, "public health" means educating the public about its health. The NCCAM supports training to conduct research and plays an important role in disseminating information to the public and to health providers about what works and what is safe. This evolves into the concept of evidence-based medical and public-health practices, that is, making decisions on the basis of evidence from scientifically rigorous studies that are sufficiently large to provide a confident estimate of biologically and medically important benefits and risks. In the hierarchy of generating scientific evidence, randomized controlled trials are considered the "gold standard." The NCCAM entertains proposals for studies that come spontaneously from investigators, or, upon identifying an existing need that is not being met by the investigative community, the NCCAM can initiate a request for proposals. Every proposal is subjected to a rigorous application and review process. Another possible step in the assessment of the evidence from clinical trials is to do a systematic analysis of several studies to bring together all the information that is available. Systematic reviews of smaller studies that individually might have an insufficient sample size can assist in making treatment decisions, but, importantly, they can lead the NCCAM in the development of future, definitive studies. Training, to conduct research is especially important to CAM. This presentation outlines several approaches the NCCAM has to training (see http://nccam.nih.gov). C1 NIMH, DSIR, Ctr Neurosci, Publ Hlth Serv,NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Harlan, WR (reprint author), NIMH, DSIR, Ctr Neurosci, Publ Hlth Serv,NIH, Room 7117,6001 Execut Blvd, Bethesda, MD 20892 USA. NR 3 TC 6 Z9 6 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PY 2001 VL 7 SU 1 BP S45 EP S52 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 516HN UT WOS:000173548000010 PM 11822635 ER PT J AU Harlan, WR AF Harlan, WR TI Papers from the Symposium on Scientific Integration of Western Medicine and Complementary center dot Alternative Mind center dot Body Medicine Seoul, Korea SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Editorial Material C1 NIMH, DSIR, Ctr Neurosci, Publ Hlth Serv,NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Harlan, WR (reprint author), NIMH, DSIR, Ctr Neurosci, Publ Hlth Serv,NIH, Room 7117,6001 Execut Blvd, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PY 2001 VL 7 SU 1 BP S1 EP S4 PG 4 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 516HN UT WOS:000173548000001 PM 11822622 ER PT J AU Shen, J AF Shen, J TI Research on the neurophysiological mechanisms of acupuncture: Review of selected studies and methodological issues SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article; Proceedings Paper CT Symposium on Scientific Integration of Western Medicine and Complementary, Alternative-Mind, Body Medicine CY JUL, 1999 CL SEOUL, SOUTH KOREA ID DIFFERENT FREQUENCIES; ELECTROACUPUNCTURE; BRAIN; NALOXONE; STIMULATION; ANALGESIA; GENES AB This presentation reviews studies that contribute to an understanding of the neurophysiological mechanisms of acupuncture. A 1973 study, using volunteer medical students, looked into acupuncture's analgesic effect on experimentally induced pain and suggests that humoral factors may mediate acupuncture-induced analgesia. In a study of the possible role of the cerebrospinal fluid transmission of pain suppression effects of acupuncture, cerebrospinal fluid from acupuncture-treated rabbits was infused into recipient rabbits. The analgesic effect was observed in the recipient rabbits, suggesting that acupuncture-induced analgesia may be mediated by substances released in the cerebrospinal fluid. Studies of electroacupuncture in rats revealed that both low-frequency and high-frequency stimulation could induce analgesia, but that there are differential effects of low- and high-frequency acupuncture on the types of endorphins released. In another study, low-frequency electroacupuncture, given as median nerve stimulation in cats, was shown to protect the myocardium. by inhibiting sympathetic pressor response and increasing myocardial oxygen demand. The development of neuroimaging tools, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), make noninvasive studies of acupuncture's effects on human brain activity possible. Studies using PET have shown that thalamic asymmetry present among patients suffering from chronic pain was reduced after the patients underwent acupuncture treatment. Other studies, using fMRI, have pointed to relationships between particular acupoints. and visual-cortex activation. These powerful new tools open the possibility to new scientific studies of this ancient therapy. C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Shen, J (reprint author), NIH, Ctr Clin, Bldg 10-6S Room 240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 15 TC 45 Z9 49 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PY 2001 VL 7 SU 1 BP S121 EP S127 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 516HN UT WOS:000173548000019 PM 11822627 ER PT J AU Pellegrini, L Passer, BJ Canelles, M Lefterov, I Ganjei, JK Fowlkes, BJ Koonin, EV D'Adamio, L AF Pellegrini, Luca Passer, Brent J. Canelles, Matilde Lefterov, Ilyia Ganjei, J. Kelly Fowlkes, B. J. Koonin, Eugene V. D'Adamio, Luciano TI PAMP and PARL, two novel putative metalloproteases interacting with the COOH-terminus of Presenilin-1 and-2 SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Presenilin; A beta PP; Alzheimer's disease; Rhomboid; metalloprotease AB The familial Alzheimer's disease gene products, presenilin-1 and presenilin-2 (PS1 and PS2), are involved in amyloid beta-protein precursor processing (A beta PP), Notch receptor signaling, and programmed cell death. However, the molecular mechanisms by which presenilins regulate these processes remain unknown. Clues about the function of a protein can be obtained by seeing whether it interacts with another protein of known function. Using the yeast two-hybrid system, we identified two proteins that interact and colocalize with the presenilins. One of these newly detected presenilin-interacting proteins belongs to the FtsH family of ATP-dependent proteases, and the other one belongs to Rhomboid superfamily of membrane proteins that are highly conserved in eukaryotes, archaea and bacteria. Based on the pattern of amino acid residues conservation in the Rhomboid superfamily, we hypothesize that these proteins possess a metal-dependent enzymatic, possibly protease activity. The two putative proteases interacting with presenilins could mediate specific proteolysis of membrane proteins and contribute to the network of interactions in which presenilins are involved. C1 [Pellegrini, Luca; Passer, Brent J.; Canelles, Matilde; Ganjei, J. Kelly; Fowlkes, B. J.; D'Adamio, Luciano] NIH, Cellular & Mol Immunol Lab, Bethesda, MD 20892 USA. [Lefterov, Ilyia] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA. [Koonin, Eugene V.] Natl Lib Med, NCBI, Bethesda, MD 20892 USA. RP D'Adamio, L (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM ldadamio@aecom.yu.edu NR 52 TC 45 Z9 46 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2001 VL 3 IS 2 BP 181 EP 190 PG 10 WC Neurosciences SC Neurosciences & Neurology GA V23ID UT WOS:000208335600003 ER PT J AU Sklare, DA Konrad, HR Maser, JD Jacob, RG AF Sklare, DA Konrad, HR Maser, JD Jacob, RG TI Special issue on the interface of balance disorders and anxiety - An introduction and overview SO JOURNAL OF ANXIETY DISORDERS LA English DT Editorial Material ID PANIC DISORDER; VESTIBULAR DYSFUNCTION; COMMUNITY SAMPLE; DIZZINESS; ABNORMALITIES; AGORAPHOBIA; SYMPTOMS; VERTIGO; PEOPLE C1 Natl Inst Deafness & Other Commun Disorders, Div Extramural Res, Vestibular Sci Branch, Bethesda, MD 20892 USA. So Illinois Univ, Sch Med, Dept Surg, Springfield, IL USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst, Pittsburgh, PA USA. RP Sklare, DA (reprint author), Natl Inst Deafness & Other Commun Disorders, Div Extramural Res, Vestibular Sci Branch, Room 400C,6120 Execut Blvd,MSC-7180,Execut Plaza, Bethesda, MD 20892 USA. NR 25 TC 16 Z9 16 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD JAN-APR PY 2001 VL 15 IS 1-2 BP 1 EP 7 DI 10.1016/S0887-6185(00)00039-6 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 433BX UT WOS:000168736400001 PM 11388353 ER PT J AU Balaban, CD Thayer, JF AF Balaban, CD Thayer, JF TI Neurological bases for balance-anxiety links SO JOURNAL OF ANXIETY DISORDERS LA English DT Article; Proceedings Paper CT Workshop on the Interface of Balance Disorders and Anxiety CY SEP 15-16, 1997 CL WASHINGTON, D.C. SP Natl Inst Deafness & Other Commun Disorders, NIMH, NIH, Off Rare Dis DE vertigo; balance disorder; vestibular system; agoraphobia; anxiety disorder; monoamines ID MEDIAL VESTIBULAR NUCLEUS; CEREBELLAR PURKINJE-CELLS; CENTRAL AMYGDALOID NUCLEUS; AUTONOMIC NERVOUS-SYSTEM; RAT LOCUS-COERULEUS; PHASEOLUS-VULGARIS-LEUKOAGGLUTININ; GASTRIC MYOELECTRICAL ACTIVITY; CONDITIONED TASTE-AVERSION; MIDBRAIN RAPHE NUCLEI; PARABRACHIAL NUCLEUS AB This review paper examines neurologic bases of links between balance control and anxiety based upon neural circuits that are shared by pathways that mediate autonomic control, vestibule-autonomic interactions, and anxiety. The core of this circuitry is a parabrachial nucleus network, consisting of the parabrachial nucleus and its reciprocal relationships with the extended central amygdaloid nucleus, infralimbic cortex, and hypothalamus. Specifically, the parabrachial nucleus is a site of convergence of vestibular information processing and somatic and visceral sensory information processing in pathways that appear to be involved in avoidance conditioning, anxiety, and conditioned fear. Monoaminergic influences on these pathways are potential modulators of both effects of vigilance and anxiety on balance control and the development of anxiety and panic. This neurologic schema provides a unifying framework for investigating the neurologic bases for comorbidity of balance disorders and anxiety. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Neurobiol, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. RP Balaban, CD (reprint author), 107 EEI Bldg,200 Lothrop St, Pittsburgh, PA 15213 USA. OI Balaban, Carey/0000-0002-3570-3844 FU NIDCD NIH HHS [1P01 DC03417, R01 DC 00739] NR 158 TC 177 Z9 183 U1 4 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD JAN-APR PY 2001 VL 15 IS 1-2 BP 53 EP 79 DI 10.1016/S0887-6185(00)00042-6 PG 27 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 433BX UT WOS:000168736400004 PM 11388358 ER PT J AU Tanaka, M Malakoff, ME Bennett-Gates, D Zigler, E AF Tanaka, M Malakoff, ME Bennett-Gates, D Zigler, E TI Development of an outerdirected style of problem solving in individuals with and without mental retardation SO JOURNAL OF APPLIED DEVELOPMENTAL PSYCHOLOGY LA English DT Article DE Mental retardation; Mental retardation; fear of failure; Mental retardation; personality in; Outerdirectedness; Developmental-difference controversy AB Outerdirected behavior in a discrimination learning task was examined in 55 individuals with mental retardation at three CA levels: children, adolescents, and adults. These groups were compared to each other and to 55 mental age (MA)-matched individuals without mental retardation. Adults with mental retardation required more trials to reach criterion and showed higher levels of outerdirectedness than did mentally retarded children and adolescents despite adults having a higher MA. Nonretarded students showed the reverse trend, with the highest MA group requiring fewer trials to reach criterion and showing lower levels of outerdirectedness than the lowest MA group. These findings focus attention on the genesis of outerdirectedness and the possibility of preventing or remediating this unproductive style of problem solving. (C) 2001 Elsevier Science Inc, All rights reserved. C1 Yale Univ, Dept Psychol, New Haven, CT 06520 USA. NICHD, Bethesda, MD USA. Naruto Univ Educ, Kumamoto, Japan. RP Zigler, E (reprint author), Yale Univ, Dept Psychol, 2 Hillhouse Ave,POB 208205, New Haven, CT 06520 USA. NR 26 TC 1 Z9 2 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0193-3973 J9 J APPL DEV PSYCHOL JI J. Appl. Dev. Psychol. PY 2001 VL 22 IS 2 BP 191 EP 198 DI 10.1016/S0193-3973(01)00076-4 PG 8 WC Psychology, Developmental SC Psychology GA 436PB UT WOS:000168943300005 ER PT J AU Allhusen, V Appelbaum, M Belsky, J Booth, CL Bradley, R Brownell, C Burchinal, P Caldwell, B Campbell, S Clarke-Stewart, A Cox, M DeHart, G Friedman, SL Hirsh-Pasek, K Huston, A Jaeger, E Johnson, D Kelly, J Knoke, B Marshall, N McCartney, K O'Brien, M Owen, MT Payne, CC Phillips, D Pianta, R Randolph, S Robeson, WW Spieker, SJ Vandell, DL Wallner-Allen, KE Weinraub, M AF Allhusen, V Appelbaum, M Belsky, J Booth, CL Bradley, R Brownell, C Burchinal, P Caldwell, B Campbell, S Clarke-Stewart, A Cox, M DeHart, G Friedman, SL Hirsh-Pasek, K Huston, A Jaeger, E Johnson, D Kelly, J Knoke, B Marshall, N McCartney, K O'Brien, M Owen, MT Payne, CC Phillips, D Pianta, R Randolph, S Robeson, WW Spieker, SJ Vandell, DL Wallner-Allen, KE Weinraub, M CA NICHD Early Child Care Res Network TI Nonmaternal care and family factors in early development: An overview of the NICHD Study of Early Child Care SO JOURNAL OF APPLIED DEVELOPMENTAL PSYCHOLOGY LA English DT Article DE child care; longitudinal studies; childrearing practices; family-work relations ID AFTER-SCHOOL PROGRAMS; TEMPERAMENT QUESTIONNAIRE; INDIVIDUAL-DIFFERENCES; BEHAVIOR; PERFORMANCE; EXPERIENCES; QUALITY; INFANCY; WORK; LIFE AB In the most comprehensive US study to date about connections among child care experiences, family factors, and children's early development, 1100 children have been followed from birth through age 7. The study's intent is to describe family and child care/school contexts of children's development and examine associations between contextual variations and children's developmental outcomes in social-emotional, cognitive, and physical health domains. By age 3, over 90% of the children had experienced regular nonmaternal care, and over 50% were regularly spending over 30 hours/week in care. Economic factors, family characteristics, and maternal attitudes all influenced the amount and nature of early nonmaternal care. Observed quality of nonmaternal care consistently predicted social-emotional and cognitive-linguistic outcomes during the first 3 years of life. Amount of time spent in nonmaternal care predicted some social-emotional outcomes. Type and stability of nonmaternal care had limited predictive value. Family factors, including maternal sensitivity, quality of home environment, and income, were more consistent predictors of children's outcomes than any aspect of early nonmaternal care experiences. (C) 2001 Elsevier Science Inc. All rights reserved. C1 NICHHD, Publ Informat & Commun Branch, Bethesda, MD 20892 USA. RP Allhusen, V (reprint author), NICHHD, Publ Informat & Commun Branch, Bldg 31,2A32,31 Ctr Dr,MSC 2425, Bethesda, MD 20892 USA. RI Marshall, Nancy/C-3428-2012 NR 93 TC 101 Z9 101 U1 6 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0193-3973 J9 J APPL DEV PSYCHOL JI J. Appl. Dev. Psychol. PY 2001 VL 22 IS 5 BP 457 EP 492 PG 36 WC Psychology, Developmental SC Psychology GA 505ZJ UT WOS:000172945200002 ER PT J AU Geary, GG McNeill, AM Ospina, JA Krause, DN Korach, KS Duckles, SP AF Geary, GG McNeill, AM Ospina, JA Krause, DN Korach, KS Duckles, SP TI Genome and hormones: Gender differences in physiology - Selected contribution: Cerebrovascular NOS and cyclooxygenase are unaffected by estrogen in mice lacking estrogen receptor-alpha SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE cerebral circulation; estrogen receptor-alpha knockout mice; nitric oxide synthase; gonadal steroids; ovariectomy ID ENDOTHELIAL NITRIC-OXIDE; VASCULAR INJURY RESPONSE; DEFICIENT MICE; GENE DISRUPTION; MECHANISMS; EXPRESSION; CELLS; BETA AB Estrogen alters reactivity of cerebral arteries by modifying production of endothelium-dependent vasodilators. Estrogen receptors (ER) are thought to be involved, but the responsible ER subtype is unknown. ER-alpha knockout (alpha ERKO) mice were used to test whether estrogen acts via ER-alpha. Mice were ovariectomized, with or without estrogen replacement, and cerebral blood vessels were isolated 1 mo later. Estrogen increased levels of endothelial nitric oxide synthase and cyclooxygenase-1 in vessels from wild-type mice but was ineffective in alpha ERKO mice. Endothelium-denuded middle cerebral artery segments from all animals constricted when pressurized. In denuded arteries from alpha ERKO but not wild-type mice, estrogen treatment enhanced constriction. In endothelium-intact, pressurized arteries from wild-type estrogen-treated mice, diameters were larger compared with arteries from untreated wild-type mice. In addition, contractile responses to indomethacin were greater in arteries from wild-type estrogen-treated mice compared with arteries from untreated wild-type mice. In contrast, estrogen treatment of alpha ERKO mice had no effect on diameter or indomethacin responses of endothelium-intact arteries. Thus ER-alpha regulation of endothelial nitric oxide synthase and cyclooxygenase-1 pathways appears to contribute to effects of estrogen on cerebral artery reactivity. C1 Univ Calif Irvine, Coll Med, Dept Pharmacol, Irvine, CA 92697 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Duckles, SP (reprint author), Univ Calif Irvine, Coll Med, Dept Pharmacol, Irvine, CA 92697 USA. OI Korach, Kenneth/0000-0002-7765-418X FU NHLBI NIH HHS [R01 HL-50775] NR 31 TC 46 Z9 47 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PY 2001 VL 91 IS 5 BP 2391 EP 2399 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 486NN UT WOS:000171824000063 PM 11641386 ER PT J AU Fitzgerald, JR Monday, SR Foster, TJ Bohach, GA Hartigan, PJ Meaney, WJ Smyth, CJ AF Fitzgerald, JR Monday, SR Foster, TJ Bohach, GA Hartigan, PJ Meaney, WJ Smyth, CJ TI Characterization of a putative pathogenicity island from bovine Staphylococcus aureus encoding multiple superantigens SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ENTEROTOXIN-D; GENE; TOXIN; RECEPTOR; PLASMID; PCR AB Previous studies have demonstrated that a proportion of Staphylococcus aureus isolates from bovine mastitis coproduce toxic shock syndrome toxin (TSST) and staphylococcal enterotoxin C (SEC). In this study, molecular genetic analysis of one such strain, RF122, revealed the presence of a 15,891-bp putative pathogenicity island (SaPIbov) encoding the genes for TSST (tst), the SEC bovine variant (sec-bovine), and a gene (sel) which encodes an enterotoxin-like protein. The island contains 21 open reading frames specifying hypothetical proteins longer than 60 amino acids including an integrase-like gene. The element is bordered by 74-bp direct repeats at the left and right junctions, and the integration site lies adjacent to the 3' end of the GMP synthase gene (gmps) in the S. aureus chromosome, SaPIbov contains a central region of sequence identity with the previously characterized tst pathogenicity island SaPI1 (J. A. Lindsay et al,, Mel. Microbiol, 29:527-543, 1998), A closely related strain, RF120, of the same multilocus enzyme electrophoretic type, random amplified polymorphic DNA type, and ribotype, does not contain the island, implying that the element is mobile and that a recent insertion/deletion event has taken place. TSST and TSST/SEC-deficient mutants of S. aureus strain RF122 were constructed by allele replacement. In vitro bovine VP-specific lymphocyte expansion analysis by culture supernatants of wild-type strains and of tst and sec-bovine allele replacement mutants revealed that TSST stimulates BTB13-specific T cells whereas SEC-bovine stimulates BTB93-specific T cells. This suggests that the presence of SaPIbov may contribute to modulation of the bovine immune response. C1 Univ Dublin Trinity Coll, Moyne Inst Prevent Med, Dept Microbiol, Dublin 2, Ireland. Univ Dublin Trinity Coll, Dept Physiol, Dublin 2, Ireland. TEAGASC, Dairy Prod Res Ctr, Fermoy, Cork, Ireland. Univ Idaho, Dept Microbiol Mol Biol & Biochem, Moscow, ID 83844 USA. RP Fitzgerald, JR (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 34 TC 161 Z9 175 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2001 VL 183 IS 1 BP 63 EP 70 DI 10.1128/JB.183.1.63-70.2001 PG 8 WC Microbiology SC Microbiology GA 386UA UT WOS:000166078900007 PM 11114901 ER PT J AU Yoshinari, K Petrotchenko, EV Pedersen, LC Negishi, M AF Yoshinari, K Petrotchenko, EV Pedersen, LC Negishi, M TI Crystal structure-based studies of cytosolic sulfotransferase SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article DE sulfotransferases; sulfation; 3 '-phosphoadenosine-5 '-phosphosulfate; x-ray crystal structures ID SITE-DIRECTED MUTAGENESIS; HUMAN DOPAMINE SULFOTRANSFERASE; HUMAN ESTROGEN SULFOTRANSFERASE; MACULAR CORNEAL-DYSTROPHY; MOLECULAR-CLONING; PHENOL SULFOTRANSFERASE; MUTATIONAL ANALYSIS; AMINO-ACID; FLAVONOL 3-SULFOTRANSFERASE; SUBSTRATE-SPECIFICITY AB Sulfation is a widely observed biological reaction conserved from bacterium to human that plays a key role in various biological processes such as growth, development, and defense against adversities. Deficiencies due to the lack of the ubiquitous sulfate donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS) are lethal in humans. A large group of enzymes called sulfotransferases catalyze the transfer reaction of sulfuryl group of PAPS to the acceptor group of numerous biochemical and xenochemical substrates. Four X-ray crystal structures of sulfotransferases have now been determined: cytosolic estrogen, hydroxysteroid, aryl sulfotransferases, and a sulfotransferase domain of the Golgi-membrane heparan sulfate N-deacetylase/N-sulfotransferase 1. These have revealed the conserved core structure of the PAPS binding site, a common reaction mechanism, and some information concerning the substrate specificity. These crystal structures introduce a new era of the study of the sulfotransferases. (C) 2001 John Wiley & Sons, Inc. 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, POB 12233, Res Triangle Pk, NC 27709 USA. NR 61 TC 35 Z9 36 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2001 VL 15 IS 2 BP 67 EP 75 DI 10.1002/jbt.1 PG 9 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 419DU UT WOS:000167934700001 PM 11284047 ER PT J AU Dai, D Bai, R Hodgson, E Rose, RL AF Dai, D Bai, R Hodgson, E Rose, RL TI Cloning, sequencing, heterologous expression, and ch;characterization of murine cytochrome p450 3a25*(Cyp3a25), a testosterone 6 beta-hydroxylase SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article DE Cyp3a-25; cloning; sequencing; heterologous expression; metabolism and distribution; testosterone 6 beta-hydroxylase ID HUMAN-LIVER CYTOCHROME-P-450; ACTIVATE AFLATOXIN B-1; AMINO-ACID-SEQUENCES; ESCHERICHIA-COLI; NUCLEOTIDE-SEQUENCES; CATALYTIC ACTIVITIES; MOLECULAR-CLONING; PROTEIN-SYNTHESIS; GENE-EXPRESSION; CDNA CLONING AB A full-length cDNA clone encoding a novel form of the cytochrome P450 3A subfamily (Cyp3a-25) has been isolated from a mouse liver cDNA library. The sequence contained 2010 base pairs and encoded a protein with 503 amino acids. The amino acid sequence shared greater identities with rat CYP3A18 (90%) and golden hamster CYP3A10 (81%) sequences than with known mouse sequences (Cyp3a-11, Cyp3a-13, Cyp3a-16, and Cyp3a-41 [68-70%]). CYP3A25 was expressed in the Escherichia coli PCWori(+) expression vector following slight modifications of the N- and C-terminals of the cDNA. The purified CYP3A25 was recognized on an immunoblot by CYP3A1 antibody and has a molecular weight of 50 kD. CYP3A25 was catalytically active in the GP-hydroxylation of testosterone and the N-demethylation of benzphetamine and erythromycin. It was demonstrated by RT-PCR that the CYP3A25 mRNA is present in both fetal and adult tissues, including liver, lung; intestines, kidney, and brain. Northern blotting demonstrated that expression is greatest in the liver and small intestine. (C) 2001 John Wiley & Sons, Inc. C1 N Carolina State Univ, Dept Toxicol, Raleigh, NC 27695 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Coll Vet Med, Raleigh, NC 27695 USA. RP Rose, RL (reprint author), N Carolina State Univ, Dept Toxicol, POB 7633, Raleigh, NC 27695 USA. FU NIEHS NIH HHS [ES 00044] NR 48 TC 23 Z9 23 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2001 VL 15 IS 2 BP 90 EP 99 DI 10.1002/jbt.4 PG 10 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 419DU UT WOS:000167934700004 PM 11284050 ER PT J AU Walker, NJ AF Walker, NJ TI Real-time and quantitative PCR: Applications to mechanism-based toxicology SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article DE RT-PCR; toxicogenomics; gene expression profiling; molecular epidemiology; biological models; genetic techniques; microarrays; dose-response relationships; pharmacokinetics; DNA polymorphisms ID POLYMERASE-CHAIN-REACTION; MESSENGER-RNA EXPRESSION; RT-PCR; MOLECULAR BEACONS; GENE-EXPRESSION; DOSE-RESPONSE; PLASMID DNA; BLOOD; ASSAY; QUANTIFICATION AB There is increasing awareness that quantitative analysis of changes in molecular targets plays a key role in addressing scientific questions in molecular toxicology, molecular epidemiology, and human risk assessment. One of the emerging technologies that is being used to analyze these molecular targets is realtime and quantitative (RTAQ) polymerase chain reaction (PCR). The aim of this review is to provide the reader with an overview of this technology and to highlight specific applications of this technology to some key areas of molecular toxicology. (C) 2001 John Wiley & Sons, Inc. C1 NIEHS, Mol Epidemiol & Dosimetry Sect, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Walker, NJ (reprint author), NIEHS, Mol Epidemiol & Dosimetry Sect, Lab Computat Biol & Risk Anal, 111 Alexander Dr,POB 12233,MD D4-01, Res Triangle Pk, NC 27709 USA. RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 43 TC 73 Z9 96 U1 1 U2 6 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2001 VL 15 IS 3 BP 121 EP 127 DI 10.1002/jbt.8 PG 7 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 438GY UT WOS:000169046300001 PM 11424221 ER PT J AU Hamadeh, HK Bushel, P Paules, R Afshari, CA AF Hamadeh, HK Bushel, P Paules, R Afshari, CA TI Discovery in toxicology: Mediation by gene expression array technology SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Review DE toxicogenomics; genomics; toxicology; microarrays; cDNA; single nucleotide polymorphisms; pattern recognition; bioinformatics; gene expression; biomarkers ID RISK ASSESSMENT; OLIGONUCLEOTIDE ARRAYS; HUMAN-LYMPHOCYTES; DNA MICROARRAY; LUNG-CANCER; CELL-LINES; PHARMACOGENOMICS; IDENTIFICATION; PATTERNS; POLYMORPHISM AB Toxicogenomics is a term that represents the merging of toxicology with novel genomics techniques. Data generated in the new-age era of toxicology is relatively complex, requires new bioinformatics tools for adequate interpretation, and allows for the rapid generation of testable hypotheses. Hazard identification and risk assessment processes will advance from the use of genomics techniques, which will lead to greater understanding of mechanism(s) of action of toxicants, development of novel biomarkers of exposure and effect, and better identification of sensitive subpopulations. (C) 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:231-242, 2001. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Afshari, CA (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 74 TC 35 Z9 39 U1 1 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2001 VL 15 IS 5 BP 231 EP 242 DI 10.1002/jbt.10006 PG 12 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 488VE UT WOS:000171956100001 PM 11835620 ER PT J AU Bignone, FA AF Bignone, FA TI Structural complexity of early embryos: A study on the nematode Caenorhabditis elegans SO JOURNAL OF BIOLOGICAL PHYSICS LA English DT Article DE body plan; Caenorhabditis elegans; complexity; development; dynamical systems; gastrulation; genetic networks; protein folding ID CELL LINEAGE; EVOLUTION; ORDER AB For analytical studies on the dynamics of gene expression, gene expression control and cellular interactions, the nematode Caenorhabditis elegans [C. elegans] is at present one of the best suited models [1-4]. In this organism the genetic map and sequence is known [5], moreover the constancy of its lineage tree allows a complete description of cellular clones giving rise to embryos. These characteristics have fostered detailed studies on several aspects of development for this organism. Quantitative studies of cellular movement, through time lapse cinematography of gastrulation, allows the description of cellular migrations giving rise to the final embryonic structure. In perspective, these studies coupled with: genetic analysis, patterns of gene expression obtained through molecular techniques or other methods, open up the possibility of dynamical studies at the organismic scale. This possibility implies, first of all, a study of partitioning of space, and raise several problems in order to define basic conceptual tools to be used in such studies. One of the main problems to handle in this respect is the definition of embryonic structure in a quantitative way. We will show that this aspect is a more general case of distance geometry approaches, as defined in protein folding studies. In this paper we discuss measures of the complexity for embryonal body plans, at the end of grastrulation. These can be applied to studies on the dynamics of gene expression and phylogenetic studies with further experiments or simulations. C1 IST, Natl Canc Inst, Expt Oncol Lab, I-16123 Genoa, Italy. EM abignone@unige.it NR 31 TC 6 Z9 6 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0092-0606 EI 1573-0689 J9 J BIOL PHYS JI J. Biol. Phys. PY 2001 VL 27 IS 2-3 BP 257 EP 283 DI 10.1023/A:1013178514397 PG 27 WC Biophysics SC Biophysics GA 500CM UT WOS:000172608400013 PM 23345748 ER PT J AU MacGowan, GA Du, CW Glonty, V Suhan, JP Koretsky, AP Farkas, DL AF MacGowan, GA Du, CW Glonty, V Suhan, JP Koretsky, AP Farkas, DL TI Rhod-2 based measurements of intracellular calcium in the perfused mouse heart: Cellular and subcellular localization and response to positive inotropy SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE mouse heart; rhod-2; calcium; inotropy ID CYTOSOLIC CA2+; TRANSIENTS; QUANTITATION; INDO-1 AB We have demonstrated a method of measuring intracellular calcium in the perfused mouse heart with the red fluorescent dye rhod-2. In Langendorff perfused isolated mouse hearts, rhod-2 is bolused through the perfusate, resulting in a 6.2+/-1.9-fold increase in fluorescence over background, and calcium transients with a transient amplitude to diastolic fluorescence ratio of 33+/-9%. Quantification of the relative amount of rhod-2 in the heart was done by taking the ratio of absorbance at 524 nm (rhod-2 sensitive) to 589 nm (rhod-2 insensitive). Maximal calcium saturated fluorescence was measured during tetanization of the heart with calcium chloride (20 mM) and cyclopiazonic acid (10 muM). Electron microscopy was used to determine the subcellular localization of rhod-2, by fixing rhod-2 in the heart with a carbodiimide compound, and then using a double antibody technique to stain rhod-2. These images demonstrated prominent cytosolic rhod-2 localization. Fluorescence and confocal fluorescence microscopy were consistent with the electron microscopy data. Endothelial cell uptake of rhod-2 was shown with fluorescence microscopy, though functional studies with bradykinin infusion (3 muM), which increases endothelial cell calcium, had no effects on mean fluorescence (N = 4, p = NS), suggesting that endothelial uptake was small relative to total fluorescence. Calculated values of intracellular calcium were 686+/-237 nM at peak systole, and 360+/-101 nM in diastole, and with high perfusate calcium (3.5 mM) were 1199+/-215 and 544+/-53 nM, respectively. Thus, this appears a valid method of measuring cytosolic calcium in the perfused mouse heart, which will help determine the mechanisms of altered contractility in genetically engineered mice. (C) 2001 Society of Photo-Optical instrumentation Engineers. C1 Univ Pittsburgh, Med Ctr, Cardiovasc Inst, NMR Inst Biomed Res, Pittsburgh, PA 15213 USA. Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. Ctr Light Microscope Imaging & Biotechnol, Pittsburgh, PA 15213 USA. Carnegie Mellon Univ, Dept Biomed Sci, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Biol Engn, Pittsburgh, PA 15213 USA. Pittsburgh NMR Inst Biomed Res, Pittsburgh, PA 15213 USA. Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. NINDS, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Biomed Engn, Pittsburgh, PA 15213 USA. RP MacGowan, GA (reprint author), Univ Pittsburgh, Med Ctr, Cardiovasc Inst, NMR Inst Biomed Res, S550 Scaife Hall,200 Lothrop St, Pittsburgh, PA 15213 USA. RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU NHLBI NIH HHS [HL-03826, HL-02847, HL-40354] NR 18 TC 17 Z9 18 U1 0 U2 0 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JAN PY 2001 VL 6 IS 1 BP 23 EP 30 DI 10.1117/1.1316091 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 399GF UT WOS:000166802700003 PM 11178577 ER PT J AU Ishii, Y Markus, MA Tycko, R AF Ishii, Y Markus, MA Tycko, R TI Controlling residual dipolar couplings in high-resolution NMR of proteins by strain induced alignment in a gel SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE dipolar couplings; polyacrylamide gel; protein NMR; structure determination; weak alignment ID IMMUNOGLOBULIN-BINDING DOMAIN; LIQUID-CRYSTALLINE MEDIUM; MAGNETIC-FIELD; HUMAN UBIQUITIN; S4 DELTA-41; MACROMOLECULES; SPECTRA; SPECTROSCOPY; ORIENTATION; MOLECULES AB Water-soluble biological macromolecules can be weakly aligned by dissolution in a strained, hydrated gel such as cross-linked polyacrylamide, an effect termed `strain-induced alignment in a gel' (SAG). SAG induces nonzero nuclear magnetic dipole-dipole couplings that can be measured in high-resolution NMR spectra and used as structural constraints. The dependence of experimental N-15-H-1 dipolar couplings extracted from two-dimensional heteronuclear single quantum coherence (HSQC) spectra on several properties of compressed polyacrylamide, including the extent of compression, the polyacrylamide concentration, and the cross-link density, is reported for the B1 immunoglobulin binding domain of streptococcal protein G (protein G/B1, 57 residues). It is shown that the magnitude of macromolecular alignment can be widely varied by adjusting these properties, although the orientation and asymmetry of the alignment tensor are not affected significantly. The dependence of the N-15 relaxation times T-1 and T-2 of protein G/B1 on polyacrylamide concentration are also reported. In addition, the results of N-15 relaxation and HSQC experiments on the RNA binding domain of prokaryotic protein S4 from Bacillus stearothermophilus (S4 Delta 41, residues 43-200) in a compressed polyacrylamide gel are presented. These results demonstrate the applicability of SAG to proteins of higher molecular weight and greater complexity. A modified in-phase/anti-phase (IPAP) HSQC technique is described that suppresses natural-abundance N-15 background signals from amide groups in polyacrylamide, resulting in cleaner HSQC spectra in SAG experiments. The mechanism of protein alignment in strained polyacrylamide gels is contrasted with that in liquid crystalline media. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Struct Mol Biol Unit, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RI Ishii, Yoshitaka/F-4558-2014 OI Ishii, Yoshitaka/0000-0002-7724-6469 NR 43 TC 80 Z9 81 U1 0 U2 11 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PY 2001 VL 21 IS 2 BP 141 EP 151 DI 10.1023/A:1012417721455 PG 11 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 481TJ UT WOS:000171536000006 PM 11727977 ER PT J AU Ishima, R Louis, JM Torchia, DA AF Ishima, R Louis, JM Torchia, DA TI Optimized labeling of (CHD2)-C-13 methyl isotopomers in perdeuterated proteins: Potential advantages for C-13 relaxation studies of methyl dynamics of larger proteins SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE conformational change; internal motion; isotope labeling; model-free; NMR ID H-2-LABELED PROTEINS; HIV-1 PROTEASE; SIDE-CHAINS; TIMES AB (CHD2)-C-13 methyl isotopomers are particularly useful to study methyl dynamics in proteins because, as compared with other methyl isotopomers, the C-13 relaxation mechanism for this isotopomer is straightforward. However, in the case of proteins, where (omega tau)(2) > 1, the refocused INEPT pulse sequence does not completely suppress unwanted (CH3)-C-13 signals. The presence of weak (CH3)-C-13 peaks is usually not a serious problem for smaller proteins because there are relatively few methyl signals and they are sharp; however, signal overlap becomes more common as the size of the protein increases. We overcome this problem by preparing a protein using a 98% D2O cell culture medium containing 3-C-13 pyruvic acid, 50-60% deuterated at the 3-position, and 4-C-13 2-ketobutyric acid, 98% and 62% deuterated at the 3- and 4-positions, respectively. This approach significantly reduces the population of the CH3 isotopomer while optimizing the production of (CHD2)-C-13, the isotopomer desired for C-13 relaxation measurements. In larger proteins where the deuterium T-2 may be too short to measure accurately, we also suggest the alternative measurement of the proton T-2 of the (CH2D)-C-13 methyl isotopomer, because these protons are well-isolated from other protons in these highly deuterated samples. C1 Natl Inst Dent & Craniofacial Res, Struct Mol Biol Unit, NIH, Bethesda, MD 20892 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Torchia, DA (reprint author), Natl Inst Dent & Craniofacial Res, Struct Mol Biol Unit, NIH, Bethesda, MD 20892 USA. NR 16 TC 20 Z9 20 U1 0 U2 7 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PY 2001 VL 21 IS 2 BP 167 EP 171 DI 10.1023/A:1012482426306 PG 5 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 481TJ UT WOS:000171536000009 PM 11727980 ER PT J AU Gruschus, JM Ferretti, JA AF Gruschus, JM Ferretti, JA TI Quantitative measurement of water diffusion lifetimes at a protein/DNA interface by NMR SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE B-factors; binding specificity and affinity; conserved water; cross-relaxation; homeodomain; hydrogen bond; relay magnetization transfer; ROE and NOE; temperature factors; water residence time; X-ray ID HOMEODOMAIN-DNA COMPLEX; VND/NK-2 HOMEODOMAIN; CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; HYDRATION WATER; SPECTROSCOPY; MOLECULES; DYNAMICS; HELIX; MACROMOLECULES AB Hydration site lifetimes of slowly diffusing water molecules at the protein/DNA interface of the vnd/NK-2 homeodomain DNA complex were determined using novel three-dimensional NMR techniques. The lifetimes were calculated using the ratios of ROE and NOE cross-relaxation rates between the water and the protein backbone and side chain amides. This calculation of the lifetimes is based on a model of the spectral density function of the water-protein interaction consisting of three timescales of motion: fast vibrational/rotational motion, diffusion into/out of the hydration site, and overall macromolecular tumbling. The lifetimes measured ranged from approximately 400 ps to more than 5 ns, and nearly all the slowly diffusing water molecules detected lie at the protein/DNA interface. A quantitative analysis of relayed water cross-relaxation indicated that even at very short mixing times, 5 ms for ROESY and 12 ms for NOESY, relay of magnetization can make a small but detectable contribution to the measured rates. The temperature dependences of the NOE rates were measured to help discriminate direct dipolar cross-relaxation from chemical exchange. Comparison with several X-ray structures of homeodomain/DNA complexes reveals a strong correspondence between water molecules in conserved locations and the slowly diffusing water molecules detected by NMR. A homology model based on the X-ray structures was created to visualize the conserved water molecules detected at the vnd/NK-2 homeodomain DNA interface. Two chains of water molecules are seen at the right and left sides of the major groove, adjacent to the third helix of the homeodomain. Two water-mediated hydrogen bond bridges spanning the protein/DNA interface are present in the model, one between the backbone of Phe8 and a DNA phosphate, and one between the side chain of Asn51 and a DNA phosphate. The hydrogen bond bridge between Asn51 and the DNA might be especially important since the DNA contact made by the invariant Asn51 residue, seen in all known homeodomain/DNA structures, is critical for binding affinity and specificity. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Ferretti, JA (reprint author), NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NR 36 TC 14 Z9 14 U1 0 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PY 2001 VL 20 IS 2 BP 111 EP 126 DI 10.1023/A:1011266703693 PG 16 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 443FW UT WOS:000169331000002 PM 11495243 ER PT J AU de Alba, E Suzuki, M Tjandra, N AF de Alba, E Suzuki, M Tjandra, N TI Simple multidimensional NMR experiments to obtain different types of one-bond dipolar couplings simultaneously SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE Bax; dipolar couplings; liquid crystal; protein structure ID MACROMOLECULES; PROTEINS AB In order to measure residual dipolar couplings, the molecule under study has to be partially oriented in the presence of the magnetic field. It has been observed that some protein samples are not stable under the conditions imposed by the orienting media. If different types of dipolar couplings are measured sequentially, their values will not agree with a unique alignment tensor that is changing slowly over time. This could bias the structure calculation. It would be more appropriate to obtain different types of dipolar couplings simultaneously, such that all the data correspond to one effective alignment tensor. We describe here a general NMR strategy designed to do so, that can be adapted to various existing pulse sequences. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Tjandra, N (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 3, Bethesda, MD 20892 USA. NR 10 TC 13 Z9 14 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD JAN PY 2001 VL 19 IS 1 BP 63 EP 67 DI 10.1023/A:1008341128327 PG 5 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 396EV UT WOS:000166624100006 PM 11246855 ER PT J AU Eisenmesser, EZ Horita, DA Byrd, RA AF Eisenmesser, EZ Horita, DA Byrd, RA TI Secondary structure and backbone resonance assignments for human interleukin-13 SO JOURNAL OF BIOMOLECULAR NMR LA English DT Letter DE chemical shift index; IL-13; interleukin-13; secondary structure C1 NCI, Macromol NMR Sect, Struct Biophys Lab, Frederick, MD 21702 USA. RP Byrd, RA (reprint author), NCI, Macromol NMR Sect, Struct Biophys Lab, POB B,Bldg 538, Frederick, MD 21702 USA. RI Byrd, R. Andrew/F-8042-2015 OI Byrd, R. Andrew/0000-0003-3625-4232 NR 10 TC 5 Z9 5 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD JAN PY 2001 VL 19 IS 1 BP 93 EP 94 DI 10.1023/A:1008336103603 PG 2 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 396EV UT WOS:000166624100016 PM 11246865 ER PT J AU Cui, L Ma, YF Yao, W Zhou, H Setterberg, RB Liang, TC Jee, WSS AF Cui, L Ma, YF Yao, W Zhou, H Setterberg, RB Liang, TC Jee, WSS TI Cancellous bone of aged rats maintains its capacity to respond vigorously to the anabolic effects of prostaglandin E-2 by modeling-dependent bone gain SO JOURNAL OF BONE AND MINERAL METABOLISM LA English DT Article DE prostaglandin E-2; aged male rats; proximal tibial metaphyses; modeling; remodeling ID TRABECULAR BONE; MURINE MODEL; ADULT-RATS; MARROW; CELLS; MASS; OSTEOPOROSIS; GROWTH; OSTEOBLASTOGENESIS; HISTOMORPHOMETRY AB The present study examined the early effects of prostaglandin (PG)E-2 on proximal tibial metaphyses of 20-month-old Wistar male rats. PGE(2) was given to intact rats for 10 and 30 days at 3 mg/kg/day. After multiple in vivo fluorochrome labeling, undecalcified longitudinal sections were subjected to analysis of bone histomorphometry and classification of the contour of the cement line in bone formation units. The latter was used to classify bone formation units into modeling, remodeling and uncertain units. After 10 days of treatment, there was a 2% increase in woven bone formation with the appearance of osteoprogenitor cells and increases in the number of osteoblasts (649%) and osteoid (375%) surfaces. Remodeling and modeling units increased by 56% and 429%, respectively. After 30 days of treatment, there was an increase of 212% of total trabecular bone mass, 60% of which was woven bone. In addition, there were increases in labeling surface (147%), mineral apposition rate (760%), bone formation rates tissue area (BFR/T.Ar, 1920%; BFR/B.Pm, 343%), and bone turnover (BFR/B.Ar, 426%). Osteoblasts and osteoid production at 30 days were 29% and 58% less than at 10 days post-treatment. Modeling and remodeling activity did not differ from that seen at 10 days. In addition, PGE, treatment tended to stimulate the closing of growth plates and decrease the fatty marrow area. We conclude that the aged skeleton was able to respond vigorously to PGE, treatment. Massive osteoprogenitors cells, and osteoid and osteoblast formations were observed within 10 days, and dramatic woven and lamellar bone formation was seen at 30 days post-treatment. The anabolic effects were driven mainly by modeling. C1 Univ Utah, Div Radiobiol, Salt Lake City, UT 84108 USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Jee, WSS (reprint author), Univ Utah, Div Radiobiol, 729 Arapeen,Suite 2334, Salt Lake City, UT 84108 USA. NR 46 TC 22 Z9 24 U1 1 U2 1 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113, JAPAN SN 0914-8779 J9 J BONE MINER METAB JI J. Bone Miner. Metab. PY 2001 VL 19 IS 1 BP 29 EP 37 DI 10.1007/s007740170057 PG 9 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA 386MN UT WOS:000166066100006 PM 11156470 ER PT J AU Pozsgay, V AF Pozsgay, V TI Large scale synthesis of 2-azidodeoxy glucosyl donors SO JOURNAL OF CARBOHYDRATE CHEMISTRY LA English DT Article ID SHIGELLA-DYSENTERIAE TYPE-1; NUCLEAR-MAGNETIC-RESONANCE; O-SPECIFIC POLYSACCHARIDE; OLIGOSACCHARIDE SYNTHESIS; BUILDING-BLOCKS; AZIDONITRATION; DERIVATIVES; PRECURSORS; FRAGMENT; ROUTE AB Starting from readily available phenyl 1-thio-beta -D-mannopyranoside, phenyl 2-azido-2-deoxy-1-thio-beta -D-glucopyranoside (9) was synthesized on multigram scale using inexpensive reagents. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Pozsgay, V (reprint author), NICHHD, NIH, 6 Ctr Dr,MSC 2720, Bethesda, MD 20892 USA. NR 16 TC 4 Z9 4 U1 1 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0732-8303 J9 J CARBOHYD CHEM JI J. Carbohydr. Chem. PY 2001 VL 20 IS 7-8 BP 659 EP 665 DI 10.1081/CAR-100108280 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 505MK UT WOS:000172916400012 ER PT J AU Chan, SK Jaffer, FA Botnar, RM Kissinger, KV Goepfert, L Chuang, ML O'Donnell, CJ Levy, D Manning, WJ AF Chan, SK Jaffer, FA Botnar, RM Kissinger, KV Goepfert, L Chuang, ML O'Donnell, CJ Levy, D Manning, WJ TI Scan reproducibility of magnetic resonance imaging assessment of aortic atherosclerosis burden SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE aorta; atherosclerosis; magnetic resonance imaging; subclinical disease ID CORONARY-ARTERY DISEASE; IN-VIVO; MYOCARDIAL-INFARCTION; PLAQUE; COMPONENTS AB Subclinical atherosclerosis precedes the onset of clinical disease by many years. Noninvasive magnetic resonance imaging (MRI) offers the opportunity to visualize and quantify atherosclerotic plaque. However, the reproducibility of MRI measurements of abdominal and thoracic aortic atherosclerosis has not been reported. Electrocardiogram-gated, T2-weighted, turbo spin echo MRI of the descending thoracic and abdominal aorta was performed on 16 subjects, comprising 10 subjects with multivessel coronary artery disease (CAD) and 6 subjects without angiographic CAD. Three identical MRIs were performed on each subject, with subject repositioning between the second and third scans. Aortic anatomic and plaque measurements were performed in a blinded fashion. Fourteen subjects (88%) had MRI evidence of atherosclerotic plaque on at least one image. Slice plaque burden, plaque area, and plaque perimeter were greater in the CAD group (52% vs. 9%, p = 0.002: 264 vs. 18 mm(2), p = 0.009; 159 vs. 15 mm, p = 0.006, respectively). Measurements of total aortic lumen area, lumen circumference, plaque area, and plaque perimeter correlated highly among the three scans (all r = 0.96, all p < 0.001). Measurements of slice-specific is aortic lumen area and lumen circumference also correlated highly (all r = 0.98, all p < 0.001). Correlations of slice-specific plaque area and plaque perimeter were significant (all p < 0.001) but less robust (r = 0.62-0.85). These data demonstrate that MRI is a reproducible technique for assessing aortic anatomy and total aortic atherosclerosis, but increased slice density should be considered if serial evaluation of slice-specific data is desired. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Harvard Thorndike Lab, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Harvard Thorndike Lab, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Philips Med Syst RMB, Best, Netherlands. Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. RP Manning, WJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Harvard Thorndike Lab, Boston, MA 02215 USA. RI Botnar, Rene/E-6875-2012; OI Botnar, Rene/0000-0003-2811-2509; Jaffer, Farouc/0000-0001-7980-384X NR 18 TC 37 Z9 37 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1097-6647 J9 J CARDIOV MAGN RESON JI J. Cardiov. Magn. Reson. PY 2001 VL 3 IS 4 BP 331 EP 338 DI 10.1081/JCMR-100108587 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 505KE UT WOS:000172911300007 PM 11777225 ER PT J AU Zhao, XH Greener, T Al-Hasani, H Cushman, SW Eisenberg, E Greene, LE AF Zhao, XH Greener, T Al-Hasani, H Cushman, SW Eisenberg, E Greene, LE TI Expression of auxilin or AP180 inhibits endocytosis by mislocalizing clathrin: evidence for formation of nascent pits containing AP1 or AP2 but not clathrin SO JOURNAL OF CELL SCIENCE LA English DT Article DE auxilin; AP180; endocytosis ID RECEPTOR-MEDIATED ENDOCYTOSIS; SYNAPTIC VESICLE ENDOCYTOSIS; GLUCOSE-TRANSPORTER GLUT4; COATED VESICLES; PROTEIN COMPLEX; BINDING-PROTEIN; 3T3-L1 ADIPOCYTES; GOLGI MEMBRANES; BREFELDIN-A; DYNAMIN AB Although uncoating of clathrin-coated vesicles is a key event in clathrin-mediated endocytosis it is unclear what prevents uncoating of clathrin-coated pits before they pinch off to become clathrin-coated vesicles. We have shown that the J-domain proteins auxilin and GAK are required for uncoating by Hsc70 in vitro. In the present study, we expressed auxilin in cultured cells to determine if this would block endocytosis by causing premature uncoating of clathrin-coated pits. We found that expression of auxilin indeed inhibited endocytosis. However, expression of auxilin with its J-domain mutated so that it no longer interacted with Hsc70 also inhibited endocytosis as did expression of the clathrin-assembly protein, AP180, or its clathrin-binding domain. Accompanying this inhibition, we observed a marked decrease in clathrin associated with the plasma membrane and the trans-Golgi network, which provided us with an opportunity to determine whether the absence of clathrin from clathrin-coated pits affected the distribution of the clathrin assembly proteins AP1 and AP2. Surprisingly we found almost no change in the association of AP2 and AP1 with the plasma membrane and the trans-Golgi network, respectively. This was particularly obvious when auxilin or GAK was expressed with functional J-domains since, in these cases, almost all of the clathrin was sequestered in granules that also contained Hsc70 and auxilin or GAK, We conclude that expression of clathrin-binding proteins inhibits clathrin-mediated endocytosis by sequestering clathrin so that it is no longer available to bind to nascent pits but that assembly proteins bind to these pits independently of clathrin. C1 NHLBI, Cell Biol Lab, Bethesda, MD 20892 USA. NIDDK, Expt Diabet Metab & Nutr Sect, NIH, Bethesda, MD USA. RP Greene, LE (reprint author), NHLBI, Cell Biol Lab, Bethesda, MD 20892 USA. NR 63 TC 71 Z9 71 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JAN PY 2001 VL 114 IS 2 BP 353 EP 365 PG 13 WC Cell Biology SC Cell Biology GA 400NG UT WOS:000166877600012 PM 11148137 ER PT J AU Yarden, RI Brody, LC AF Yarden, RI Brody, LC TI Identification of proteins that interact with BRCA1 by Far-Western library screening SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE BRCA1; BRCT domain; retinoblastoma-binding protein; RbAp46; breast cancer; proteomics; protein-protein interactions; ribosomal protein L31; DNA repair ID SUSCEPTIBILITY GENE BRCA1; DNA-DAMAGE; OVARIAN-CANCER; TRANSCRIPTIONAL ACTIVITY; BINDING PROTEIN; EXPRESSION; BREAST; CLONING; MUTATIONS; COMPLEX AB Protein-protein interactions control numerous biological processes. In the case of a protein with no known function, identification of interacting proteins may lend insight into its cellular function. Protein-protein interactions are often detected by yeast two-hybrid screening which is based on a transcriptional read-out. One limitation of this technique is that transcription factors, when used as bait, frequently impair the effectiveness of this screen because they give rise to high levels of false positives. The carboxyl terminus of the breast cancer tumor suppressor gene, BRCA1, contains two BRCT motifs, a motif found in several DNA repair and cell cycle checkpoint proteins. This region of BRCA1 also exhibits an intrinsic transcriptional transactivation activity when bound to DNA as a fusion protein, thereby limiting its use in yeast two-hybrid screen. In order to isolate proteins that interact with this domain of BRCA1, we utilized a Far-Western screen, a method based on direct protein binding. We used recombinant histidine-tagged BRCT as the primary protein probe. We isolated eight cDNAs that bind to the BRCT domain of BRCA1. Further analysis demonstrated that two of the clones encode for proteins that interact directly with the BRCT domain of BRCA1. (C) 2001 Wiley-Liss, Inc. C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Brody, LC (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Room 3A14, Bethesda, MD 20892 USA. NR 31 TC 3 Z9 5 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2001 VL 83 IS 4 BP 521 EP 531 DI 10.1002/jcb.1257 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 488KG UT WOS:000171933900001 PM 11746496 ER PT J AU Horikawa, I Parker, ES Solomon, GG Barrett, JC AF Horikawa, I Parker, ES Solomon, GG Barrett, JC TI Upregulation of the gene encoding a cytoplasmic dynein intermediate chain in senescent human cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE cDNA subtraction; cellular senescence; cytoplasmic dynein; molecular motor; chromosome 7q ID CELLULAR SENESCENCE; HUMAN FIBROBLASTS; GROWTH ARREST; TELOMERASE; EXPRESSION; SEQUENCES; CANCER; COMPLEMENTATION; IDENTIFICATION; CHROMOSOME-7 AB Normal human somatic cells, unlike cancer cells, stop dividing after a limited number of cell divisions through the process termed cellular senescence or replicative senescence, which functions as a tumor-suppressive mechanism and may be related to organismal aging. By means of the cDNA subtractive hybridization, we identified eight genes upregulated during normal chromosome 3-induced cellular senescence in a human renal cell carcinoma cell line. Among them is the DNCl1 gene encoding an intermediate chain 1 of the cytoplasmic dynein, a microtubule motor that plays a role in chromosome movement and organelle transport. The DNCl1 mRNA was also upregulated during in vitro aging of primary human fibroblasts. In contrast, other components of cytoplasmic dynein showed no significant change in mRNA expression during cellular aging. Cell growth arrest by serum starvation, contact inhibition, or gamma -irradiation did not induce the DNCl1 mRNA, suggesting its specific role in cellular senescence. The DNCl1 gene is on the long arm of chromosome 7 where tumor suppressor genes and a senescence-inducing gene for a group of immortal cell lines (complementation group D) are mapped. This is the first report that links a component of molecular motor complex to cellular senescence, providing a new insight into molecular mechanisms of cellular senescence. (C) 2001 Wiley-Liss, Inc. C1 NCI, Canc & Aging Sect, Lab Biosyst & Canc, Bethesda, MD 20892 USA. Natl Inst Environm Hlth Sci, Lab Mol Carcinogenesis, Res Triangle Pk, NC 27709 USA. RP Horikawa, I (reprint author), NCI, Canc & Aging Sect, Lab Biosyst & Canc, 9000 Rockville Pike,Bldg 40 Rm 2609, Bethesda, MD 20892 USA. NR 30 TC 11 Z9 11 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2001 VL 82 IS 3 BP 415 EP 421 DI 10.1002/jcb.1169 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 458QN UT WOS:000170206200006 PM 11500918 ER PT J AU McInerney, JM Wilson, MA Strand, KJ Chrysogelos, SA AF McInerney, JM Wilson, MA Strand, KJ Chrysogelos, SA TI A strong intronic enhancer element of the EGFR gene is preferentially active in high EGFR expressing breast cancer cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE epidermal growth factor receptor; intron; cis-acting element; gene expression; breast cancer ID GROWTH-FACTOR RECEPTOR; GEL-ELECTROPHORESIS; ESTROGEN-RECEPTOR; MESSENGER-RNAS; PROMOTER; BINDING; TRANSCRIPTION; SEQUENCE; LINES; IDENTIFICATION AB Hormone-independent human breast cancer is characterized by estrogen receptor (ER) loss and the acquisition of high epidermal growth factor receptor (EGFR) levels. Despite the tendency for an inverse correlation between EGFR and ER, EGFR is a strong prognostic indicator for poor survival rate independent of ER status suggesting that EGFR overexpression is an important step in the progression to estrogen independence. We have previously shown that several DNase I hypersensitive sites which correspond to potential regulatory regions reside within the EGFR gene first intron exclusively in hormone-independent breast cancer cells. CAT assays investigating the transcriptional activity of the first intron of EGFR indicate that a 140 bp region has an enhancer ability specifically in these hormone-independent breast cancer cells. The DNA-protein interaction that occurs in this enhancer was localized to a 35 bp region and displayed enhancer-like activity in the same hormone-independent breast cancer cells. Furthermore, the protein that binds to this 35 bp region seems to be ubiquitous in the cell lines tested but in higher abundance in high EGFR expressing cells. identifying the specific regulatory elements involved in EGFR up-regulation could lead to the development of therapies for preventing and treating estrogen-independent breast cancer. J. Cell. Biochem. 80:538-549, 2001. (C) 2001 Wiley-Liss, Inc. C1 Dartmouth Coll, Sch Med, Dept Med, Hanover, NH 03755 USA. Dartmouth Coll, Sch Med, Dept Pharmacol, Hanover, NH 03755 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. RP McInerney, JM (reprint author), Dartmouth Coll, Sch Med, Dept Med, HB 7650, Hanover, NH 03755 USA. FU NCI NIH HHS [2P30-CA51008, CA55677] NR 37 TC 24 Z9 24 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2001 VL 80 IS 4 BP 538 EP 549 DI 10.1002/1097-4644(20010315)80:4<538::AID-JCB1008>3.0.CO;2-2 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 398KA UT WOS:000166754600009 PM 11169738 ER PT J AU Bubunenko, M King, ML AF Bubunenko, M King, ML TI Biochemical characterization of a cellular structure retaining vegetally localized RNAs in Xenopus late stage oocytes SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE RNA localization; Xenopus oocytes; cytoskeleton; RNA-binding proteins; cortical retention of localized RNPs ID GERM PLASM COMPONENT; MESSENGER-RNA; BINDING-PROTEIN; VG1 RNA; CORTEX; EMBRYOS; DROSOPHILA; OOGENESIS; PATHWAY; TRANSLATION AB Two pathways operate during Xenopus oogenesis to localize a small number of RNAs to the vegetal cortex. Correct localization of these RNAs is essential to normal development as the proteins they encode are involved in specifying cell type and in patterning the early embryo. Binding these RNAs to the vegetal cortex and thus preserving their localized condition is a critical step, although little is known about how this is achieved. In this study, we have used a biochemical approach to examine the anchoring step. Xlsirts, an abundant localized RNA (locRNA), was selectively enriched in a detergent-insoluble fraction (DIF) prepared from oocytes that had completed the RNA localization process. These putative RNA-anchoring complexes were analyzed by density gradient centrifugation and in RNA-protein binding assays. Cortical Xlsirts and other localized RNAs are specifically found in the heavy region of sucrose gradients and in the pellet, quite different from other cellular RNPs. Four proteins were identified by UV-crosslinking that bound the Xlsirts localization signal in the carter, but not in the soluble fraction. These are likely members of the anchoring complex and appear to include vera, a characterized Vg1 RNA binding protein. Vera was found to co-sediment with other locRNAs found in the vegetal cortex, suggesting that it is a common component of locRNPs. Finally, we found that locRNPs extracted into the soluble fraction had the same buoyant density as typical ooplasmic RNPs. We propose that locRNAs are organized and anchored in the cortex as typical RNPs. J. Cell. Biochem. 80:560-570, 2001. (C) 2001 Wiley-Liss, Inc. C1 Univ Miami, Sch Med, Dept Cell Biol & Anat, Miami, FL 33136 USA. NIH, Bethesda, MD 20892 USA. RP King, ML (reprint author), Univ Miami, Sch Med, Dept Cell Biol & Anat, 1011 NW 15th St, Miami, FL 33136 USA. NR 42 TC 5 Z9 5 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2001 VL 80 IS 4 BP 560 EP 570 DI 10.1002/1097-4644(20010315)80:4<560::AID-JCB1010>3.0.CO;2-O PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 398KA UT WOS:000166754600011 PM 11169740 ER PT J AU Nacken, W Lekstrom-Himes, JA Sorg, C Manitz, MP AF Nacken, W Lekstrom-Himes, JA Sorg, C Manitz, MP TI Molecular analysis of the mouse S100A9 gene and evidence that the myeloid specific transcription factor C/EBPepsilon is not required for the regulation of the S100A9/A8 gene expression in neutrophils SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE S100A9; MRP14; calgranulin; S100 proteins; C/EBPepsilon; myeloid cells ID CALCIUM-BINDING PROTEINS; GRANULOCYTIC DIFFERENTIATION; MRP14 S100A9; C/EBP-ALPHA; EPSILON; FAMILY AB The genomic locus of the mouse S100A9 (MRP14) gene, a myeloid expressed gene belonging to the S100 family, is split in three exons and two introns. Insertions of B1 like and LINE elements as well as several sequence repeat structures are scattered over the gene suggesting that this region of the S100 gene cluster has been the subject of a high mutational activity in mouse evolution. The insertions may represent molecular footprints of a recently postulated inversion event, which resulted in a rearrangement of the S100 gene cluster in mouse compared to man. Deletion analysis of the promoter reveals, that a 1200 bp fragment is able to direct a cell type-specific expression of a reporter gene in granulocytic 32D cells. Unexpectedly, the myeloid-specific transcription factor C/EBPepsilon is not needed for the transcriptional upregulation of the S100A9 and S100A8 genes in neutrophils. The data described here provide further insights into the evolution of the S100 gene cluster and into the myeloid-specific regulation of the murine S100A9 gene expression. J. Cell. Biochem. 80:606-616, 2001. (C) 2001 Wiley-Liss, Inc. C1 Univ Munster, Inst Expt Dermatol, D-48149 Munster, Germany. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Nacken, W (reprint author), Univ Munster, Inst Expt Dermatol, Esmarch Str 56, D-48149 Munster, Germany. NR 23 TC 13 Z9 14 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2001 VL 80 IS 4 BP 606 EP 616 DI 10.1002/1097-4644(20010315)80:4<606::AID-JCB1015>3.0.CO;2-K PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 398KA UT WOS:000166754600016 PM 11169745 ER PT J AU Sekiya, I Koopman, P Tsuji, K Mertin, S Harley, V Yamada, Y Shinomiya, K Niguji, A Noda, M AF Sekiya, I Koopman, P Tsuji, K Mertin, S Harley, V Yamada, Y Shinomiya, K Niguji, A Noda, M TI Transcriptional suppression of Sox9 expression in chondrocytes by retinoic acid SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE SOX9; chondrocyte; retinoic acid; transcription; type II collagen ID AUTOSOMAL SEX REVERSAL; SRY-RELATED GENE; SENSITIVE PROTEIN GENE; CAMPOMELIC DYSPLASIA; II COLLAGEN; FACTOR AP-2; TRANSGENIC MICE; MOUSE; DNA; CHONDROGENESIS AB SOX9 is a transcription factor that is expressed in chondrocytes and regulates expression of chondrocyte phenotype related genes. Expression of these genes is known to be suppressed by retinoic acid (RA). We, therefore, examined whether the Sox9 gene expression is regulated by RA in chondrocytes. RA treatment suppressed Sox9 mRNA expression in primary chondrocytes prepared from newborn mouse rib cartilage within 12 h and this suppression lasted at least up to 24 h. The RA suppression of Sox9 mRNA levels was dose-dependent starting at 0.5 muM with a maximum at 1 muM. Nuclear run-on assays revealed that RA reduced the rate of transcription of Sox9 gene. Finally, Western blot analysis indicated that RA suppressed SOX9 protein revels in these chondrocytes. Furthermore, overexpression of SOX9 reversed RA suppression of Col/2a1 enhancer activity. These observations indicate that RA suppresses Sox9 gene expression in chondrocytes at least in part through transcriptional events. (C) 2001 Wiley-Liss, Inc. C1 Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pharmacol, Chiyoda Ku, Tokyo 101, Japan. Univ Queensland, Ctr Mol & Cellular Biol, Brisbane, Qld, Australia. Univ Melbourne, Howard Florey Inst Expt Physiol & Med, Parkville, Vic 3052, Australia. NIDR, Dev Biol Lab, Bethesda, MD 20892 USA. Natl Inst Craniofacial Res, Dev Biol Lab, Bethesda, MD 20892 USA. Tokyo Med & Dent Univ, Dept Orthopaed Surg, Tokyo, Japan. RP Noda, M (reprint author), Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pharmacol, Chiyoda Ku, 2-3-10 Kanda Surugadai, Tokyo 101, Japan. RI Koopman, Peter /C-9416-2009; OI Koopman, Peter /0000-0001-6939-0914; Harley, Vincent/0000-0002-2405-1262 NR 38 TC 6 Z9 6 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2001 SU 36 BP 71 EP 78 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 429XN UT WOS:000168543400008 ER PT J AU Yarden, RI Wilson, MA Chrysogelos, SA AF Yarden, RI Wilson, MA Chrysogelos, SA TI Estrogen suppression of EGFR expression in breast cancer cells: A possible mechanism to modulate growth SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE EGF receptor; estrogen; estrogen receptor; EGF; TGF-alpha; anti-estrogens; breast cancer cells; cell proliferation; apoptosis ID FACTOR RECEPTOR GENE; MESSENGER RIBONUCLEIC-ACID; FACTOR-ALPHA; GLUCOCORTICOID RECEPTOR; TRANSCRIPTIONAL ACTIVATION; PROGESTERONE RECEPTORS; NUCLEAR RECEPTORS; LACTOFERRIN GENE; PHORBOL ESTER; MICE LACKING AB Epidermal growth factor receptor (EGFR) is a transmembrane receptor whose overexpression in breast cancer predicts for poor prognosis and is inversely correlated with expression of estrogen receptor (ER). This study was designed to investigate whether estrogen plays an active role in suppression of EGFR expression in estrogen-responsive breast cancer cell lines expressing low levels of EGFR. Upon withdrawal of estrogen, EGFR mRNA and protein increased 3-6 fold in MCF-7, T47D, and BT474 ER+ breast cancer cells. This was reversible upon addition of estradiol back to the culture media, but only after prolonged treatment. Nuclear run-on assays and studies with the transcription inhibitor actinomycin B demonstrated that regulation is at the transcriptional level. These results indicate that in the presence of estrogen, ER+ breast cancer cells possess active mechanisms to suppress EGFR expression. Up-regulation of EGFR in response to estrogen depletion and growth inhibition could represent an attempt to rescue cell growth by utilizing an alternative pathway. Indeed, we found that estrogen-depleted breast cancer cells are more sensitive to the mitogenic effects of EGF and TGF-alpha, and simultaneous blockade of both estrogen and EG FR signaling pathways induced cell death. (C) 2001 Wiley-Liss, Inc. C1 Georgetown Univ, Dept Oncol, Washington, DC 20007 USA. RP Yarden, RI (reprint author), NHGRI, NIH, Rm 3A35 Bldg 49,49 Convent Dr, Bethesda, MD 20892 USA. NR 57 TC 33 Z9 34 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2001 SU 36 BP 232 EP 246 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 429XN UT WOS:000168543400024 ER PT J AU DeCristofaro, MF Betz, BL Rorie, CJ Reisman, DN Wang, WD Weissman, BE AF DeCristofaro, MF Betz, BL Rorie, CJ Reisman, DN Wang, WD Weissman, BE TI Characterization of SWI/SNF protein expression in human breast cancer cell lines and other malignancies SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID RETINOBLASTOMA GENE; TRANSCRIPTIONAL ACTIVATION; GROWTH ARREST; HUMAN HOMOLOG; GERM-LINE; COMPLEX; TUMORS; HETEROZYGOSITY; YEAST; DNA AB Organization of genomic DNA into chromatin aids in the regulation of gene expression by limiting access to transcriptional machinery. The SWI/SNF family of complexes, which are conserved from yeast to humans, are ATP-dependent chromatin-remodeling enzymes required for the transcription of a number of genes in yeast. In humans, the gene encoding the BAF47/hSNF5 subunit of the complex, located at 22q11.2, has been found to be mutated in a number of human tumors including rhabdoid, rhabdomyosarcoma, chronic myeloid leukemia, and CNS tumors such as medulloblastomas and choroid plexus carcinomas. in addition, loss of heterozygosity (LOH) has been reported for the BAF47 region in breast and liver cancer. LOH has also been reported in breast and ovarian cancer within 17q12-25, a gene-rich area including BRCA1, BAF60B, and BAF57. Interestingly, the gene encoding the BAF155/hSWI3 subunit of the complex maps to 3p21-p23, an area of chromosomal deletion seen in a number of human adenocarcinomas including breast, kidney, pancreas, and ovary. To look for abnormalities in these proteins as well as the SWI/SNF complex in general, we have determined the protein status of core human SWI/SNF components BAF170, BAF155, BAF57, BAF53a, and BAF47 in 22 breast cell lines. The complex status in other human tumor cell lines of various tissue types was also examined. We also determined the protein status of the human SW12 homologues, hBRM/SWI2 alpha and BRG1/SWI2 beta as well as two Other proteins found in human SWI/SNF complexes, BAF180 and BAF250. In this study, we identified the first cell line negative for the BAF57 protein as well as a pancreatic carcinoma cell line negative for both the BRG-1 and hBRM proteins, J. Cell. Physiol. 186:136-745, 2001. (C) 2001 Wiley-Liss, Inc. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC USA. NIA, Genet Lab, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Weissman, BE (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, CB 7295,Rm 32-062, Chapel Hill, NC 27599 USA. FU NCI NIH HHS [CA63176, 5-T32-CA71341-01]; NIEHS NIH HHS [5-T32-ES07017] NR 60 TC 123 Z9 127 U1 1 U2 11 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JAN PY 2001 VL 186 IS 1 BP 136 EP 145 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 379MF UT WOS:000165645300015 PM 11147808 ER PT J AU Chen, Y Ginis, I Hallenbeck, JM AF Chen, Y Ginis, I Hallenbeck, JM TI The protective effect of ceramide in immature rat brain hypoxia-ischemia involves up-regulation of Bcl-2 and reduction of TUNEL-positive cells SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE apoptosis; Bcl-2; ceramide; hypoxia; ischemia; neonatal rat ID NERVOUS-SYSTEM; TNF-ALPHA; DEATH; NEURONS; APOPTOSIS; MICE; INJURY; DAMAGE; OVEREXPRESSION; PREVENTION AB Preconditioning brain with tumor necrosis factor alpha (TNF-alpha) can induce tolerance to experimental hypoxia and stroke and ceramide is a downstream messenger in the TNF-alpha signaling pathway. A hypoxic-ischemic (HI) insult in the immature rat injures brain primarily through apoptosis. Apoptosis is regulated by Bcl-2 family proteins. The authors explored whether ceramide protects against HI in the immature rat, and whether Bcl-2 family protein expression is involved. Hypoxia-ischemia was produced in seven-day-old rats by ligating the right carotid artery, followed by 2 hours of 8% oxygen exposure. Thirty minutes after HI, C-2-ceramide (150 mug/kg) was injected intraventricularly. Infarct volume was measured 5 days later. C-2-ceramide reduced HI-induced brain damage by 45% to 65% compared with HI/dimethyl sulfoxide (DMSO) (vehicle control) or HI only groups. In separate experiments, brains of sham-operated control and HI only animals and animals subjected to HI plus C-2-ceramide or DMSO infusion were sampled 6 hours, 24 hours, and 5 days after treatments and analyzed for Bcl-2, Bcl-xl, and Bax expression (Western blotting), and apoptosis (TUNEL assay). Augmented Bcl-2 and Bcl-xl levels in the C-2-ceramide treated group were associated with a significant decrease in TUNEL-positive cells. The results support a protective role for ceramide in neonatal. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Hallenbeck, JM (reprint author), NINDS, Stroke Branch, NIH, 36 Convent Dr,MSC 4128,Bldg 36,Room 4A03, Bethesda, MD 20892 USA. NR 35 TC 62 Z9 65 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2001 VL 21 IS 1 BP 34 EP 40 PG 7 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 385RC UT WOS:000166016600005 PM 11149666 ER PT J AU Michal, CA Tycko, R AF Michal, CA Tycko, R TI Time-reversal of the evolution of a dipole-coupled, many-spin system under continuous resonant irradiation SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; MULTIPLE-QUANTUM NMR; EXCITATION; FIELD; POLARIZATION; COUPLINGS; SOLIDS AB Time-reversal of the evolution of a dipole-coupled, many-spin system under continuous resonant excitation with a radio-frequency (rf) field of arbitrary amplitude is demonstrated in solid-state H-1 nuclear magnetic resonance (NMR) experiments on polycrystalline adamantane. Time-reversed evolution is accomplished with an rf pulse sequence that generates an effective nuclear spin Hamiltonian that includes both dipole-dipole coupling and rf interaction terms, with signs opposite to those in forward evolution. The amplitude of the effective continuous rf field is varied by varying the phases of rf pulses in the sequence. Experiments show echo-like NMR signals under time-reversed evolution after forward evolution to an apparent quasieguilibrium state under continuous rf excitation. Such echolike signals are inconsistent with the hypothesis of spin temperature in the rotating frame, according to which the approach to quasiequilibrium under continuous rf excitation is an irreversible process. The use of this time-reversed evolution in multiple quantum (MQ) NMR spectroscopy is also demonstrated. MQ NMR spectra obtained with increasing excitation times exhibit a partial confinement of nuclear spin order to zero- and one-quantum operators. This novel behavior is shown to be a consequence of energy conservation. C1 NIH, Chem Phys Lab, NIDDKD, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIH, Chem Phys Lab, NIDDKD, Bldg 5,Room 112, Bethesda, MD 20892 USA. RI Michal, Carl/G-5288-2012 OI Michal, Carl/0000-0002-5764-3221 NR 24 TC 5 Z9 5 U1 2 U2 6 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD JAN 1 PY 2001 VL 114 IS 1 BP 409 EP 415 DI 10.1063/1.1330239 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 388LU UT WOS:000166182900047 ER PT J AU Ito, Y Shinomiya, K AF Ito, Y Shinomiya, K TI A new continuous-flow cell separation method based on cell density: Principle, apparatus, and preliminary application to separation of human buffy coat SO JOURNAL OF CLINICAL APHERESIS LA English DT Article DE seal-less continuous flow centrifuge; Percoll density gradient separation; human buffy coat; granulocytes; lymphocytes; CD 34 cells AB With the recent progress in transfusion medicine, separation and isolation of cells in a large quantity is becoming increasingly important. At present, the continuous cell separation method in a preparative scale is limited to apheresis and elutriation: the former is mainly used for collection of platelet and buffy coat from the whole blood. while the latter separates cells virtually according to their size. Here we introduce a continuous flow method that separates cells entirely based on cell density. The method is gentle and capable of processing a large number of cells. The potential capability of the method was demonstrated on separation of lymphocytes and granulocytes from human buffy coat. Lymphocytes were enriched to 90% in the fraction at density = 1.065 and granulocytes are isolated in fractions at density = 1.075-1.080 while red cells were completely retained at the periphery of the channel. CD34 cells were distributed around 1.065 and coeluted with lymphocytes, suggesting that further enrichment requires focusing the density gradient around 1.070. The method could process 10 9 nucleated cells in 2 hours. Our preliminary results suggest that the present method is an effective and efficient means to separate blood cells. J. Clin. Apheresis 16:186-191, 2001. Published 2001 Wiley-Liss, Inc.dagger C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Room 3334, Bethesda, MD 20892 USA. NR 5 TC 13 Z9 13 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0733-2459 J9 J CLIN APHERESIS JI J. Clin. Apheresis PY 2001 VL 16 IS 4 BP 186 EP 191 DI 10.1002/jca.1032 PG 6 WC Hematology SC Hematology GA 508ZU UT WOS:000173120300005 PM 11835415 ER PT J AU Merke, DP Cho, D Calis, KA Keil, MF Chrousos, GP AF Merke, DP Cho, D Calis, KA Keil, MF Chrousos, GP TI Hydrocortisone suspension and hydrocortisone tablets are not bioequivalent in the treatment of children with congenital adrenal hyperplasia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTISOL AB In July 1998, Cortef oral suspension (Pharmacia & Upjohn) was reformulated changing the suspending agent tragacanth to xanthan gum. We subsequently observed suboptimal control of hormone levels in a group of children with classic congenital adrenal hyperplasia, despite increasing doses of Cortef suspension and stringent instructions to parents regarding shaking of the bottles of medication. Nineteen children receiving Cortef and fludrocortisone therapy were changed to hydrocortisone tablets and fludrocortisone, with a 10 percent reduction in hydrocortisone dose. A significant decrease in 17-hydroxyprogesterone (235 +/- 120 vs. 27 +/- 7 nmol/L; p less than or equal to0.001) and androstenedione (18.9 +/- 18.0 vs. 3.5 +/- 3.5 nmol/L; p=0.002) was observed 4-6 weeks later. Twenty-one percent (4/19) had 17-hydroxyprogesterone and androstenedione levels at or below the detection limit of the assay. Despite a significant reduction in glucocorticoid dose (19.6 +/- 4.7 vs. 17.6 +/- 3.9 mg/M(2)/day; p<0.001), eight children experienced significant weight gain and appetite increase, three experienced trouble sleeping, four experienced moodiness, and three developed hypertension requiring a decrease in fludrocortisone therapy. Hydrocortisone dose was further decreased to 15.2 +/- 2.6 mg/M(2)/day with resolution of symptoms. We conclude that Cortef suspension and hydrocortisone tablets are not bioequivalent and the reformulated form of hydrocortisone oral suspension was inadequate in the control of children with congenital adrenal hyperplasia. Cortef suspension has been recalled as a result of these data. C1 NICHHD, Warren Grant Magnuson Clin Ctr, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. US PHS, Washington, DC 20201 USA. RP Merke, DP (reprint author), NICHHD, Warren Grant Magnuson Clin Ctr, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 7 TC 17 Z9 19 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2001 VL 86 IS 1 BP 441 EP 445 DI 10.1210/jc.86.1.441 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 395KT UT WOS:000166580100071 PM 11232038 ER PT J AU LaValley, MP McAlindon, TE Chaisson, CE Levy, D Felson, DT AF LaValley, MP McAlindon, TE Chaisson, CE Levy, D Felson, DT TI The validity of different definitions of radiographic worsening for longitudinal studies of knee osteoarthritis SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE construct validity; discriminant power; framingham study; longitudinal data; progression; responsiveness ID OSTEO-ARTHRITIS; PROGRESSION; JOINT; ASSOCIATION AB Several definitions have been used to characterize radiographic worsening of knee osteoarthritis in longitudinal studies, yet a valid definition with maximal power to detect differences between groups is not known. We used serial radiographs from the Framingham Osteoarthritis Study to compare five dichotomous definitions according to construct validity (strength of association) and discriminant power (power to reject null hypotheses of no difference) for 1) known risk factors for knee osteoarthritis, and 2) development of new knee pain. For risk factors: definitions that included scores for osteophytes (bone spurs) showed good construct validity and discriminant power, a definition using the Kellgren and Lawrence grade of overall knee osteoarthritis was conservative with good construct validity but low discriminant power: a definition based solely on ordinal assessment of joint space narrowing had weak construct validity and low discriminant power. AII definitions had comparably strong associations with the development of new knee pain. similar associations with new knee pain were found when the analysis was confined to either knees with no osteoarthritis at baseline or knees with prevalent osteoarthritis, with increased standard errors for prevalent osteoarthritis. Use of any of these definitions, other than joint space narrowing alone, would permit detection of associations with most known risk factors. Definitions incorporating both osteophytes and joint space narrowing offer the most precise estimation of the association of risk factors with disease worsening. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Boston Univ, Arthrit Ctr, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP LaValley, MP (reprint author), Boston Univ, Arthrit Ctr, A203,715 Albany St, Boston, MA 02118 USA. FU NHLBI NIH HHS [N01-HC-38038]; NIA NIH HHS [AG 09300]; NIAMS NIH HHS [AR 20613] NR 26 TC 27 Z9 27 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JAN PY 2001 VL 54 IS 1 BP 30 EP 39 DI 10.1016/S0895-4356(00)00273-0 PG 10 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 394XY UT WOS:000166550700003 PM 11165466 ER PT J AU Coady, SA Sorlie, PD Cooper, LS Folsom, AR Rosamond, WD Conwill, DE AF Coady, SA Sorlie, PD Cooper, LS Folsom, AR Rosamond, WD Conwill, DE TI Validation of death certificate diagnosis for coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE validity; coronary heart disease; death certificate; community surveillance; sudden death; mortality ID SUDDEN-DEATH; MYOCARDIAL-INFARCTION; VITAL STATISTICS; MORTALITY; ACCURACY; CRITERIA; PROGRAM; AUTOPSY; TRENDS AB The validity of the death certificate in identifying coronary heart disease deaths was evaluated using data from the community surveillance component of the Atherosclerosis Risk in Communities Study (ARIC). Deaths in the four ARIC communities of Forsyth Co., NC; Jackson, MS; Minneapolis, MN; and Washington Co., MD were selected based on underlying cause of death codes as determined by the rules of the ninth revision of the International Classification of Diseases (ICD-9). Information about the deaths was gathered through informant interviews, physician or coroner questionnaires, and medical record abstraction, and was used to validate the cause of death. Sensitivity, specificity, and positive predictive value of the death certificate classification of CHD death (ICD-9 codes 410-414 and 429.2) were estimated by comparison with the validated cause of death based on physician review of all available information. Results from 9 years of surveillance included a positive predictive value 0.67 (95% CI 0.66-0.68), sensitivity of 0.81 (95% CI 0.79-0.83), and a false-positive rate ii-specificity) of 0.28 (95% CI 0.26-0.30). Comparing CHD deaths as defined by the death certificate with validated CHD deaths indicated that the death certificate overestimated CHD mortality by approximately 20% in the ARIC communities. Within subgroups, death certificate overestimation was reduced with advancing age (up to age 74), was consistent over time, was not dependent on gender, and exhibited considerable variation among communities. (C) 2001 Elsevier Science Inc. All rights reserved. C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20982 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Univ N Carolina, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. Univ Mississippi, Med Ctr, Div Epidemiol, Jackson, MS 39216 USA. RP Coady, SA (reprint author), NHLBI, Div Epidemiol & Clin Applicat, 2 Rockledge Ctr,6701 Rockledge Dr,MSC 7934, Bethesda, MD 20982 USA. NR 28 TC 79 Z9 81 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JAN PY 2001 VL 54 IS 1 BP 40 EP 50 DI 10.1016/S0895-4356(00)00272-9 PG 11 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 394XY UT WOS:000166550700004 PM 11165467 ER PT J AU Gilbert, P Self, S Rao, M Naficy, A Clemens, J AF Gilbert, P Self, S Rao, M Naficy, A Clemens, J TI Sieve analysis: methods for assessing from vaccine trial data how vaccine efficacy varies with genotypic and phenotypic pathogen variation SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE clinical trials; genetic sequence variation; human immunodeficiency virus; molecular epidemiology; sieve analysis; statistical methods ID IMMUNODEFICIENCY-VIRUS TYPE-1; PNEUMOCOCCAL POLYSACCHARIDE VACCINES; HUMAN MONOCLONAL-ANTIBODY; ORAL CHOLERA VACCINES; SICKLE-CELL DISEASE; STREPTOCOCCUS-PNEUMONIAE; PROTECTIVE EFFICACY; ROTAVIRUS VACCINE; LOGRANK TEST; FIELD TRIAL AB A key component in the evaluation of efficacy of a vaccine to protect against disease caused by an antigenically diverse infectious pathogen in a preventative vaccine trial is assessing how vaccine-induced protection depends on genotypic and phenotypic variations of the exposing pathogen. This assessment is made by comparing pathogen isolates between infected vaccinated subjects and infected unvaccinated subjects. A survey of efficacy trial reports reveals a lack of systematic, quantitative investigation in this question. Analysis tools for testing if vaccine protection against disease is superior against some pathogen strains, and for estimating the magnitude of this differential vaccine protection, are described. The broad applicability of the methods is illustrated through analysis of isolates taken from persons infected while participating in vaccine trails for cholera, HIV-1, hepatitis B, rotavirus, and pneumococcus. These analyses reveal intriguing trends for Genentech's monovalent rgp120 HIV-1 vaccine, for two whole-killed-cell oral cholera vaccines, and for other vaccines. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NICHHD, Bethesda, MD 20892 USA. RP Gilbert, P (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. NR 65 TC 20 Z9 21 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JAN PY 2001 VL 54 IS 1 BP 68 EP 85 DI 10.1016/S0895-4356(00)00258-4 PG 18 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 394XY UT WOS:000166550700007 PM 11165470 ER PT J AU Hostetter, TH AF Hostetter, TH TI Hypertrophy and hyperfunction of the diabetic kidney SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID TUBULAR REABSORPTION; RENAL HYPERTROPHY; MELLITUS C1 Univ Minnesota, Minneapolis, MN USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Hostetter, TH (reprint author), NIDDK, 6707 Democracy Blvd,Room 625, Bethesda, MD 20892 USA. NR 11 TC 25 Z9 25 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2001 VL 107 IS 2 BP 161 EP 162 DI 10.1172/JCI12066 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 393FE UT WOS:000166457900006 PM 11160131 ER PT J AU Warshawsky, I Hortin, GL AF Warshawsky, I Hortin, GL TI Effect of substrate size an immunoinhibition of amylase activity SO JOURNAL OF CLINICAL LABORATORY ANALYSIS LA English DT Article DE amylase; immunoassay; enzyme immunoassay; amylase isoenzymes; chromogenic substrates; macromolecular substrates ID HOMOGENEOUS ENZYME-IMMUNOASSAY; HUMAN ALPHA-AMYLASE; EXCLUSION CHROMATOGRAPHY; BETA-GALACTOSIDASE; HUMAN SALIVARY; ISOENZYMES; ANTIBODIES; ASSAY; SERUM AB Immunoinhibition assays are hypothesized to work by antibodies blocking substrate access to enzyme active sites. To test this hypothesis, the inhibition of amylase isoenzymes by monoclonal and polyclonal antisera was assessed using substrates of varying sizes: chromogenic sustrates 3, 5, or 7 glucose units in length, novel synthetic macromolecular substrates, and starch. The synthetic macromolecular substrates consisted of small oligosaccharide substrates linked to an inert polymer that conferred a large size to substrate molecules as determined by gel filtration chromatography. When substrate size increased, amylase activity could be inhibited equivalently by antibody concentrations that are 10-fold lower. Progressively less polyclonal serum was required to inhibit amylase activity as substrate length increased from 3 to 5 to 7 glucose units and as size was increased by linkage to a polymer. Different effects of substrate size were observed with two monoclonal antibodies. One monoclonal antibody blocked amylase activity independent of substrate size, while another monoclonal antibody had little inhibitory effect except using starch as substrate. We conclude that use of larger substrates can expand the repertoire of inhibitory epitopes on enzymes and convert a noninhibitory antibody into an inhibitory one. C1 NIH, Dept Clin Pathol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Dept Clin Pathol, Warren Grant Magnuson Clin Ctr, NIH Bldg 10,Room 2C-407,10 Ctr Dr, Bethesda, MD 20892 USA. EM ghortin@cc.nih.gov NR 23 TC 3 Z9 3 U1 3 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-8013 J9 J CLIN LAB ANAL JI J. Clin. Lab. Anal. PY 2001 VL 15 IS 2 BP 64 EP 70 DI 10.1002/jcla.3 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 419GQ UT WOS:000167941300003 PM 11291107 ER PT J AU Hisada, M Lee, MG Hanchard, B Owens, M Song, QS van Doorn, LJ Cutler, AF Gold, BD AF Hisada, M Lee, MG Hanchard, B Owens, M Song, QS van Doorn, LJ Cutler, AF Gold, BD TI Characteristics of Helicobacter pylori infection in Jamaican adults with gastrointestinal symptoms SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CAGA; VACA; GASTRITIS; RESPONSES; STRAINS; ICEA; PCR AB Helicobacter pylori infection is common in Jamaica. Describing its epidemiology in a population-based study depends largely on serology, but serologic assays have not been validated in this population, To address this issue, we examined the presence of H. pylori infection in 30 sequential adult patients with gastroduodenal symptoms by three biopsy-based methods (rapid urease test, histology, and culture) as well as by one research and two commercial enzyme-linked immunosorbent assays (ELISAs), A patient was considered H. pylori positive if the organism was detected by at least one biopsy-based method. Eighteen (60%) of the 30 patients were H. pylori positive by these criteria, whereas 21 (70%) were seropositive for H. pylori immunoglobulin G by our research ELISA. The presence of H. pylori infection in patients with gastric cancer and those with chronic gastritis was missed by biopsy-based methods but was detected by serologic assays, This observation indicates that serologic assays may be better suited for the detection of this infection in a population in which H. pylori-associated pathology is prevalent. The performance of our research ELISA in detecting biopsy-based H. pylori-positive cases was excellent, with a sensitivity and specificity of 100% and 75%, respectively. Molecular genotyping of the isolates revealed that the predominant H. pylori genotypes in this cohort of Jamaicans were cagA(+) vacA slb-m1, and iceA2, The validated serologic assay enables us to interpret epidemiologic data from population-based studies in Jamaica by comparison to those from other populations. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ W Indies, Dept Med, Kingston 7, Jamaica. Univ W Indies, Dept Pathol, Kingston 7, Jamaica. Emory Univ, Sch Med, Dept Pediat, Div Pediat Gastroenterol & Nutr, Atlanta, GA USA. Delft Diagnost Lab, Delft, Netherlands. Mt Sinai Hosp, Detroit, MI USA. RP Hisada, M (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8008, Rockville, MD 20852 USA. NR 26 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2001 VL 39 IS 1 BP 212 EP 216 DI 10.1128/JCM.39.1.212-216.2001 PG 5 WC Microbiology SC Microbiology GA 393KZ UT WOS:000166468900035 PM 11136773 ER PT J AU Soini, H Pan, X Teeter, L Musser, JM Graviss, EA AF Soini, H Pan, X Teeter, L Musser, JM Graviss, EA TI Transmission dynamics and molecular characterization of Mycobacterium tuberculosis isolates with low copy numbers of IS6110 SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID FRAGMENT-LENGTH-POLYMORPHISM; ELEMENT PCR METHOD; STRAIN DIFFERENTIATION; PULMONARY TUBERCULOSIS; COMPLEX STRAINS; EPIDEMIOLOGY; IDENTIFICATION; MARKERS AB Population-based analysis of Mycobacterium tuberculosis transmission in Houston, Tex,, over 5 years identified 377 patients infected with an isolate containing one to four copies of IS6110, The isolates were analyzed by spoligotyping and assigned to one of three major genetic groups based on nucleotide polymorphisms in codons katG 463 and gyrA 95, Prospectively obtained patient interviews were reviewed to assess epidemiologic links between apparently clustered patients. A total of 13 groups of isolates with the same IS6110 profile were identified, representing 326 of the 377 patients (86.5%; range 2 to 113 patients). In contrast, 28 groups of isolates containing 334 patients (88.6%) had the same spoligotype (range, 2 to 143 patients). Combination of IS6110 profile and spoligotype data identified 31 clusters with 300 patients (79.6%; range, 2 to 82 patients). All 377 Isolates belonged to major genetic group 1 (77 patients) or genetic group 2 (300 patients); no major genetic group 3 isolates were identified. Among the 228 patients interviewed, 33 patients (14.5%) were directly linked to another patient in the same cluster. Possible epidemiologic links were also found among 11 patients. Moreover, many clusters consisted of individuals with the same ethnicity. In conclusion, we confirmed that IS6110 profiling and spoligotyping together provide enhanced molecular discrimination of M. tuberculosis isolates with low copy numbers of IS6110. Identification of epidemiologic links among some of the patients verified that the combination of these two methods reliably indexes tuberculosis transmission. C1 Baylor Coll Med, Dept Pathol 209E, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Graviss, EA (reprint author), Baylor Coll Med, Dept Pathol 209E, 1 Baylor Plaza, Houston, TX 77030 USA. FU NIDA NIH HHS [DA09238] NR 23 TC 36 Z9 38 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2001 VL 39 IS 1 BP 217 EP 221 DI 10.1128/JCM.39.1.217-221.2001 PG 5 WC Microbiology SC Microbiology GA 393KZ UT WOS:000166468900036 PM 11136774 ER PT J AU Anderson, WF Chu, KC Chatterjee, N Brawley, O Brinton, LA AF Anderson, WF Chu, KC Chatterjee, N Brawley, O Brinton, LA TI Tumor variants by hormone receptor expression in white patients with node-negative breast cancer from the surveillance, epidemiology, and end results database SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LATE-STAGE DIAGNOSIS; ESTROGEN-RECEPTOR; PROGESTERONE-RECEPTOR; STEROID-RECEPTORS; RISK-FACTORS; SOCIOECONOMIC-STATUS; FAMILY HISTORY; RACE; SURVIVAL; WOMEN AB Purpose: Hormone receptor expression (presence-positive or absence-negative) may reflect different stages of one disease or different breast cancer types. Determining whether hormone receptor expression represents one or more breast cancer phenotypes would have important paradigmatic and practical implications. Methods: Breast cancer records were obtained from the National Cancer institute's Surveillance, Epidemiology, and End Results (SEER) database. The study included 19,541 non-Hispanic white women with node-negative breast cancer. Standard tumor cell characteristics and breast cancer-specific survival were analyzed by independent estrogen receptor (ER+ and ER-), independent progesterone receptor (PR+ and PR-), and joint ERPR expression (ER+PR+, ER+PR-, ER-PR+, and ER-PR-), Results: Age frequency density plots by hormone receptor expression showed two overlapping breast cancer populations with early-onset and/or late-onset etiologies. Independent ER+ and PR+ phenotype were associated with smaller tumor sizes, better grade, and better cancer-specific survival than ER- and PR- breast cancer types. Joint ERPR phenotype exhibited biologic gradients for tumor rite, grader and cancer-specific survival, which ranked from good to worse for ER+PR+ to ER+PR- to ER-PR+ to ER-PR-, Conclusion: Variations of standard tumor cell characteristics and breast cancer-specific survival by hormone receptor expression in white patients with node-negative breast cancer suggested two breast cancer phenotypes with overlapping etiologies and distinct clinical featured. J Clin Oncol 19:18-27. (C) 2001 by American Society of Clinical Oncology. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Off Special Populat Res, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Anderson, WF (reprint author), NCI, Div Canc Prevent, Room EPN 211L,MSC-7322,6130 Execut Blvd, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 71 TC 95 Z9 97 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2001 VL 19 IS 1 BP 18 EP 27 PG 10 WC Oncology SC Oncology GA 389FT UT WOS:000166228500003 PM 11134191 ER PT J AU Goldman, DP Schoenbaum, ML Potosky, AL Weeks, JC Berry, SH Escarce, JJ Weidmer, BA Kilgore, ML Wagle, N Adams, JL Figlin, RA Lewis, JH Cohen, J Kaplan, R McCabe, M AF Goldman, DP Schoenbaum, ML Potosky, AL Weeks, JC Berry, SH Escarce, JJ Weidmer, BA Kilgore, ML Wagle, N Adams, JL Figlin, RA Lewis, JH Cohen, J Kaplan, R McCabe, M TI Measuring the incremental cost of clinical cancer research SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BREAST-CANCER; TRIALS; CARE; BARRIERS; CHEMOTHERAPY; KNOWLEDGE; ATTITUDES AB Purpose: To summarise evidence on the costs of treating patients in clinical trials and to describe the Cost of Cancer Treatment Study, an ongoing effort to produce generalizable estimates of the incremental costs of government-sponsored cancer trials. Methods: A retrospective study of costs will be conducted with 1,500 cancer patients recruited from ct randomly selected sample of institutions in the United States. Patients accrued to either phase II or phase III National Cancer Institute-sponsored clinical trials during a 15-month period will be asked to participate in a study of their health care utilization (n = 750). Costs will be measured approximately 1 year after their trial enrollment from a combination of billing records, medical records, and an in-person survey questionnaire. Similar data will be collected for a comparable group of cancer patients not in trials (n = 750) to provide an estimate of the incremental colt. Results: Evidence suggests insurers limit access to trials because of cost concerns. Public and private efforts are underway to change these policies, but their permanent status is unclear. previous studies found that treatment costs in clinical trials are similar to costs of standard therapy. However, it is difficult to generalize from these studies because of the unique practice settings, insufficient sample sizes, and the exclusion of potentially important costs. Conclusion: Denials of coverage for treatment in a clinical trial limit patient access to trials and could impede clinical research. Preliminary estimates suggest changes to these policies would not be expensive, but these results are not generalizable. The Cost of Cancer Treatment Study is an ongoing effort to provide generalizable estimates of the incremental treatment cost of phase II and phase III cancer trials. The results should be of great interest to insurers and the research community as they consider permanent ways to finance cancer trials. J Clin Oncol 19:105-110. (C) 2001 by American Society of Clinical Oncology. C1 RAND Corp, Santa Monica, CA 90407 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD USA. NCI, Div Canc Treatment & Diag, Bethesda, MD USA. NCI, Off Educ & Special Initiat, Bethesda, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Johnson Comprehens Canc Ctr, Los Angeles, CA USA. Agcy Healthcare Res & Qual, Ctr Cost & Financing Studies, Rockville, MD USA. RP Goldman, DP (reprint author), RAND Corp, 1700 Main St, Santa Monica, CA 90407 USA. NR 30 TC 18 Z9 18 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2001 VL 19 IS 1 BP 105 EP 110 PG 6 WC Oncology SC Oncology GA 389FT UT WOS:000166228500014 PM 11134202 ER PT J AU Hilden, JM Emanuel, EJ Fairclough, DL Link, MP Foley, KM Clarridge, BC Schnipper, LE Mayer, RJ AF Hilden, JM Emanuel, EJ Fairclough, DL Link, MP Foley, KM Clarridge, BC Schnipper, LE Mayer, RJ TI Attitudes and practices among pediatric oncologists regarding end-of-life care: Results of the 1998 American Society of Clinical Oncology survey SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DYING CHILD; PALLIATIVE CARE; CANCER; EUTHANASIA; DEATH; PAIN AB Purpose: In 1998, the American Society of Clinical Oncology (ASCO) surveyed its membership to assess the attitudes, practices, and challenges associated with end-of-life care of patients with cancer. In this report, we summarize the responses of pediatric oncologists and the implications far care of children dying from cancer. Methods: The survey consisted of 118 questions, covering eight categories. All ASCO members in the United States, Canada, and the United Kingdom were mailed a survey, which wets completed by 228 pediatric oncologists, Predictors of particular attitudes and practices were identified using stepwise logistic regression analysis. Potential predictors were age, sex, religious affiliation, importance of religious beliefs, recent death of a relative, specialty, type of practice (rural or urban, academic or nonacademic), amount of time spent in patient care, number of new patients in the past 6 months, and number of patients who died in the past year. Results: Pediatric oncologists reported a lack of formal courses in pediatric palliative care, a strikingly high reliance on trial and error in learning to care for dying children, and a need for strong role models in this area. The lack of an accessible palliative care team or pain service was often identified as ct barrier to good care. Communication difficulties exist between parents and oncologists, especially regarding the shift to end-of-life care and adequate pain control. Conclusion: Pediatric oncologists are working to integrate symptom control, psychosocial support, and palliative care into the routine care of the seriously ill child, although barriers exist that make such comprehensive care a challenge. J Clin Oncol 19:205-212. (C) 2001 by American Society of Clinical Oncology. C1 Childrens Hosp & Clin St Paul, Dept Pediat Hematol Oncol, St Paul, MN 55102 USA. NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. AMC Canc Res Ctr, Ctr Res Methodol & Biometr, Denver, CO USA. Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA. Mem Sloan Kettering Canc Ctr, Pain & Palliat Care Serv, New York, NY 10021 USA. Univ Massachusetts, Beth Israel Deaconess Med Ctr, Survey Res Ctr, Div Hematol & Oncol, Boston, MA 02125 USA. Dana Farber Canc Inst, Dept Med Adult Oncol, Boston, MA 02115 USA. RP Hilden, JM (reprint author), Childrens Hosp & Clin St Paul, Dept Pediat Hematol Oncol, 345 N Smith Ave, St Paul, MN 55102 USA. NR 33 TC 161 Z9 165 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2001 VL 19 IS 1 BP 205 EP 212 PG 8 WC Oncology SC Oncology GA 389FT UT WOS:000166228500026 PM 11134214 ER PT J AU Korn, EL Arbuck, SG Pluda, JM Simon, R Kaplan, RS Christian, MC AF Korn, EL Arbuck, SG Pluda, JM Simon, R Kaplan, RS Christian, MC TI Clinical trial designs for cytostatic agents: Are new approaches needed? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MATRIX METALLOPROTEINASE INHIBITOR; PHASE-I TRIAL; ANTICANCER AGENTS; CANCER; ANGIOGENESIS; THERAPY; IMPROVEMENTS; GEMCITABINE; MARIMASTAT; SELECTION AB Preclinical data suggest that some new anticancer agents directed at novel targets demonstrate tumor growth inhibition but not tumor shrinkage. Such cytostatic agents may offer clinical benefits for patients in the absence of tumor shrinkage. In addition, lower doses of some of these agents may be just as effective as higher doses, implying that toxicity may not be an ideal end point for dose finding. Because of these factors, the sequence and design of traditional phase I, II, and III trials used for cytotoxic agents (which typically shrink tumors and in a dose-dependent manner) may not be appropriate for cytostatic agents. This article discusses options for modifying trial designs to accommodate cytostatic agents. Examples are given where there options have been tried or are currently being tried. Recommendations given for choosing among the trial designs depend on what is known preclinically about the agents (eg, does one have a validated and reproducible biologic end point that can be used to guide a dose escalation?), what is known about the patient population being studied (eg, does one have a well-documented historical progression-free survival rate at 1 year for comparison with the experience of the new agent?), and the numbers of agents and patients available for participation in trials. Planned and ongoing trials will test the utility of some of these new approaches. J Clin Oncol 19:265-272. This is a United States government work. There are no restrictions on its use. C1 NCI, Biometr Res Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, EPN-739, Bethesda, MD 20892 USA. NR 33 TC 219 Z9 228 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2001 VL 19 IS 1 BP 265 EP 272 PG 8 WC Oncology SC Oncology GA 389FT UT WOS:000166228500034 PM 11134222 ER PT J AU Pearson, JL Stanley, B King, CA Fisher, CB AF Pearson, JL Stanley, B King, CA Fisher, CB TI Intervention research with persons at high risk for suicidality: Safety and ethical considerations SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Suicide Prevention Intervention CY OCT 24, 2000 CL BOSTON, MA ID ADOLESCENT SUICIDE; MANAGEMENT; SETTINGS; BEHAVIOR; OUTCOMES; ABUSE AB There is a critical need for studies designed to reduce suicidality. Individuals at high risk for suicidality deserve safe and effective treatments, just as do other individuals with mental disorders who do not experience suicidality. Points for consideration regarding safety and monitoring procedures are offered to help researchers who conduct treatment trials with individuals who have mental disorders and investigators specifically interested in developing treatments to reduce suicidality. Issues such as study design, increased monitoring and supervision, research clinician competencies, and liability concerns are addressed. Points to consider in planning an intervention trial, a checklist of informed consent issues, and a list of relevant active federal regulations are provided. C1 NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Columbia Univ, New York, NY USA. Univ Michigan, Ann Arbor, MI 48109 USA. Fordham Univ, Bronx, NY 10458 USA. RP Pearson, JL (reprint author), NIMH, Div Serv & Intervent Res, 6001 Execut Blvd,Room 7160 MSC 9635, Bethesda, MD 20892 USA. RI Stanley, Barbara/J-8736-2013 FU NIMHD NIH HHS [263-MD 004930, 263-MD004929, 263-MD004928] NR 43 TC 39 Z9 39 U1 1 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2001 VL 62 SU 25 BP 17 EP 26 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 501MH UT WOS:000172688100003 PM 11765091 ER PT J AU Thierry, KL Spence, MJ Memon, A AF Thierry, Karen L. Spence, Melanie J. Memon, Amina TI Before Misinformation is Encountered: Source Monitoring Decreases Child Witness Suggestibility SO JOURNAL OF COGNITION AND DEVELOPMENT LA English DT Article AB This research examines whether young children are less suggestible if they monitor the source of acquired information. Events from 2 sources-live and videotaped science demonstrations-were observed by 3- to 4-year-olds (n = 39) and 5- to 6-year-olds (n = 36) in Experiment 1. One half of the children in each age group were administered a source-monitoring (SM) test that required reporting the source of science events. Control group children received recognition questions without source cues. Afterward, all children freely recalled the events and were then asked misleading questions about the source of events. Control 3- to 4-year-olds were less accurate than all other groups in free recall and in response to misleading-detail questions, whereas SM 3- to 4-year-olds' performance was equivalent to that of both groups of 5- to 6-year-olds. Experiment 2 examined one possible reason for the apparent lack of effect of the SM manipulation among the 5- to 6-year-olds: namely, that free recall served as an SM opportunity for them. To test this hypothesis, 5- to 6-year-olds' (n = 38) responses to misleading questions were examined when the free-recall task was omitted from the procedure. The SM group was more accurate than the control group, suggesting that free recall served as an SM task for 5- to 6-year-olds in Experiment 1. These results implicate SM as one factor underlying young children's suggestibility. C1 [Thierry, Karen L.; Spence, Melanie J.] Univ Texas Dallas, Sch Human Dev, Richardson, TX 75083 USA. [Memon, Amina] Univ Aberdeen, Dept Psychol, Old Aberdeen, Scotland. RP Thierry, KL (reprint author), NICHHD, Sect Social & Emot Dev, BSA Bldg,Room 331,9190 Rockville Pike, Bethesda, MD 20892 USA. EM thierryk@mail.nih.gov NR 47 TC 27 Z9 28 U1 0 U2 4 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1524-8372 J9 J COGN DEV JI J. Cogn. Dev. PY 2001 VL 2 IS 1 BP 1 EP 26 DI 10.1207/S15327647JCD0201_1 PG 26 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA V12QK UT WOS:000207613500001 ER PT J AU Barkmeier, JM Case, JL Ludlow, CL AF Barkmeier, JM Case, JL Ludlow, CL TI Identification of symptoms for spasmodic dysphonia and vocal tremor: a comparison of expert and nonexpert judges SO JOURNAL OF COMMUNICATION DISORDERS LA English DT Article DE spasmodic dysphonia; vocal tremor; evaluation ID LARYNGEAL MUSCLE-ACTIVITY; TENSION DYSPHONIA; SPASTIC DYSPHONIA; VOICE TREMOR AB Spasmodic dysphonia is a rare voice disorder that is most successfully treated by injection of botulinum toxin (i.e., BOTOX) into the affected laryngeal muscles. BOTOX is currently available for use by professionals outside of metropolitan voice centers who may be unfamiliar with this rare disorder. Patients may seek assessment and treatment locally from clinicians who are unfamiliar with the speech symptoms for adductor-type (ADSD) or abductor-type (ABSD) spasmodic dysphonia. Although these disorders have been described in the literature, the symptoms have not been well defined and may appear similar to those of vocal tremor or muscle tension dysphonia (MTD). Thus, patients with spasmodic dysphonia might not be easily identified by local clinicians for treatment. The purpose of the current study was to determine whether voice clinicians with infrequent exposure to patients with spasmodic dysphonia could learn to identify speech symptoms for ADSD and ABSD comparable to voice clinicians with extensive experience with these disorders. The ratings of five nonexpert judges were compared to the ratings obtained from three expert judges. The results of this study demonstrated that nonexpert judges could be trained to identify the speech symptoms associated with ADSD, ABSD, and vocal tremor. While the nonexpert judges tended towards false positive judgements for the speech symptoms of interest, the overall speech symptom profiles for each type of voice disorder appeared comparable to those obtained from the expert judges. The symptom identification scales used, therefore, have potential for use by clinicians unfamiliar with these disorders for correctly identifying persons with symptoms of ADSD and ABSD. Educational objectives: Readers will be able to (1) define the predominant speech symptoms reflective of the voice disorder categories of ABSD, ADSD, and vocal tremor; and (2) describe the methods utilized in a new perceptual training protocol for teaching clinicians how to identify predominant speech symptoms associated with the voice disorder categories of ABSD, ADSD, and vocal tremor. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Univ Arizona, Dept Speech & Hearing Sci, Tucson, AZ 85721 USA. Arizona State Univ, Tempe, AZ 85287 USA. NINDS, Laryngeal & Speech Sect, Bethesda, MD 20892 USA. RP Barkmeier, JM (reprint author), Univ Arizona, Dept Speech & Hearing Sci, POB 210071,1131 E 2nd Ave, Tucson, AZ 85721 USA. OI Ludlow, Christy/0000-0002-2015-6171 NR 19 TC 21 Z9 22 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0021-9924 J9 J COMMUN DISORD JI J. Commun. Disord. PD JAN-APR PY 2001 VL 34 IS 1-2 BP 21 EP 37 DI 10.1016/S0021-9924(00)00039-3 PG 17 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 416PZ UT WOS:000167790500003 PM 11322567 ER PT J AU Leibowitz, N Nussinov, R Wolfson, HJ AF Leibowitz, N Nussinov, R Wolfson, HJ TI MUSTA - A general, efficient, automated method for multiple structure alignment and detection of common motifs: Application to proteins SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE multiple structure alignment; geometric hashing; invariants; structural core; multiple structure comparison ID DATA-BANK; SEQUENCE; SUBSTRUCTURES; SIMILARITIES; ALGORITHMS; FAMILIES; CORE AB Here we present an algorithm designed to carry out multiple structure alignment and to detect recurring substructural motifs. So far we have implemented it for comparison of protein structures. However, this general method is applicable to comparisons of RNA structures and to detection of a pharmacophore in a series of drug molecules. Further, its sequence order independence permits its application to detection of motifs on protein surfaces, interfaces, and binding/active sites. While there are many methods designed to carry out pairwise structure comparisons, there are only a handful geared toward the multiple structure alignment task. Most of these tackle multiple structure comparison as a collection of pairwise structure comparison tasks. The multiple structural alignment algorithm presented here automatically finds the largest common substructure (core) of atoms that appears in all the molecules in the ensemble. The detection of the core and the structural alignment are done simultaneously. The algorithm begins by finding small substructures that are common to all the proteins in the ensemble. One of the molecules is considered the reference; the others are the source molecules. The small substructures are stored in special arrays termed combinatorial buckets, which define sets of multistructural alignments from the source molecules that coincide with the same small set of reference atoms (C-alpha-atoms here). These substructures are initial small fragments that have congruent copies in each of the proteins. The substructures are extended, through the processing of the combinatorial buckets, by clustering the superpositions (transformations), The method is very efficient. C1 Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Fac Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Intramural Res Support Program, Frederick, MD 21702 USA. RP Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. EM ruthn@ncifcrf.gov RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [N01-CO-56000] NR 37 TC 48 Z9 49 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 EI 1557-8666 J9 J COMPUT BIOL JI J. Comput. Biol. PY 2001 VL 8 IS 2 BP 93 EP 121 DI 10.1089/106652701300312896 PG 29 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 451GP UT WOS:000169793200001 PM 11454300 ER PT J AU Wolfinger, RD Gibson, G Wolfinger, ED Bennett, L Hamadeh, H Bushel, P Afshari, C Paules, RS AF Wolfinger, RD Gibson, G Wolfinger, ED Bennett, L Hamadeh, H Bushel, P Afshari, C Paules, RS TI Assessing gene significance from cDNA microarray expression data via mixed models SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE ANOVA; cDNA microarray; gene expression; mixed models; statistical significance ID DISCOVERY AB The determination of a list of differentially expressed genes is a basic objective in many cDNA microarray experiments. We present a statistical approach that allows direct control over the percentage of false positives in such a list and, under certain reasonable assumptions, improves on existing methods with respect to the percentage of false negatives. The method accommodates a wide variety of experimental designs and can simultaneously assess significant differences between multiple types of biological samples. Two interconnected mixed linear models are central to the method and provide a flexible means to properly account for variability both across and within genes. The mixed model also provides a convenient framework for evaluating the statistical power of any particular experimental design and thus enables a researcher to a priori select an appropriate number of replicates. We also suggest some basic graphics for visualizing lists or significant genes. Analyses of published experiments studying human cancer and yeast cells illustrate the results. C1 SAS Inst Inc, Cary, NC 27513 USA. N Carolina State Univ, Dept Genet, Raleigh, NC 27695 USA. Meredith Coll, Dept Biol, Raleigh, NC 27607 USA. NIEHS, Microarray Ctr, Res Triangle Pk, NC 27709 USA. RP Wolfinger, RD (reprint author), SAS Inst Inc, Cary, NC 27513 USA. NR 33 TC 761 Z9 777 U1 3 U2 21 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PY 2001 VL 8 IS 6 BP 625 EP 637 DI 10.1089/106652701753307520 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 503MK UT WOS:000172802100005 PM 11747616 ER PT J AU Villoutreix, BO Covell, DG Blom, AM Wallqvist, A Friedrich, U Dahlback, B AF Villoutreix, BO Covell, DG Blom, AM Wallqvist, A Friedrich, U Dahlback, B TI Screening the molecular surface of human anticoagulant protein C: A search for interaction sites SO JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN LA English DT Article DE coagulation; protein C; protein interaction; protein modelling; thrombin ID BLOOD-COAGULATION FACTOR; THROMBIN-THROMBOMODULIN COMPLEX; SOLUBLE TISSUE FACTOR; CRYSTAL-STRUCTURE; ACTIVE-SITE; FACTOR-VIIA; MEMBRANE-SURFACE; GLA DOMAIN; FACTOR-V; X-RAY AB Protein C (PC), a 62 kDa multi-modular zymogen, is activated to an anticoagulant serine protease (activated PC or APC) by thrombin bound to thrombomodulin on the surface of endothelial cells. PC/APC interacts with many proteins and the characterisation of these interactions is not trivial. However, molecular modelling methods help to study these complex biological processes and provide basis for rational experimental design and interpretation of the results. PC/APC consists of a Gla domain followed by two EGF modules and a serine protease domain. In this report, we present two structural models for full-length APC and two equivalent models for full-length PC, based on the X-ray structures of Gla-domainless APC and of known serine protease zymogens. The overall elongated shape of the models is further cross-validated using size exclusion chromatography which allows evaluation of the Stokes radius (r(s) for PC = 33.15 Angstrom; r(s) for APC = 34.19 Angstrom), frictional ratio and axial ratio. We then propose potential binding sites at the surface of PC/APC using surface hydrophobicity as a determinant of the preferred sites of intermolecular recognition. Most of the predicted binding sites are consistent with previously reported experimental data, while some clusters highlight new regions that should be involved in protein-protein interactions. C1 INSERM, U428, Sch Pharm, F-75006 Paris, France. NCI, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. Lund Univ, Malmo Univ Hosp, Dept Clin Chem, Wallenberg Lab, S-20502 Malmo, Sweden. Rutgers State Univ, Dept Chem, Piscataway, NJ 08855 USA. RP Villoutreix, BO (reprint author), INSERM, U428, Sch Pharm, 4 Ave Observ, F-75006 Paris, France. EM villoutreix@pharmacie.univ-paris5.fr RI Blom, Anna/B-9607-2009 OI Blom, Anna/0000-0002-1348-1734 NR 65 TC 12 Z9 12 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-654X J9 J COMPUT AID MOL DES JI J. Comput.-Aided Mol. Des. PD JAN PY 2001 VL 15 IS 1 BP 13 EP 27 DI 10.1023/A:1011158717139 PG 15 WC Biochemistry & Molecular Biology; Biophysics; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Biophysics; Computer Science GA 390CT UT WOS:000166278400002 PM 11219426 ER PT J AU Florell, SR Egan, CA Gregory, MC Zone, JJ Petersen, MJ AF Florell, SR Egan, CA Gregory, MC Zone, JJ Petersen, MJ TI Eosinophilic fasciitis occurring four weeks after the onset of dialysis in a renal failure patient SO JOURNAL OF CUTANEOUS MEDICINE AND SURGERY LA English DT Editorial Material ID L-TRYPTOPHAN; HEMODIALYSIS-PATIENTS; MYALGIA-SYNDROME; DISEASE; ASSOCIATION; INVOLVEMENT; FEATURES AB Background: Eosinophilic fasciitis is a rare, scleroderma-like disease that usually affects the extremities of young to middle-aged males. The disease may cause flexion contractures and limit joint mobility and is associated with peripheral eosinophilia. The fascia, by definition, is infiltrated with mononuclear cells and typically with eosinophils. Eosinophilic fasciitis may be separated from another sclerodermatous disorder, linear scleroderma, by its response to systemic corticosteroids. The etiology is unclear but eosinophilic Fasciitis has numerous disease associations. However, it has not previously been associated with renal failure and hemodialysis. Objective: This article reports a case of eosinophilic fasciitis occurring four weeks following the onset of hemodialysis. Methods: The clinical and histologic features confirmed the diagnosis of eosinophilic fasciitis. He vas treated with systemic corticosteroids with good response. Conclusion: This is the first reported patient who developed eosinophilic fasciitis in close temporal relationship with the start of hemodialysis. While eosinophilic fasciitis may be coincidental with a common disorder, namely, renal failure, it is interesting to note that hemodialysis patients often have immune-regulation abnormalities and peripheral eosinophilia. C1 Univ Utah, Hlth Sci Ctr, Dept Dermatol, Salt Lake City, UT 84132 USA. NIH, Bethesda, MD 20892 USA. Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT 84132 USA. RP Florell, SR (reprint author), Univ Utah, Hlth Sci Ctr, Dept Dermatol, 50 N Med Dr, Salt Lake City, UT 84132 USA. NR 26 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1203-4754 J9 J CUTAN MED SURG JI J. Cutan. Med. Surg. PD JAN-FEB PY 2001 VL 5 IS 1 BP 33 EP 36 DI 10.1007/s102270000007 PG 4 WC Dermatology SC Dermatology GA 528NW UT WOS:000174250700007 PM 11281432 ER PT J AU Hoque, ATMS Yamano, S Baccaglini, L Baum, BJ AF Hoque, ATMS Yamano, S Baccaglini, L Baum, BJ TI Using salivary glands as a tissue target for gene therapeutics SO JOURNAL OF DRUG TARGETING LA English DT Article DE gene therapeutics; gene transfer; protein deficiency disorders; protein secretion; salivary glands ID REGULATED SECRETORY PATHWAY; CARBOXYPEPTIDASE-E; PROTEIN SECRETION; GROWTH-HORMONE; IN-VIVO; SORTING RECEPTOR; MAMMALIAN-CELLS; TRANSGENIC MICE; CPE(FAT) MICE; ATT-20 CELLS AB Gene transfer offers a potential way to correct local and systemic protein deficiency disorders by using genes as drugs, so called gene therapeutics. Salivary glands present an interesting target site for gene therapeutic applications. Herein, we review proofs of concept achieved for salivary glands with in vivo animal models. In that context we discuss problems (general and salivary tissue-specific) that limit immediate clinical use for this application of gene transfer. Ongoing efforts, however, suggest that salivary glands may be suitable as gene therapeutic target sites for drug delivery in the near future. C1 Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. OI Yamano, Seiichi/0000-0003-2056-4359 NR 68 TC 6 Z9 6 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK,, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-186X J9 J DRUG TARGET JI J. Drug Target. PY 2001 VL 9 IS 6 BP 485 EP 494 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 513ZC UT WOS:000173397300009 PM 11822820 ER PT J AU Fiuza, C Suffredini, AF AF Fiuza, C Suffredini, AF TI Human models of innate immunity: local and systemic inflammatory responses SO JOURNAL OF ENDOTOXIN RESEARCH LA English DT Article; Proceedings Paper CT 6th Conference of the International-Endotoxin-Society CY AUG 24-27, 2000 CL PARIS, FRANCE SP Int Endotoxin Soc ID LOWER RESPIRATORY-TRACT; INTRAVENOUS ENDOTOXIN; GRAIN DUST; ANTIINFLAMMATORY THERAPY; INHALATION AB We review human studies where different body sites (e.g. systemic-intravenous and local-skin or lung) are exposed to small amounts of bacterial components as a means to study innate immunity in vivo. Intravenous endotoxin administration is widely used to assess systemic inflammatory responses, and these have many similarities to those seen in early sepsis. While blood levels of cytokines, activated inflammatory cells, and stress hormones rise acutely, the alveolar space remains relatively protected from these inflammatory responses. Skin blister windows provide a means to study local neutrophil exudation without systemic inflammatory responses, and has been used to characterize defects in neutrophil transmigration. Recently, skin blister windows have been adapted to study phagocytic cell function in response to bacterial antigens in patients with cirrhosis. Inhalation of endotoxin leads to pulmonary inflammation with increases in broncho-alveolar lavage neutrophils and cytokines and mild systemic responses. Whole lung exposure to endotoxin provides a means to study the pathogenesis of occupational lung disease. These three models are important methods to study innate immune responses and their regulatory mechanisms in normal and diseased states. C1 NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Suffredini, AF (reprint author), NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bldg 10,Room 7D-43,10 Ctr Dr, Bethesda, MD 20892 USA. NR 19 TC 37 Z9 39 U1 1 U2 1 PU MANEY PUBLISHING PI LEEDS PA HUDSON RD, LEEDS LS9 7DL, ENGLAND SN 0968-0519 J9 J ENDOTOXIN RES JI J. Endoxtin Res. PY 2001 VL 7 IS 5 BP 385 EP 388 DI 10.1179/096805101101532963 PG 4 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA 508LQ UT WOS:000173090600007 PM 11753208 ER PT J AU Fu, PP Chou, MW Xia, Q Yang, YC Yan, J Doerge, DR Chan, PC AF Fu, PP Chou, MW Xia, Q Yang, YC Yan, J Doerge, DR Chan, PC TI Genotoxic pyrrolizidine alkaloids and pyrrolizidine alkaloid N-oxides - Mechanisms leading to DNA adduct formation and tumorigenicity SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE pyrrolizidine alkaloids; mechanism; tumorigenicity; human exposure; DNA adducts ID VENO-OCCLUSIVE DISEASE; FLAVIN-CONTAINING MONOOXYGENASE; RAGWORT SENECIO-JACOBAEA; PROTEIN CROSS-LINKS; S-PHASE SYNTHESIS; RAT-LIVER; CARCINOGENIC ACTIVITY; GUINEA-PIG; MEDICINAL-PLANTS; IN-VITRO AB Plants that contain pyrrolizidine alkaloids and pyrrolizidine alkaloid N-oxides are widely distributed in the world. These plants are probably the most common poisonous plants affecting livestock, wildlife, and humans. Although pyrrolizidine alkaloids have been shown to be genotoxic, including tumorigenic in experimental animals, the mechanisms of tumor formation have not been fully understood. Our recent studies on riddelliine, riddelline N-oxide, and dehydroretronecine (DHR) provided evidence suggesting that pyrrolizidine alkaloids and pyrrolizidine alkaloid N-oxides induce tumors via a genotoxic mechanism, and that tumorigenicity is mediated by a set of eight DHR-derived DNA adducts. This mechanism may be general to other carcinogenic pyrrolizidine alkaloids and may also be responsible for the other genotoxicities of pyrrolizidine alkaloids, including mutagenicity and teratogenicity. It is hypothesized that these DHR-derived DNA adducts are potential biomarkers of pyrrolizidine alkaloid tumorigenicity. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 165 TC 38 Z9 40 U1 1 U2 17 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2001 VL 19 IS 2 BP 353 EP 385 DI 10.1081/GNC-100107580 PG 33 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 537VY UT WOS:000174781400002 ER PT J AU Vestereng, VH Kovacs, JA AF Vestereng, VH Kovacs, JA TI Recombinant CD40 ligand administration does not decrease intensity of Pneumocystis carinii infection in scid mice SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article; Proceedings Paper CT 7th International Workshop on Opportunistic Protists CY JUN 13-16, 2001 CL CINCINNATI, OHIO SP Soc Protozoologists, Univ Cincinnati AB X-linked Hyper IgM Syndrome (HIM) is a rare congenital immunodeficiency recently demonstrated to be caused by a mutation in the gene encoding CD40 ligand. These patients are susceptible to Pneumocystis carinii pneumonia, which implies an important role for CD40L in host defense against P. carinii. In this study we undertook to investigate whether treatment of P. carinii infected scid mice with murine recombinant CD40 ligand trimer (muCD40L) for 21 days would facilitate clearance of the organisms. We found no significant difference in organism burden in treated compared to control animals. Therefore in this model treatment with muCD40L alone is ineffective in clearing P. carinii infection. C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Kovacs, JA (reprint author), NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PY 2001 SU S BP 153S EP 154S PG 2 WC Microbiology SC Microbiology GA 531MN UT WOS:000174419300065 ER PT J AU Valenzuela, JG Belkaid, Y Rowton, E Ribeiro, JMC AF Valenzuela, JG Belkaid, Y Rowton, E Ribeiro, JMC TI The salivary apyrase of the blood-sucking sand fly Phlebotomus papatasi belongs to the novel Cimex family of apyrases SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE apyrase; salivary gland; haematophagy; bed bug; Cimex lectularius ID MOSQUITO ANOPHELES-ALBIMANUS; RHODNIUS-PROLIXUS; AEDES-AEGYPTI; LUTZOMYIA-LONGIPALPIS; PURIFICATION; CLONING; NITROPHORIN; LECTULARIUS; ATPASES; BINDING AB Apyrases are enzymes that hydrolyze nucleotide di- and triphosphates to orthophosphate and mononucleotides, At least two families of enzymes, belonging to the 5'-nucleotidase and to the actin/heat shock 70/sugar kinase superfamily, have evolved independently to serve the apyrase reaction. Both families require either Ca2+ or Mg2+ for their action. A novel apyrase enzyme sequence, with no homology to any other known protein sequence, was found recently in the salivary glands of the hematophagous bed bug Cimex lectularius. This enzyme functions exclusively with Ca2+. Here, we report the finding of a cDNA similar to that of the C. lectularius salivary apyrase isolated from a salivary gland cDNA library of Phlebotomus papatasi, Transfection of insect cells with the P. papatasi salivary gland apyrase cDNA resulted in the secretion of a Ca2+-dependent apyrase whose activity was indistinguishable from that in salivary homogenates of P. papatasi. Homologous sequences were found in humans, in another sand fly (Lutzomyia longipalpis), in the fruit fly Drosophila melanogaster, in the nematode Caenorhabditis elegans and in the protozoan Cryptosporidium parvum, indicating that this family of enzymes is widespread among animal species. C1 NIAID, Sect Med Entomol, Parasit Dis Lab, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Entomol, Washington, DC 20307 USA. RP Ribeiro, JMC (reprint author), NIAID, Sect Med Entomol, Parasit Dis Lab, Bldg 4,Room 126,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. RI Rowton, Edgar/A-1975-2011; Rowton, Edgar/A-4474-2012; OI Rowton, Edgar/0000-0002-1979-1485; Ribeiro, Jose/0000-0002-9107-0818 NR 34 TC 84 Z9 85 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD JAN PY 2001 VL 204 IS 2 BP 229 EP 237 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 397VB UT WOS:000166717400006 PM 11136609 ER PT J AU Dolensky, B Takeuchi, Y Cohen, LA Kirk, KL AF Dolensky, B Takeuchi, Y Cohen, LA Kirk, KL TI Synthesis of 4,5-difluoroimidazole SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article DE photochemical Schiemann reaction fluoroimidazoles AB 5-Fluoroimidazole-4-carboxylic acid ethyl ester was converted to the corresponding hydrazide. Oxidation of the hydrazide to the carbonyl azide and Curtius rearrangement in t-butyl alcohol produced 4-t-butyloxycarbonylamino-5-fluoroimidazole. Dissolution of the t-butyl carbamate in 50% HBF4, in situ diazotation of the resulting amine, and irradiation produced the target compound. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Toyama Med & Pharmaceut Univ, Fac Pharmaceut Sci, Toyama, Japan. RP Kirk, KL (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 3 TC 6 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD JAN PY 2001 VL 107 IS 1 BP 147 EP 148 DI 10.1016/S0022-1139(00)00385-7 PG 2 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA 397CR UT WOS:000166676200025 ER PT J AU Jeong, DH Lee, SJ Lee, JH Bae, IH Jeong, KS Jang, JJ Lim, IK Kim, MR Lee, MJ Lee, YS AF Jeong, DH Lee, SJ Lee, JH Bae, IH Jeong, KS Jang, JJ Lim, IK Kim, MR Lee, MJ Lee, YS TI Subcellular redistribution of protein kinase C isozymes is associated with rat liver cirrhotic changes induced by carbon tetrachloride or thioacetamide SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE CCl4; thioacetamide; rat-liver cirrhosis; protein kinase C isozymes; subcellular distribution ID HEPATOCARCINOGENESIS; DIFFERENTIATION; EXPRESSION; COLLAGEN; ISOFORMS; CANCER AB Background and Aims: Protein kinase C (PKC) plays a key role in the alteration of signal transduction in the liver, which may contribute to the development of liver cirrhosis. The aim of the present study was to examine the subcellular redistribution of PKC isozymes in rat liver cirrhosis, which is induced by two different cirrhotic chemical agents, carbon tetrachloride (CCl4) and thioacetamide (TAA). Methods and Results: Thioacetamide and CCl4 were administered to rats for 8 and 30 weeks, respectively before rats were killed and autopsies performed at 9, 20 and 30 weeks later. The TAA induced a fibrotic pattern in the liver that differed from that produced by CCl4, notably in the formation of fibrous connective tissue and the proliferation of bile ductule cells. Cholangiofibrosis and clear-cell foci were also observed in TAA-treated rats at 30 weeks. Histological examination revealed that severe cirrhotic changes were present 9 weeks after the commencement of CCl4 treatment and 30 weeks after TTA treatment. Discussion: When the subcellular redistribution of PKC isozymes (PKC alpha, -beta1, -delta, and -epsilon) was examined, all the PKC isozymes in CCl4-treated rats were found to be translocated to the membrane fraction, which may mean PKC activation, and then downregulated by proteolytic degradation after 9 weeks of treatment, which coincided with peak cirrhotic changes. All rats treated with CCl4 recovered to the control level after 20 weeks of treatment, In the case of TAA-treated rats, PKC isozymes were translocated to the particulate fraction of the liver after 9 weeks of treatment and this persisted in most of the rats for the duration of the experiment. Conclusions: From these results, it would appear that PKC translocation preceded morphologic changes, and that an altered subcellular distribution of the PKC isozyme may be associated with the response to liver damage and carcinogenesis. (C) 2001 Blackwell Science Asia Pty Ltd. C1 Korea Canc Ctr Hosp, Lab Radiat Effect, Seoul 139706, South Korea. Kyungpook Natl Univ, Coll Vet Med, Daegue, South Korea. Korea Canc Ctr Hosp, Lab Expt Pathol, Seoul 139706, South Korea. NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA. Seoul Natl Univ, Coll Med, Canc Res Ctr, Dept Pathol, Seoul, South Korea. Ajou Univ, Sch Med, Dept Biochem & Mol Biol, Suwon 441749, South Korea. RP Lee, YS (reprint author), Korea Canc Ctr Hosp, Lab Radiat Effect, 215-4 Gongneung Dong, Seoul 139706, South Korea. RI Jang, JaJune/F-6647-2011; Seoul National University, Pathology/B-6702-2012 NR 21 TC 13 Z9 14 U1 1 U2 2 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD JAN PY 2001 VL 16 IS 1 BP 34 EP 40 DI 10.1046/j.1440-1746.2001.02364.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 414PG UT WOS:000167674800006 PM 11206314 ER PT J AU Baccaglini, L Hoque, ATMS Wellner, RB Goldsmith, CM Redman, RS Sankar, V Kingman, A Barnhart, KM Wheeler, CJ Baum, BJ AF Baccaglini, L Hoque, ATMS Wellner, RB Goldsmith, CM Redman, RS Sankar, V Kingman, A Barnhart, KM Wheeler, CJ Baum, BJ TI Cationic liposome-mediated gene transfer to rat salivary epithelial cells in vitro and in vivo SO JOURNAL OF GENE MEDICINE LA English DT Article DE transfection; cationic lipid; salivary gland ID PLASMID DNA; IN-VIVO; NASAL EPITHELIUM; CYSTIC-FIBROSIS; GROWTH-HORMONE; GLANDS; ADENOVIRUS; EXPRESSION; DELIVERY; MICE AB Background Previously we have shown that gene transfer to salivary gland epithelial cells readily occurs via recombinant adenoviruses, although the response is short-lived and results in a potent host immune response. The aim of the present study was to assess the feasibility of using cationic liposomes to mediate gene transfer to rat salivary cells in vitro and in vivo. Methods Initially, for transfection in vitro, we used two cationic liposome formulations (GAP-DLRIE/DOPE and DOSPA/DOPE) complexed with plasmid encoding human growth hormone (hGH) as a reporter gene. Thereafter, using GAP-DLRIE/DOPE, plasmids were transferred to rat salivary glands in vivo, and hGH levels measured in saliva, serum and gland extracts. Results Under optimal conditions, transfection of rat submandibular glands (SMGs) was consistently observed. Approximately 95% of the cells transfected with a plasmid encoding beta -galactosidase were acinar cells. Maximal hGH expression was obtained during the first 48 h post-transfection using a plasmid encoding the hGH cDNA and complexed with GAP-DLRIE/ DOPE. hGH was detected in gland extracts and saliva, and occasionally in serum. No systemic or local gland pathology was consistently or significantly observed. Conclusions The levels of the reporter gene product, hGH, obtained after GAP-DLRIE/DOPE-mediated gene transfer are considerably lower (<0.5%) than those achieved with adenoviral vectors (10(8) PFU). Nonetheless, cationic liposome-mediated gene transfer to salivary glands may be useful for potential therapeutic applications. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. Dept Vet Affairs Med Ctr, Oral Pathol Res Lab, Washington, DC 20422 USA. Natl Inst Dent & Craniofacial Res, Craniofacial Epidemiol & Genet Branch, NIH, Bethesda, MD 20892 USA. Vical Inc, San Diego, CA 92121 USA. RP Baum, BJ (reprint author), Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bldg 10,1N113,MSC-1190, Bethesda, MD 20892 USA. NR 36 TC 35 Z9 35 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD JAN-FEB PY 2001 VL 3 IS 1 BP 82 EP 90 DI 10.1002/1521-2254(2000)9999:9999<::AID-JGM151>3.0.CO;2-X PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 403MK UT WOS:000167046900008 PM 11269339 ER PT J AU Podolski, J Byrski, T Zajaczek, S Druck, T Zimonjic, DB Popescu, NC Kata, G Borowka, A Gronwald, J Lubinski, J Huebner, K AF Podolski, J Byrski, T Zajaczek, S Druck, T Zimonjic, DB Popescu, NC Kata, G Borowka, A Gronwald, J Lubinski, J Huebner, K TI Characterization of a familial RCC-associated t(2;3)(q33;q21) chromosome translocation SO JOURNAL OF HUMAN GENETICS LA English DT Article DE clear cell RCC; familial renal cancer; constitutional chromosome translocation; FRA2G; BAC contigs; positional cloning ID CELL RENAL CARCINOMAS; TUMOR-SUPPRESSOR GENE; COMMON FRAGILE SITES; FHIT EXPRESSION; SHORT ARM; CANCER; APHIDICOLIN; DELETION; 3P14.2; LOCUS AB A Polish family was identified in which multifocal clear cell renal carcinoma segregated with a balanced constitutional chromosome translocation, t(2;3)(q33;q21), similar to the renal cell cancer-associated t(2;3)(q35;q21) reported in a Dutch family. Bacterial artificial chromosome (BAC) contigs encompassing the 2q and 3q breakpoints were constructed and BACs crossing the breakpoints were partially sequenced. All known regional markers, genes, and expressed sequence tags (ESTs) were mapped relative to the contigs, as well as to the breakpoint sequences. Two single ESTs mapped within the 2q breakpoint BAC, whereas the repeat-rich 3q breakpoint region was gene poor. Physical mapping suggested that the 3q break was in 3q13, possibly near the border with 3q21. Physical mapping illustrated that the 2q break was closely telomeric to the 2q31 FRA2G site, consistent with the G-band assignment. Characterization of full-length cDNAs for the ESTs near the 2q break will determine if a gene(s) is altered by this familial translocation. C1 Kimmel Canc Ctr, BLSB, Philadelphia, PA 19107 USA. Tech Univ Szczecin, Dept Human Ecol, PL-71065 Szczecin, Poland. Pomeranian Acad Med, Dept Genet & Pathol, Hereditary Canc Ctr, Szczecin, Poland. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. Med Ctr Postgrad Educ, Dept Urol, PL-01813 Warsaw, Poland. RP Huebner, K (reprint author), Kimmel Canc Ctr, BLSB, 233 S 10th St,Room 1008, Philadelphia, PA 19107 USA. RI BYRSKI, Tomasz/I-2844-2014; Gronwald, Jacek/A-4576-2017 OI Gronwald, Jacek/0000-0002-3643-2871 FU FIC NIH HHS [F05 TW05426-01, R03 TWO1247]; NCI NIH HHS [CA21124, CA56036] NR 31 TC 17 Z9 17 U1 0 U2 0 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 1434-5161 J9 J HUM GENET JI J. Hum. Genet. PY 2001 VL 46 IS 12 BP 685 EP 693 DI 10.1007/s100380170001 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 504TY UT WOS:000172873000001 PM 11776380 ER PT J AU Ben-Sasson, SZ Gerstel, R Hu-Li, J Paul, WE AF Ben-Sasson, SZ Gerstel, R Hu-Li, J Paul, WE TI Cell division is not a "clock" measuring acquisition of competence to produce IFN-gamma or IL-4 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4+ T-CELLS; TH2 CELLS; IN-VITRO; INTERLEUKIN-4; DIFFERENTIATION; EXPRESSION; THYMOCYTES; INVITRO; CD4(+); LYMPHOCYTES AB Naive CD4 T cells acquire the potential to produce IFN-gamma and IL-4 by culture in the presence of their cognate Ag, APC, and appropriate cytokines. In this study, we show that commitment to IFN-gamma production on the part of rigorously purified naive CD4 T cells can occur without cell division. Indeed, even entry into S phase is not essential, Moreover, both CD4 and CD4/CD8 thymocytes from TCR-transgenic mice (5CC7 mice) on a Rag2(-/-) background can acquire IFN-gamma -producing capacity when stimulated by peptide, APC, and IL-12. These cells can do so without dividing and some acquire IFN-gamma -producing activity without entry into S phase. Not only is cell division not required for acquisition of cytokine-producing potential, cell populations that have undergone the same numbers of divisions can have quite different proportions of IFN-gamma- or IL-4-producing cells, depending on the duration of priming or, in the case of IL-4, on the concentration of peptide. Thus, cell division is not a clock for the expression of these cytokines. Factors associated with priming conditions including strength of stimulation, duration of priming, and number of divisions each play a role. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Lautenberg Ctr Gen & Tumor Immunol, Jerusalem, Israel. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311, Bethesda, MD 20892 USA. NR 30 TC 61 Z9 61 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2001 VL 166 IS 1 BP 112 EP 120 PG 9 WC Immunology SC Immunology GA 385PG UT WOS:000166012400016 PM 11123283 ER PT J AU Kim, SH Reznikov, LL Stuyt, RJL Selzman, CH Fantuzzi, G Hoshino, T Young, HA Dinarello, CA AF Kim, SH Reznikov, LL Stuyt, RJL Selzman, CH Fantuzzi, G Hoshino, T Young, HA Dinarello, CA TI Functional reconstitution and regulation of IL-18 activity by the IL-18R beta chain SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GAMMA-INDUCING FACTOR; INTERLEUKIN-1 RECEPTOR COMPLEX; BLOOD MONONUCLEAR-CELLS; IFN-GAMMA; INTERFERON-GAMMA; GENE-EXPRESSION; CUTTING EDGE; PROTEIN; CYTOKINE; BINDING AB IL-18 and IL-12 are major IFN-gamma -inducing cytokines but the unique synergism of IL-18 and IL-12 remains unclear. In the human NK cell line NKO, IL-18R alpha, and IL-18R beta are expressed constitutively but IL-18 did not induce IFN-gamma unless IL-12 was present. COS-1 fibroblasts, which produce the chemokine IL-8 when stimulated by IL-1 beta or TNF-alpha, do not respond to IL-18, despite abundant expression of the IL-18R alpha chain. COS-1 cells lack expression of the IL-1R beta chain. The IL-18R beta cDNA was cloned from a human T-B lymphoblast cDNA library and COS-1 cells were transiently transfected with the IL-18R beta chain and a luciferase reporter. In transfected COS-I cells, IL-18 induced IL-8 and luciferase in the absence of IL-12 and independently of IL-1 and TNF. Ab against the IL-18R alpha chain, however, prevented IL-18 responsiveness in COS-1 cells transfected with the IL-18R beta chain, suggesting that both chains be functional. In NKO cells and PBMC, IL-12 increased steady-state mRNA levels of IL-18R alpha and IL-18R beta; the production of IFN-gamma corresponded to IL-12-induced IL-18R alpha and IL-18R beta chains. We conclude that functional reconstitution of the IL-18R beta chain is essential for IL-12-independent proinflammatory activity of IL-18-induced IL-8 in fibroblasts. The synergism of IL-18 plus IL-12 for IFN-gamma production is, in part, due to IL-12 up-regulation of both IL-18R alpha and IL-18R beta chains, although postreceptor events likely contribute to IFN-gamma production. C1 Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Dept Med, Denver, CO 80262 USA. NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Frederick, MD 21702 USA. RP Dinarello, CA (reprint author), Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Dept Med, 4200 E 9th Ave,B168, Denver, CO 80262 USA. RI Young, Howard/A-6350-2008; Fantuzzi, Giamila/A-1758-2009 OI Young, Howard/0000-0002-3118-5111; Fantuzzi, Giamila/0000-0001-5334-0082 FU NCI NIH HHS [CA-46394]; NIAID NIH HHS [AI-15614, AI-2532359] NR 32 TC 60 Z9 63 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2001 VL 166 IS 1 BP 148 EP 154 PG 7 WC Immunology SC Immunology GA 385PG UT WOS:000166012400020 PM 11123287 ER PT J AU Lillard, JW Boyaka, PN Taub, DD McGhee, JR AF Lillard, JW Boyaka, PN Taub, DD McGhee, JR TI RANTES potentiates antigen-specific mucosal immune responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AIRWAY EPITHELIAL-CELLS; RESPIRATORY SYNCYTIAL VIRUS; T-LYMPHOCYTE ACTIVATION; CHOLERA-TOXIN; CHEMOKINE RECEPTOR; IN-VITRO; B-CELLS; BETA-CHEMOKINES; DIFFERENTIAL EXPRESSION; REGULATED EXPRESSION AB RANTES is produced by lymphoid and epithelial cells of the mucosa in response to various external stimuli and is chemotactic for lymphocytes, The role of RANTES in adaptive mucosal immunity has not been studied. To better elucidate the role of this chemokine, we have characterized the effects of RANTES on mucosal and systemic immune responses to nasally coadministered OVA, RANTES enhanced Ag-specific serum Ab responses, inducing predominately anti-OVA IgG2a and IgG3 followed by IgG1 and IgG2b subclass Ab responses. RANTES also increased Ag-specific Ab titers in mucosal secretions and these Ab responses were associated with increased numbers of Ab-forming cells, derived from mucosal and systemic compartments. Splenic and mucosally derived CD4(+) T cells of RANTES-treated mice displayed higher Ag-specific proliferative responses and IFN-gamma, IL-2, IL-5, and IL-6 production than control groups receiving OVA alone. In vitro, RANTES up-regulated the expression of CD28, CD40 ligand, and IL-12R by Ag-activated primary T cells from DO11.10 (OVA-specific TCR-transgenic) mice and by resting T cells in a dose-dependent fashion. These studies suggest that RANTES can enhance mucosal and systemic humoral Ab responses through help provided by Th1- and select Th2-type cytokines as well as through the induction of costimulatory molecule and cytokine receptor expression on T lymphocytes, These effects could serve as a link between the initial innate signals of the host and the adaptive immune system. C1 Univ Alabama, Dept Microbiol, Immunobiol Vaccine Ctr, Birmingham, AL 35294 USA. Morehouse Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30310 USA. NIA, Gerontol Res Ctr, Immunol Lab, Baltimore, MD 21224 USA. RP McGhee, JR (reprint author), Univ Alabama, Dept Microbiol, Immunobiol Vaccine Ctr, 761 BBRB,845 19th St S, Birmingham, AL 35294 USA. FU NIAID NIH HHS [AI 43197, AI 18958]; NIGMS NIH HHS [GM 08248] NR 67 TC 83 Z9 87 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2001 VL 166 IS 1 BP 162 EP 169 PG 8 WC Immunology SC Immunology GA 385PG UT WOS:000166012400022 PM 11123289 ER PT J AU Visintin, A Mazzoni, A Spitzer, JH Wyllie, DH Dower, SK Segal, DM AF Visintin, A Mazzoni, A Spitzer, JH Wyllie, DH Dower, SK Segal, DM TI Regulation of Toll-like receptors in human monocytes and dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INNATE IMMUNITY; SIGNAL-TRANSDUCTION; INTERLEUKIN-1 RECEPTOR; DROSOPHILA TOLL; WALL COMPONENTS; CUTTING EDGE; FAMILY; ACTIVATION; LIPOPOLYSACCHARIDE; RECOGNITION AB A number of pathogens induce immature dendritic cells (iDC) to migrate to lymphoid organs where, as mature DC (mDC), they serve as efficient APC, We hypothesized that pathogen recognition by iDC is mediated by Toll-like receptors (TLRs), and asked which TLRs are expressed during the progression of monocytes to mDC, We first measured mRNA levels for TLRs 1-5 and MD2 (a protein required for TLR4 function) by Northern analysis. For most TLRs, message expression decreased severalfold as monocytes differentiated into IDC, but opposing this trend, TLR3 and MD2 showed marked increases during iDC formation. When iDC were induced to mature with LPS or TNF-alpha, expression of most TLRs transiently increased and then nearly disappeared. Stimulation of iDC, but not mDC, with LPS resulted in the activation of IL-1 receptor-associated kinase, an early component in the TLR signaling pathway, strongly suggesting that LPS signals through a TLR, Surface expression of TLRs 1 and 4, as measured by mAb binding, was very low, corresponding to a few thousand molecules per cell in monocytes, and a few hundred or less in IDC, We conclude that TLRs are expressed in iDC and are involved in responses to at least one pathogen-derived substance, LPS, If TLR4 is solely responsible for LPS signaling in humans, as it is in mice, then its extremely low surface expression implies that it is a very efficient signal transducer in iDC. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Sheffield, Div Mol & Genet Med, Sheffield, S Yorkshire, England. RP Segal, DM (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B36, Bethesda, MD 20892 USA. NR 43 TC 415 Z9 433 U1 2 U2 12 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2001 VL 166 IS 1 BP 249 EP 255 PG 7 WC Immunology SC Immunology GA 385PG UT WOS:000166012400032 PM 11123299 ER PT J AU Faunce, DE Sonoda, KH Stein-Streilein, J AF Faunce, DE Sonoda, KH Stein-Streilein, J TI MIP-2 recruits NKT cells to the spleen during tolerance induction SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNE DEVIATION ACAID; KILLER T-CELLS; ANTERIOR-CHAMBER; DENDRITIC CELLS; ORAL TOLERANCE; B-CELLS; EXPRESSION; CHEMOKINES; ANTIGEN; RECEPTOR AB Peripheral tolerance occurs after intraocular administration of Ag and is dependent on an increase in splenic NKT cells. New data here show that macrophage inflammatory protein-2 (MIP-2) is selectively up-regulated in tolerance-conferring APCs and serves to recruit NKT cells to the splenic marginal zone, where they form clusters with APCs and T cells. In the absence of the high-affinity receptor for MIP-2 las in CXCR2-deficient mice) or in the presence of a blocking Ab to MIP-2, peripheral tolerance is prevented, and Ag-specific T regulatory cells are not generated. Understanding the regulation of lymphocyte traffic during tolerance induction may lead to novel therapies for autoimmunity, graft acceptance, and tumor rejection. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, NEI, Training Program Mol Bases Eye Dis, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Pulm & Crit Care, Boston, MA 02115 USA. RP Stein-Streilein, J (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NEI NIH HHS [EY11983-02, EY07021-02, T32EY07145] NR 34 TC 127 Z9 131 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 JAN 1 PY 2001 VL 166 IS 1 BP 313 EP 321 PG 9 WC Immunology SC Immunology GA 385PG UT WOS:000166012400040 PM 11123307 ER PT J AU Girschick, HJ Grammer, AC Nanki, T Mayo, M Lipsky, PE AF Girschick, HJ Grammer, AC Nanki, T Mayo, M Lipsky, PE TI RAG1 and RAG2 expression by B cell subsets from human tonsil and peripheral blood SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; V(D)J RECOMBINASE ACTIVITY; GERMINAL-CENTERS; GENE-EXPRESSION; LYMPHOCYTES; REARRANGEMENTS; REEXPRESSION; LIGATION; CYCLE AB It has been suggested that B cells acquire the capacity for secondary V(D)J recombination during germinal center (GC) reactions. The nature of these B cells remains controversial. Subsets of tonsil and blood B cells and also individual B cells were examined for the expression of recombination-activating gene (RAG) mRNA, Semiquantitative analysis indicated that RAGI mRNA was present in all tonsil B cell subsets, with the largest amount found in naive B cells. RAG2 mRNA was only found in tonsil naive B cells, centrocytes, and to a lesser extent in centroblasts, Neither RAG1 nor RAG2 mRNA was routinely found in normal peripheral blood B cells. In individual tonsil B cells, RAG1 and RAG2 mRNAs were found in 18% of naive B cells, 22% of GC founder cells, 0% of centroblasts, 13% of centrocytes, and 9% of memory B cells. Individual naive tonsil B cells containing both RAG1 and RAG2 mRNA were activated (CD69(+)). In normal peripheral blood similar to5% of B cells expressed both RAG1 and RAG2. These cells were uniformly postswitch memory B cells as documented by the coexpression of IgG mRNA. These results indicate that coordinate RAG expression is not found in normal peripheral naive B cells but is up-regulated in naive B cells which are activated in the tonsil. With the exception of centroblasts, RAG1 and RAG2 expression can be found in all components of the GC, including postswitch memory B cells, some of which may circulate in the blood of normal subjects. C1 Univ Texas, SW Med Ctr, Harold C Simmons Arthrit Res Ctr, Dept Internal Med, Dallas, TX 75235 USA. RP Lipsky, PE (reprint author), NIAMSD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI 31229]; NIAMS NIH HHS [AR-18550] NR 54 TC 53 Z9 54 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 JAN 1 PY 2001 VL 166 IS 1 BP 377 EP 386 PG 10 WC Immunology SC Immunology GA 385PG UT WOS:000166012400048 PM 11123315 ER PT J AU Bostik, P Mayne, AE Villinger, F Greenberg, KP Powell, JD Ansari, AA AF Bostik, P Mayne, AE Villinger, F Greenberg, KP Powell, JD Ansari, AA TI Relative resistance in the development of T cell anergy in CD4(+) T cells from simian immunodeficiency virus disease-resistant sooty mangabeys SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IL-2 GENE-TRANSCRIPTION; ACTIVE ANTIRETROVIRAL THERAPY; ANTIGEN-PRESENTING CELLS; SIGNAL-REGULATED KINASES; NONHUMAN-PRIMATES; PROTEIN-KINASE; INTERLEUKIN-2 PRODUCTION; CLONAL ANERGY; LYMPHOCYTE ACTIVATION; COSTIMULATORY SIGNAL AB Despite high viral loads, T cells from sooty mangabey (SM) monkeys that are naturally infected with SIV but remain clinically asymptomatic, proliferate and demonstrate normal Ag-specific memory recall CD4(+) T cell responses. In contrast, CD4(+) T cells from rhesus macaques (RM) experimentally infected with SIV lose Ag-specific memory recall responses and develop immunological anergy, To elucidate the mechanisms for these distinct outcomes of lentiviral infection, highly enriched alloreactive CD4(+) T cells from humans, RM, and SM were anergized by TCR-only stimulation (signal 1 alone) and subsequently challenged with anti-CD3/anti-CD28 Abs (signals 1 + 2), Whereas alloreactive CD4(+)T cells from humans and RM became anergized, surprisingly, CD4(+) T cells from SM showed marked proliferation and IL-2 synthesis after restimulation. This resistance to undergo anergy was not secondary to a global deficiency in anergy induction of CD4(+) T cells from SM since incubation of CD4(+) T cells with anti-CD3 alone in the presence of rapamycin readily induced anergy in these cells. The resistance to undergo anergy was reasoned to be due to the ability of CD4(+) T cells from SM to synthesize IL-2 when incubated with anti-CD3 alone. Analysis of phosphorylated kinases involved in T cell activation showed that the activation of CD4(+) T cells by signal 1 in SM elicited a pattern of response that required both signals 1 + 2 in humans and RM, This function of CD4(+) T cells from SM may contribute to the resistance of this species to SIV-induced disease. C1 Emory Univ, Sch Med, Winship Canc Inst, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Bostik, P (reprint author), Emory Univ, Sch Med, Winship Canc Inst, Dept Pathol & Lab Med, 1365B Clifton Rd, Atlanta, GA 30322 USA. FU NIAID NIH HHS [R01 AI27057] NR 85 TC 24 Z9 24 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 JAN 1 PY 2001 VL 166 IS 1 BP 506 EP 516 PG 11 WC Immunology SC Immunology GA 385PG UT WOS:000166012400063 PM 11123330 ER PT J AU Shi, KR Hayashida, K Kaneko, M Hashimoto, J Tomita, T Lipsky, PE Yoshikawa, H Ochi, T AF Shi, KR Hayashida, K Kaneko, M Hashimoto, J Tomita, T Lipsky, PE Yoshikawa, H Ochi, T TI Lymphoid chemokine B cell-attracting chemokine-1 (CXCL13) is expressed in germinal center of ectopic lymphoid follicles within the synovium of chronic arthritis patients SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; FOLLICULAR DENDRITIC CELLS; RHEUMATOID-ARTHRITIS; T-CELLS; CHEMOTACTIC CYTOKINE; LYMPHOTOXIN-ALPHA; TISSUE; OSTEOARTHRITIS; MACROPHAGE; DISEASE AB A unique feature in inflammatory tissue of rheumatoid arthritis (RA) is the formation of ectopic lymphoid aggregates with germinal center (GC)-like structures that can be considered to contribute to the pathogenesis of RA, because local production of the autoantibody, rheumatoid factor, is thought to be a causative factor in tissue damage. However, the factors governing the formation of GC in RA are presently unknown. To begin to address this, the expression of B cell attracting chemokine (BCA-1) (CXCL13), a potent chemoattractant of B cells, was examined in the synovium of patients with RA or with osteoarthritis (OA), Expression of BCA-1 mRNA was detected in all RA samples, but in only one of five OA samples. Lymphoid follicles were observed in four of seven RA samples and in two of eight OA samples, and in most of them BCA-1 protein was detected in GC, BCA-1 was not detected in tissues lacking lymphoid follicles, Notably, BCA-1 was detected predominantly in follicular dendritic cells in GC. CD20-positive B cells were aggregated in regions; of BCA-1 expression, but not T cells or macrophages, These data suggest that BCA-1 produced by follicular dendritic cells may attract B cells and contribute to the formation of GC-like structures in chronic arthritis. C1 Osaka Univ, Sch Med, Dept Orthoped Surg, Osaka 5650871, Japan. NIAMSD, Bethesda, MD 20892 USA. RP Hayashida, K (reprint author), Osaka Univ, Sch Med, Dept Orthoped Surg, 2-2 Yamadaoka, Osaka 5650871, Japan. NR 38 TC 170 Z9 178 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2001 VL 166 IS 1 BP 650 EP 655 PG 6 WC Immunology SC Immunology GA 385PG UT WOS:000166012400082 PM 11123349 ER PT J AU Bownds, S Tong-On, P Rosenberg, SA Parkhurst, M AF Bownds, S Tong-On, P Rosenberg, SA Parkhurst, M TI Induction of tumor-reactive cytotoxic T-lymphocytes using a peptide from NY-ESO-1 modified at the carboxy-terminus to enhance HLA-A2.1 binding affinity and stability in solution SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE NY-ESO-1; cancer testis antigens; HLA-A2.1; cytotoxic T lymphocytes; epitope; immunotherapy ID TESTIS ANTIGEN NY-ESO-1; CANCER-IMMUNOTHERAPY; IMMUNE-RESPONSE; EXPRESSION; MELANOMA; IDENTIFICATION; RESIDUES AB NY-ESO-1 is an attractive candidate tumor antigen for the development of immunotherapies for a wide variety of cancers. It is expressed in multiple types of tumors, but its normal tissue distribution is predominantly limited to the testes and ovaries; furthermore, both humoral and cellular immune responses can be mounted against this protein. Three overlapping HLA-A2.1-restricted T-cell epitopes have been identified within NY-ESO-1. In this investigation, the authors evaluated the in vitro immunogenicity of these peptides. From 2 of 12 HLA-A2.1(+) patients with metastatic melanoma, peptide-reactive cytotoxic T-lymphocytes were generated using either NY-ESO-1:157-167 or NY-ESO-1:157-165 but not NY-ESO-1:155-163. Because NY-ESO-1:157-165 is a 9 amino acid peptide completely contained within NY-ESO-1:157-167, it seemed likely that this peptide was the minimal determinant, and thus it was selected fur continued study. An amino acid substitution of C to V was introduced into NY-ESO-1:157-165 at P9 to attempt to improve its immunogenicity by enhancing its binding affinity to HLA-A2.1 and increasing its stability in solution, because the C residue is readily oxidized, leading to dimerization of the peptide. From 5 of 20 HLA-A2.1(+) patients with metastatic melanoma, NY-ESO-I:157-165(165V) stimulated cytotoxic T-lymphocytes in vitro, which recognized peptide-pulsed target cells and HLA-A2.1(+) NY-ESO-1(+) turner cells, suggesting that this peptide may be clinically valuable for the treatment of patients with NY-ESO-1(+) tumors. C1 NCI, NIH, Surg Branch, Bethesda, MD 20892 USA. RP Parkhurst, M (reprint author), NCI, NIH, Surg Branch, Bldg 10,Room 2B42,900 Rockville Pike, Bethesda, MD 20892 USA. NR 22 TC 36 Z9 36 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JAN-FEB PY 2001 VL 24 IS 1 BP 1 EP 9 DI 10.1097/00002371-200101000-00001 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 394AE UT WOS:000166501200001 PM 11211143 ER PT J AU Chang, E Rosenberg, SA AF Chang, E Rosenberg, SA TI Patients with melanoma metastases at cutaneous and subcutaneous sites are highly susceptible to interleukin-2-based therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Article AB The authors evaluated the records of 371 patients with metastatic melanoma who received treatment with high-dose bolus interleukin-2. Patients with metastases only at cutaneous or subcutaneous sites had a higher objective response rate (50%) than did patients with metastases at these sites plus visceral sites (14%) or patients with metastases at visceral sites only (13%) (p<0.0001). Five patients with disease at cutaneous or subcutaneous sites plus visceral sites experienced regression only at the cutaneous or subcutaneous sites with progression at the visceral sites. Therefore, in the presence of visceral disease, the response rate at cutaneous or subcutaneous sites was only 17% compared with 50% when disease was at the latter sites only (p<0.001). These data suggest that melanoma lesions at cutaneous or subcutaneous sites are highly susceptible targets to interleukin-2-based therapies, but the presence of visceral disease is associated with a significant inhibition of response at cutaneous or subcutaneous sites. C1 NCI, NIH, Surg Branch, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, NIH, Surg Branch, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. NR 3 TC 29 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JAN-FEB PY 2001 VL 24 IS 1 BP 88 EP 90 DI 10.1097/00002371-200101000-00010 PG 3 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 394AE UT WOS:000166501200010 PM 11211152 ER PT J AU Liaw, KL Hildesheim, A Burk, RD Gravitt, P Wacholder, S Manos, MM Scott, DR Sherman, ME Kurman, RJ Glass, AG Anderson, SM Schiffman, M AF Liaw, KL Hildesheim, A Burk, RD Gravitt, P Wacholder, S Manos, MM Scott, DR Sherman, ME Kurman, RJ Glass, AG Anderson, SM Schiffman, M TI A prospective study of human papillomavirus (HPV) type 16 DNA detection by polymerase chain reaction and its association with acquisition and persistence of other HPV types SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CYTOLOGICALLY NORMAL WOMEN; CERVICAL-CANCER; INFECTION; PARTICLES AB Human papillomavirus (HPV)-16 causes about half the cases of cervical cancer worldwide and is the focus of HPV vaccine development efforts. Systematic data are lacking as to whether the prevention of HPV-16 could affect the equilibrium of infection with other HPV types and thus alter the predicted impact of vaccination on the occurrence of cervical neoplasia. Therefore, the associations of HPV-16 detection with subsequent acquisition of other HPV types and with the persistence of concomitantly detected HPV types were examined prospectively among 1124 initially cytologically normal women. Preexisting HPV-16 was generally associated with an increased risk for subsequent acquisition of other types. HPV-16 did not affect the persistence of concomitant infections, regardless of type. These findings suggest that the prevention or removal of HPV-16 is not likely to promote the risk of infection with other types, a theoretical concern with current vaccination efforts. C1 Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. NCI, Dept Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10467 USA. Kaiser Fdn Res Inst, Oakland, CA USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Lab Corp Amer, Res Triangle Pk, NC USA. RP Liaw, KL (reprint author), Univ Pittsburgh, Dept Epidemiol, 513 Parran Hall,130 De Soto St, Pittsburgh, PA 15213 USA. NR 18 TC 176 Z9 184 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2001 VL 183 IS 1 BP 8 EP 15 DI 10.1086/317638 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 385CE UT WOS:000165983400002 PM 11087198 ER PT J AU Celum, CL Buchbinder, SP Donnell, D Douglas, JM Mayer, K Koblin, B Marmor, M Bozeman, S Grant, RM Flores, J Sheppard, HW AF Celum, CL Buchbinder, SP Donnell, D Douglas, JM Mayer, K Koblin, B Marmor, M Bozeman, S Grant, RM Flores, J Sheppard, HW TI Early human immunodeficiency virus (HIV) infection in the HIV network for prevention trials vaccine preparedness cohort: Risk behaviors, symptoms, and early plasma and genital tract virus load SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 12th World AIDS Conference CY JUN 28-JUL 03, 1998 CL GENEVA, SWITZERLAND ID SEXUAL TRANSMISSION; DISEASE PROGRESSION; DRUG-RESISTANCE; VIRAL LOAD; RNA LEVELS; HETEROSEXUAL TRANSMISSION; SEROPOSITIVE INDIVIDUALS; REVERSE-TRANSCRIPTASE; HOMOSEXUAL MEN; CCR-5 DELTA-32 AB Risk behaviors, symptoms, and virologic characteristics were studied among 103 human immunodeficiency virus (HIV) seroconverters in vaccine preparedness cohorts during 1995-1998. Overall, 83% of subjects were men who had sex with men; most reported multiple risk episodes and symptoms (84%, greater than or equal to1 symptom) during seroconversion. Acute HIV was diagnosed in only 8 of 50 who sought medical care. Median initial pretreatment plasma virus load was 25,800 copies/mL (range, undetectable-262,000 copies/mL) a mean of 4 months after seroconversion, and 9.7% had nucleoside-associated mutations; none had multidrug resistance. Semen virus load was more variable, 1.3 log(10) lower and modestly correlated (r = .28; 95% confidence interval, 0.16-0.42) with plasma among untreated men. When the plasma RNA level was <5000 copies/mL, 32% of untreated men, 13% on nucleoside regimens, and 7% on protease inhibitor-containing regimens had detectable seminal RNA. Acute HIV was seldom diagnosed, representing missed opportunities for early treatment and prevention. Most subjects had several relatively stable virus loads before initiation of antiretrovirals, indicating feasibility of assessing HIV vaccines on virus set point in efficacy trials. C1 Univ Washington, Harborview Med Ctr, HIV Prevent Trials Unit, Seattle, WA 98104 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco Dept Publ Hlth, San Francisco, CA 94143 USA. Calif Dept Hlth Serv, Viral & Rickettsial Dis Lab, Berkeley, CA 94704 USA. Denver Dept Publ Hlth, Denver, CO USA. Fenway Community Hlth Ctr, Boston, MA USA. Brown Univ, Mem Hosp, Boston, MA USA. Brown Univ, Miriam Hosp, Boston, MA USA. ABT Associates Inc, Cambridge, MA 02138 USA. New York Blood Ctr, New York, NY 10021 USA. NYU, Sch Med, New York, NY USA. NIAID, Div AIDS, Bethesda, MD 20892 USA. RP Celum, CL (reprint author), Univ Washington, Harborview Med Ctr, HIV Prevent Trials Unit, Box 359927,325 9th Ave, Seattle, WA 98104 USA. OI Marmor, Michael/0000-0001-6605-2661; Donnell, Deborah/0000-0002-0587-7480 FU NIAID NIH HHS [AI-35176, AI-45200, AI-45202] NR 82 TC 54 Z9 55 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2001 VL 183 IS 1 BP 23 EP 35 DI 10.1086/317658 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 385CE UT WOS:000165983400004 PM 11106536 ER PT J AU Imamichi, H Crandall, KA Natarajan, V Jiang, MK Dewar, RL Berg, S Gaddam, A Bosche, M Metcalf, JA Davey, RT Lane, HC AF Imamichi, H Crandall, KA Natarajan, V Jiang, MK Dewar, RL Berg, S Gaddam, A Bosche, M Metcalf, JA Davey, RT Lane, HC TI Human immunodeficiency virus type 1 quasi species that rebound after discontinuation of highly active antiretroviral therapy are similar to the viral quasi species present before initiation of therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT XIIIth International AIDS Conference CY JUL 09-14, 2000 CL DURBAN, SOUTH AFRICA ID HIV-1; INFECTION; REPLICATION; DNA; INDINAVIR; PLASMA; CELLS; PERSISTENCE; RESERVOIRS; SEQUENCES AB In an effort to identify the sources of the viruses that emerge after discontinuation of therapy, analyses of human immunodeficiency virus (HIV) quasi species were done for 3 patients with sustained levels of HIV RNA of <50 copies/mL for 1-3 years. The sequences found in the rebounding plasma virus were closely related to those of the actively replicating form of viruses present before the initiation of combination therapy. All quasi species found in the rebounding plasma virus were also present in proviral DNA, cell-associated RNA in peripheral blood mononuclear cells (PBMC), and virion RNA derived from PBMC coculture during periods when plasma HIV RNA levels were <50 copies/mL. These findings suggest that the rapid resurgence of plasma viremia observed after discontinuation of therapy and the viruses cocultured from PBMC are derived from a relatively stable pool of the replicating form of virus rather than from activation of a previously latent pool. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp Frederick, Frederick Canc Res & Dev Ctr, Bethesda, MD 20892 USA. Brigham Young Univ, Dept Zool, Provo, UT 84602 USA. RP Lane, HC (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Rm 11S231, Bethesda, MD 20892 USA. OI Crandall, Keith/0000-0002-0836-3389 FU NCI NIH HHS [N01-CO-5660] NR 35 TC 87 Z9 87 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2001 VL 183 IS 1 BP 36 EP 50 DI 10.1086/317641 PG 15 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 385CE UT WOS:000165983400005 PM 11106537 ER PT J AU Singer, SM Elmendorf, HG Conrad, JT Nash, TE AF Singer, SM Elmendorf, HG Conrad, JT Nash, TE TI Biological selection of variant-specific surface proteins in Giardia lamblia SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Woods Hole Immunoparasitology Meeting CY SEP 27-30, 1997 CL WOODS HOLE, MASSACHUSETTS ID ANTIGENIC VARIATION; TRYPANOSOMA-BRUCEI; INFECTIONS; ISOLATE; GENE; MICE; EXPRESSION; ANTIBODIES; VIRULENCE; GERBILS AB Immune evasion is frequently cited as the main reason for antigenic variation in pathogenic microorganisms. To better understand the role of switching of variant-specific surface proteins (VSPs) in Giardia lamblia-host interactions, antigenic variation during infections of mice and gerbils was examined, using clones that predominantly expressed unique VSPs. As expected, VSPs were selected against during infections of immunocompetent hosts. In contrast, in immunodeficient hosts, some VSPs were selected for and others were selected against. These diverse patterns of selection demonstrate that there are host-VSP interactions that exert both positive and negative selective pressures on parasites, independent of the adaptive immune response. Furthermore, selection was dependent on both the particular VSP and the host. Thus, the large number of VSP genes in G. lamblia may allow the parasite to infect multiple different hosts, and antigenic variation could be a mechanism to expand the parasite's host range. C1 NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Nash, TE (reprint author), NIH, Parasit Dis Lab, 9000 Rockville Pike,Bldg 4,Rm B1-31, Bethesda, MD 20892 USA. NR 41 TC 24 Z9 26 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2001 VL 183 IS 1 BP 119 EP 124 DI 10.1086/317659 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 385CE UT WOS:000165983400015 PM 11087204 ER PT J AU Womack, C Roth, W Newman, C Rissing, JP Lovell, R Haburchak, D Essex, M Bond, VC AF Womack, C Roth, W Newman, C Rissing, JP Lovell, R Haburchak, D Essex, M Bond, VC TI Identification of non-B human immunodeficiency virus type 1 subtypes in rural Georgia SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GENETIC SUBTYPES; UNITED-STATES; DIVERSITY; TRENDS; HIV AB As part of an ongoing molecular epidemiological investigation of human immunodeficiency virus type 1 (HIV-1) in rural Georgia, the 50 half of reverse transcriptase (RT) genotypes from 30 patients was sequenced and phylogenetically analyzed. Two patients, GA132 and GA169, were infected with pol sequences of non-B subtype origin that were found to cluster phylogenetically with subtype A-E of Thai origin. Sliding window bootstrap analysis of GA169 showed clear evidence of A/B recombination within the pol gene segment, whereas in the other patient, GA132, no break point within RT could be identified. Interestingly, pairwise comparisons between these 2 patients' C2-V3 env region revealed a 13.5% divergence. However, similar comparisons within the non-B pol segments yielded a 1.23% nucleotide divergence, which suggests a complex phylogenetic and epidemiological history of the subtype A pol genotype in this region. These data demonstrate an increasing diversity of HIV-1 subtypes and the potential emergence of previously unidentified HIV-1 A-E/B recombinants in the rural United States. C1 Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, AIDS Inst, Boston, MA 02115 USA. Morehouse Sch Med, Dept Biochem, Atlanta, GA 30310 USA. Med Coll Georgia, Dept Med, Augusta, GA 30912 USA. RP Womack, C (reprint author), NIAID, Immunoregulat Lab, NIH, 10 Ctr Dr,Bldg 10,Rm 6A11, Bethesda, MD 20892 USA. FU NCRR NIH HHS [G12-RR03034] NR 14 TC 16 Z9 16 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2001 VL 183 IS 1 BP 138 EP 142 DI 10.1086/317649 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 385CE UT WOS:000165983400019 PM 11106540 ER PT J AU Wilbur, WJ AF Wilbur, WJ TI Global term weights for document retrieval learned from TREC data SO JOURNAL OF INFORMATION SCIENCE LA English DT Article ID INFORMATION-RETRIEVAL; PROBABILISTIC MODEL AB A key element in modern text retrieval systems is the weighting of individual words for importance. Early in the development of document retrieval methods it was recognized that performance could be improved if weights were based at least in part on the frequencies of individual terms in the database. This observation led investigators to propose inverse document frequency weighting, which has become the most commonly used approach. Inverse document frequency weighting can be given some justification based on probabilistic arguments. However, many different formulas have been tried and it is difficult to distinguish between these on a purely theoretical basis. Witten, Moffat and Bell, have proposed a monotonicity condition as fundamental: 'a term that appears in many documents should not be regarded as more important than a term that appears in a few'. Based on this monotonicity assumption and probabilistic arguments we show here how the TREC data can be used to learn ideal global weights. Using cross-validation we show that these weights are a modest but statistically significant improvement over IDF weights. One conclusion is that IDF weights are close to optimal within the probabilistic assumptions that are commonly made. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Wilbur, WJ (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,Rm 8S806,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 24 TC 1 Z9 1 U1 0 U2 1 PU BOWKER-SAUR PI E GRINSTEAD PA WINDSOR COURT, EAST GRINSTEAD HOUSE, E GRINSTEAD RH19 1XA, W SUSSEX, ENGLAND SN 0165-5515 J9 J INFORM SCI JI J. Inf. Sci. PY 2001 VL 27 IS 5 BP 303 EP 310 DI 10.1177/016555150102700501 PG 8 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA 499QH UT WOS:000172581500002 ER PT J AU Brady, RO AF Brady, RO TI Fabray disease: natural course and new therapeutic options - Commentary SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Editorial Material C1 NINCDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Brady, RO (reprint author), NINCDS, Dev & Metab Neurol Branch, NIH, Bldg 10 Room 3D04,10 Ctr DR MSC 1260, Bethesda, MD 20892 USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PY 2001 VL 24 SU 2 BP 11 EP 12 DI 10.1023/A:1012495018288 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 494QD UT WOS:000172295600003 ER PT J AU Schiffmann, R AF Schiffmann, R TI Natural history of Fabry disease in males: preliminary observations SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article; Proceedings Paper CT International Symposium on Lysosomal Storage Diseases (LSDs) CY APR, 2001 CL SEVILLE, SPAIN AB A large cohort of patients with Fabry disease is being studied to determine the natural history of the disease and how this relates to the specific mutation involved and the amount of residual alpha -galactosidase A activity. To date, we have investigated the progression of cerebral lesions and stroke, as identified by magnetic resonance imaging, and renal disease. Results have shown that cerebral lesions do not appear until 23 years of age, but are present in all patients by 55 years of age. The peak onset of proteinuria occurred in the fourth decade, and the peak onset of chronic renal insufficiency and end-stage renal disease occurred in the fifth decade of life. Renal outcome was related to the type of mutation and residual enzyme activity. Data from these studies in untreated patients will be important when assessing the long-term efficacy of enzyme replacement therapy. C1 NINCDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Schiffmann, R (reprint author), NINCDS, Dev & Metab Neurol Branch, NIH, Bldg 10 Room 3D04,10 Ctr DR MSC 1260, Bethesda, MD 20892 USA. NR 2 TC 20 Z9 22 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PY 2001 VL 24 SU 2 BP 15 EP 17 DI 10.1023/A:1012499119196 PG 3 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 494QD UT WOS:000172295600005 PM 11758674 ER PT J AU Brady, RO Murray, GJ Moore, DF Schiffmann, R AF Brady, RO Murray, GJ Moore, DF Schiffmann, R TI Enzyme replacement therapy in Fabry disease SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article; Proceedings Paper CT International Symposium on Lysosomal Storage Diseases (LSDs) CY APR, 2001 CL SEVILLE, SPAIN ID ALPHA-GALACTOSIDASE; GAUCHER DISEASE; GLUCOCEREBROSIDASE; DEFICIENCY AB Recent clinical trials have demonstrated that enzyme replacement therapy with alpha -galactosidase A (alpha -Gal A) constitutes a major clinical advance in the treatment of patients with Fabry disease. This new therapeutic approach has been shown to be well tolerated and effective in reducing levels of the storage product globo-triaosylceramide and in normalizing many of the debilitating manifestations of the disorder. A double-blind placebo-controlled trial in 26 hemizygous male patients showed that agalsidase alfa (human alpha -Gal A) significantly reduced neuropathic pain (p = 0.02), increased creatinine clearance (p = 0.02), improved glomerular histology, reduced the QRS interval on electrocardiography and increased weight gain. Positron emission tomography also revealed normalization of cerebrovascular flow. After the 6-month controlled period, all patients were given agalsidase alfa for a further 12 months. At the end of this period, all patients had a decrease in neuropathic pain, and there was a significant improvement in their ability to sense heat and cold. In addition, renal function stabilized, even in patients with renal insufficiency at the onset of treatment, and patients reported a normalization of sweating and improvements in their level of energy and sense of well-being. These findings show that enzyme replacement therapy offers promise as an effective management strategy for patients with Fabry disease. C1 NINCDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Brady, RO (reprint author), NINCDS, Dev & Metab Neurol Branch, NIH, Bldg 10 Room 3D04,10 Ctr DR MSC 1260, Bethesda, MD 20892 USA. NR 16 TC 39 Z9 40 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PY 2001 VL 24 SU 2 BP 18 EP 24 DI 10.1023/A:1012451320105 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 494QD UT WOS:000172295600006 PM 11758675 ER PT J AU Enns, GM Seppala, R Musci, TJ Weisiger, K Ferrell, LD Wenger, DA Gahl, WA Packman, S AF Enns, GM Seppala, R Musci, TJ Weisiger, K Ferrell, LD Wenger, DA Gahl, WA Packman, S TI Clinical course and biochemistry of sialuria SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID N-ACETYLNEURAMINIC ACID; SIALIC-ACID; FIBROBLASTS; DISEASE; 2-EPIMERASE; EGRESS AB Sialuria is a rare inborn error of metabolism in which excessive free sialic acid (N-acetylneuraminic acid, NeuAc) is synthesized. A defect in the feedback inhibition of UDP-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase by the end-product of the sialic acid synthetic pathway, CMP-NeuAc, is the mechanism underlying this overproduction. Recent evidence suggests that sialuria is an autosomal dominant disorder. Only five patients have been documented to have such an enzymatic defect. We report a longitudinal study of one of the original sialuria patients, to age 11 years. Although he has coarse features and massive hepatomegaly, he has shown normal growth and relatively normal development. Pulmonary function testing showed minimal small airway obstruction. At 11 years, he developed intermittent abdominal pain and transient transaminase elevation above his baseline. Sialuria should be considered in the differential diagnosis of a patient with a phenotype suggestive of a mucopolysaccharidosis or oligosaccharidosis in the absence of developmental regression or prominent dysostosis multiplex. We recommend close monitoring of liver and pulmonary function in sialuria patients. C1 Stanford Univ, Dept Pediat, Div Med Genet, Stanford, CA 94305 USA. Univ Calif San Francisco, Dept Pediat, Div Med Genet, San Francisco, CA 94143 USA. NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Univ Oulu, Dept Pathol, Oulu, Finland. Univ Calif San Francisco, Dept Obstet & Gynecol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Neurol, Philadelphia, PA 19107 USA. RP Enns, GM (reprint author), Stanford Univ, Dept Pediat, Div Med Genet, 300 Pasteur Dr,H-315, Stanford, CA 94305 USA. FU NCRR NIH HHS [MO1RR01271]; NIGMS NIH HHS [GM07085] NR 17 TC 12 Z9 12 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PY 2001 VL 24 IS 3 BP 328 EP 336 DI 10.1023/A:1010588115479 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 443GA UT WOS:000169331400002 PM 11486897 ER PT J AU Wyse, DG Love, JC Yao, Q Carlson, MD Cassidy, P Greene, LH Martins, JB Ocampo, C Raitt, MH Schron, E Stamato, NJ Olarte, A AF Wyse, DG Love, JC Yao, Q Carlson, MD Cassidy, P Greene, LH Martins, JB Ocampo, C Raitt, MH Schron, E Stamato, NJ Olarte, A CA AVID Investigators TI Atrial fibrillation: A risk factor for increased mortality - An AVID registry analysis SO JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY LA English DT Article; Proceedings Paper CT 71st Scientific Session of the American-Heart-Association Meeting CY NOV 08-12, 1998 CL DALLAS, TEXAS SP Amer Heart Assoc DE atrial fibrillation; mortality; ventricular arrhythmias; antiarrhythmic drugs ID HEART-FAILURE; PROGNOSIS; STROKE AB Emerging evidence suggests that atrial fibrillation is not a benign arrhythmia. It is associated with increased risk of death. The magnitude of association is controversial and potential causes remain unknown. Patients in the registry of the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial form the basis for this report. Baseline variables, in particular the presence or absence of a history of atrial fibrillation/flutter, were examined in relation to survival. Multivariate Cox regression was used to adjust for differences in important baseline co-variables using 27 pre-selected variables. There were 3762 subjects who were followed for an average of 773 +/- 420 days; 1459 (39 %) qualified with ventricular fibrillation and 2303 (61 %) with ventricular tachycardia. A history of atrial fibrillation/flutter was present in 24.4 percent. There were many differences in baseline variables between those with and those without a history of atrial fibrillation/flutter. After adjustment for baseline differences, a history of atrial fibrillation/flutter remained a significant independent predictor of mortality, (relative risk=1.20; 95 % confidence intervals=1.03-1.40; p=0.020). Antiarrhythmic drug use, other than amiodarone or sotalol, was also a significant independent predictor of mortality (relative risk 1.34; 95 % confidence intervals 1.07-1.69, p=0.011. Atrial fibrillation/flutter is a significant independent risk factor for increased mortality in patients presenting with ventricular tachyarrhythmias. This risk may have been overestimated in previous studies that could not adjust for the proarrhythmic effects of antiarrhythmic drugs other than amiodarone or sotalol. C1 Univ Calgary, Div Cardiol, Calgary, AB T2N 1N4, Canada. Maine Med Ctr, Dept Cardiol, Portland, ME 04102 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Case Western Reserve Univ, Div Cardiol, Cleveland, OH 44106 USA. Univ Iowa Hosp & Clin, Div Cardiol, Iowa City, IA 52242 USA. Univ Rochester, Cardiol Unit, Rochester, NY USA. Oregon Hlth Sci Univ, Div Cardiol, Portland, OR 97201 USA. NHLBI, Clin Trials Res Grp, NIH, Bethesda, MD 20892 USA. Wilson Reg Med Ctr, Cardiol Associates, Johnson City, NY USA. RP Wyse, DG (reprint author), Univ Calgary, Div Cardiol, Room G009,3330 Hosp Dr NW, Calgary, AB T2N 1N4, Canada. FU NHLBI NIH HHS [N01-HC-25117] NR 14 TC 46 Z9 48 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1383-875X J9 J INTERV CARD ELECTR JI J. Interv. Card. Electrophysiol. PY 2001 VL 5 IS 3 BP 267 EP 273 DI 10.1023/A:1011460631369 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 462HD UT WOS:000170413900004 PM 11500581 ER PT J AU McGaha, T Saito, S Phelps, RG Gordon, R Noben-Trauth, N Paul, WE Bona, C AF McGaha, T Saito, S Phelps, RG Gordon, R Noben-Trauth, N Paul, WE Bona, C TI Lack of skin fibrosis in tight skin (TSK) mice with targeted mutation in the interleukin-4R alpha and transforming growth factor-beta genes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE emphysema; interleukin-4R; transforming growth factor-beta sclerosis; tight skin ID TGF-BETA; T-CELLS; CONNECTIVE-TISSUE; FIBRILLIN-1 GENE; SCLERODERMA FIBROBLASTS; INFLAMMATORY RESPONSE; SYSTEMIC-SCLEROSIS; COLLAGEN GENE; IFN-GAMMA; MOUSE AB Scleroderma is a disorder characterized by fibrosis of the skin and internal organs and autoimmunity. Whereas the cause is unknown, interleukin-4 and transforming growth factor-beta have been postulated to play a major part in the fibrosis. To investigate the part played by these cytokines, we prepared TSK/+ mice with a targeted mutation in the interleukin-4R alpha or transforming growth factor-beta genes. The breeding failed to produce TSK/+ transforming growth factor-beta-/- mice so analysis of the role of transforming growth factor-beta was limited to TSK/+ transforming growth factor-beta+/- mice. We observed that TSK/+ interleukin-4R alpha-/- did not develop dermal thickening, and deletion of one allele of the transforming growth factor-beta gene resulted in diminished dermal thickness compared with TSK/+ mice; however, the deletion of interleukin-4R alpha or transforming growth factor-beta had no effect on lung emphysema, which is another characteristic of TSK syndrome. Electron microscopic analysis of skin showed that the collagen fibrils in TSK/+ interleukin-4R alpha-/- mice exhibit normal periodicity but have a smaller diameter than the fibers found in C57BL/6 mice. Analysis of skin and serum samples showed that the deletion of interleukin-4R alpha or one allele of transforming growth factor-beta prevented the increase of skin thickness paralleled with a decrease in the dermal hydroxyproline content and development of autoantibodies associated with TSK syndrome. These results demonstrate the importance of interleukin-4 and transforming growth factor-beta for the development of cutaneous fibrosis in vivo and suggest an important part for these cytokines in wound healing and connective tissue maintenance in general. C1 Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA. NIAID, Immunol Lab, Bethesda, MD 20892 USA. RP Bona, C (reprint author), Mt Sinai Sch Med, Dept Microbiol, Box 1124,1 Gustave L Levy Pl, New York, NY 10029 USA. EM bonac01@doc.msm.edu OI McGaha, Tracy/0000-0003-4721-9301 FU NIAID NIH HHS [P01AI24671-12] NR 40 TC 83 Z9 83 U1 1 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2001 VL 116 IS 1 BP 136 EP 143 DI 10.1046/j.1523-1747.2001.00217.x PG 8 WC Dermatology SC Dermatology GA 399DZ UT WOS:000166797200018 PM 11168809 ER PT J AU Zhou, J Anderson, K Bievre, M Ng, S Bondy, CA AF Zhou, J Anderson, K Bievre, M Ng, S Bondy, CA TI Primate mammary gland insulin-like growth factor system: Cellular localization and regulation by sex steroids SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE breast cancer; estrogen; progesterone; proliferation; apoptosis; IGF receptor; IGFBP3 ID HUMAN-BREAST-CANCER; II MESSENGER-RNA; GENE-EXPRESSION; FACTOR RECEPTOR; PROTEIN EXPRESSION; BINDING-PROTEINS; TRANSGENIC MICE; TISSUE; PROLIFERATION; ESTROGEN AB Background: Insulin-like growth factor 1 (IGF1) plays a critical role in estrogen-induced uterine proliferation, but it is unclear whether this estromedin function occurs in other estrogen-sensitive tissues such as the mammary gland, To elucidate this possibility, we investigated the cellular localization and hormonal regulation of mRNAs for IGF1 and 2, their cognate receptors (IGF1R, IGF2R), and IGF binding proteins 2-5 (BPs 2-5) in the rhesus monkey mammary gland. Methods: Ovariectomized monkeys were treated with placebo, estradiol (E2), and E2 plus progesterone (E2/P4) for 3 days, after which mammary tissue was harvested for in situ hybridization and immunohistochemical analyses. Results: IGF1 and IGF2 mRNA levels were significantly increased and BP2 mRNA decreased by E2 and by E2/P4 treatment, IGF1R mRNA was increased by combined E2/P treatment but not by E2 alone. BP5 mRNA was decreased by E2/P4, No differences in IGF2R, BP3, and BP4 mRNA levels were detected in any treatment group, Mammary IGF1 and IGF2 mRNA levels were both positively correlated with local epithelial proliferation, assessed by immunodetection of the proliferation-specific antigen, Ki67, IGF1 and IGF1R expression were negatively correlated with local programmed cell death, as assessed by the in situ TUNEL method, In contrast, BP2 expression was negatively correlated with epithelial proliferation and positively correlated with programmed cell death, IGF2R, BP3, BP4, and BP5 levels were not significantly correlated with either proliferation or death. Conclusions: Thus, E2-induced proliferation is associated with upregulation of both IGF1 and IGF2 expression and downregulation of BP2 expression, These data suggest that the local mammary IGF system is involved in sex steroid-induced mammary epithelial cell hyperplasia. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), BG 10,Rm 10N262,10 Ctr Dr 1862, Bethesda, MD 20892 USA. NR 31 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2001 VL 49 IS 1 BP 47 EP 55 DI 10.2310/6650.2001.34090 PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 396RD UT WOS:000166649600009 PM 11217147 ER PT J AU Brown, P Cervenakova, L Diringer, H AF Brown, P Cervenakova, L Diringer, H TI Blood infectivity and the prospects for a diagnostic screening test in Creutzfeldt-Jakob disease SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Review ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; FLUORESCENT-LABELED PEPTIDES; CAPILLARY-ELECTROPHORESIS; PRION PROTEIN; VARIANT CJD; IMMUNO-PCR; COMPONENTS; TRANSFUSION; AGENT; PRPSC C1 NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. Amer Red Cross, Jerome H Holland Lab, Rockville, MD USA. Robert Koch Inst, D-1000 Berlin, Germany. RP Brown, P (reprint author), NINDS, Cent Nervous Syst Studies Lab, NIH, Bldg 36,Room 4A-05,36 Convent Dr,MSC 4122, Bethesda, MD 20892 USA. NR 37 TC 101 Z9 108 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD JAN PY 2001 VL 137 IS 1 BP 5 EP 13 DI 10.1067/mlc.2001.111951 PG 9 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 392KP UT WOS:000166410500001 PM 11150018 ER PT J AU Hammerschmidt, DE Brown, P AF Hammerschmidt, DE Brown, P TI The transmissibility of Creutzfeldt-Jakob disease SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Hammerschmidt, DE (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD JAN PY 2001 VL 137 IS 1 BP 77 EP 78 PG 2 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 392KP UT WOS:000166410500010 ER PT J AU Farrar, WL Hodge, D AF Farrar, WL Hodge, D TI IL-6 regulation of the human methytransferase (HDNMT) gene in human erythroleukemia cells. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, Cytokine Mol Mechanism Sect, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NCI, SAIC, Intramural Res Support Program, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 19 BP 23 EP 23 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200020 ER PT J AU Shakhov, AN Nedospasov, SA AF Shakhov, AN Nedospasov, SA TI Expression profiling in lymphotoxin and tumor necrosis factor knockout mice SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, IRSP, SAIC Frederick, Frederick, MD 21702 USA. VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 21 BP 23 EP 23 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200022 ER PT J AU Huang, J Murray, R Durum, S Muegge, K AF Huang, J Murray, R Durum, S Muegge, K TI IL-7 controls chromatin accessibility for the TCR gamma V(D)J recombination via histone acetylation SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD USA. DNAX Res Inst Mol & Cellular Biol Inc, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 23 BP 24 EP 24 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200024 ER PT J AU Murray, PJ Rutschman, R Baldovich, K Hesse, M Wynn, T Lang, R AF Murray, PJ Rutschman, R Baldovich, K Hesse, M Wynn, T Lang, R TI Regulation of macrophage arginase I expression SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA. NIH, NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 28 BP 25 EP 25 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200029 ER PT J AU Durum, SK Muegge, K Khaled, AR AF Durum, SK Muegge, K Khaled, AR TI Bax deletion restores thymocyte development in IL-7R alpha -/- mice. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, IRSP,SAIC, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 34 BP 26 EP 26 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200035 ER PT J AU Ruscetti, FW Young, HA Petrow-Sadowski, C Bagni, R Mikovits, JA AF Ruscetti, FW Young, HA Petrow-Sadowski, C Bagni, R Mikovits, JA TI Combined cytokine stimulation of human naive CD4+T cells results in IFN-gamma production in absence of hypomethylation of the IFN-gamma gene promoter SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, CCR, BRL, LBS, Frederick, MD 21702 USA. NCI, CCR, LEI, Frederick, MD 21702 USA. NCI, SAIC, BCDP, Frederick, MD 21702 USA. NCI, Frederick, MD 21702 USA. NCI, SAIC, STB, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 41 BP 28 EP 28 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200042 ER PT J AU Yang, D Chen, Q Chertov, O Anderson, M Hirata, M Oppenheim, JJ AF Yang, D Chen, Q Chertov, O Anderson, M Hirata, M Oppenheim, JJ TI Identification of the receptor that human LL-37 utilizes to activate human neutrophils, monocytes, and T cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NIH, Natl Canc Inst, Mol Immunoregulat Lab, Frederick, MD USA. Magainin Res Inst, Plymouth Meeting, PA USA. Iwate Med Univ, Morioka, Iwate 020, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 42 BP 28 EP 28 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200043 ER PT J AU Howard, OMZ Gertz, B Wooters, J Lockett, S Oppenheim, JJ AF Howard, OMZ Gertz, B Wooters, J Lockett, S Oppenheim, JJ TI Detection of a novel component of CCR5 ligand induced trafficking SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, CCR, LMI, Frederick, MD 21701 USA. NCI, SAIC, Frederick, MD 21701 USA. Genet Inst Inc, Cambridge, MA 02140 USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 51 BP 30 EP 30 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200052 ER PT J AU Sporri, B Kovanen, PE Sasaki, A Yoshimura, A Leonard, WJ AF Sporri, B Kovanen, PE Sasaki, A Yoshimura, A Leonard, WJ TI JAB/SOCS1/SSI-1 is an IL-2-induced inhibitor of IL-2 signaling SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 70 BP 35 EP 35 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200071 ER PT J AU Kruth, HS Huang, W Zhang, WY Ishii, I AF Kruth, HS Huang, W Zhang, WY Ishii, I TI PMA inhibits plasmin-mediated release of aggregated LDL from macrophages. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NIH, NHLBI, Sect Expt Atherosclerosis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 95 BP 40 EP 40 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200095 ER PT J AU McCartney-Francis, NL Wahl, SM AF McCartney-Francis, NL Wahl, SM TI Unregulated signaling pathways in TGF-beta 1 deficient mice SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 103 BP 42 EP 42 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200103 ER PT J AU Drutskaya, M Kuprash, D Nedospasov, S Keller, J AF Drutskaya, M Kuprash, D Nedospasov, S Keller, J TI Dual function of TNF as regulator of myelopoiesis in long-term bone marrow cultures. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. SAIC Frederick, IRSP, Frederick, MD USA. NCI, DBS, LMI, Frederick, MD 21701 USA. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 125 BP 47 EP 48 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200125 ER PT J AU Tumanov, AV Kuprash, DV Lagarkova, MA Abe, K Shakhov, AN Stewart, C Chervonsky, AV Nedospasov, SA AF Tumanov, AV Kuprash, DV Lagarkova, MA Abe, K Shakhov, AN Stewart, C Chervonsky, AV Nedospasov, SA TI Lymphotoxin (LT) function in vivo as dissected by inactivation of LT complex in B cells. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. LMI, Frederick, MD USA. CDBL, Frederick, MD USA. IRSP, Frederick, MD USA. SAIC Frederick, Frederick, MD USA. NCI, Frederick, MD 21701 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 124 BP 47 EP 47 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200124 ER PT J AU Nedospasov, SA AF Nedospasov, SA TI Biological functions of Tumor Necrosis Factor and Lymphotoxin in vivo assessed using a novel panel of knockout mice. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, SAIC Frederick, IRSP, Frederick, MD USA. VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 126 BP 48 EP 48 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200126 ER PT J AU Sahagun-Ruiz, A Colla, JS Juhn, J Gao, JL Murphy, PM McDermott, DH AF Sahagun-Ruiz, A Colla, JS Juhn, J Gao, JL Murphy, PM McDermott, DH TI Contrasting evolution of the human leukocyte N-formylpeptide receptor subtypes FPR and FPRL1R SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NIH, NIAID, Host Def Lab, Mol Signaling Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 130 BP 49 EP 49 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200130 ER PT J AU Zhou, M Zhang, YH Ardans, JA Wahl, LM AF Zhou, M Zhang, YH Ardans, JA Wahl, LM TI Regulation of TNF alpha and caspases by IFN gamma results in differential MMP-1 and MMP-9 production by GM-CSF and TNF alpha treated monocytes SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NIH, NIDCR, Immunopathol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 165 BP 56 EP 56 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200165 ER PT J AU Abdi, R Huong, TTB Sahagun-Ruiz, A Murphy, PM Brenner, BM Milford, EL McDermott, DH AF Abdi, R Huong, TTB Sahagun-Ruiz, A Murphy, PM Brenner, BM Milford, EL McDermott, DH TI Chemokine receptor polymorphism and risk of acute rejection in human renal transplantation SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. NIH, NIAID, Host Def Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 183 BP 60 EP 60 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200183 ER PT J AU Murphy, PM AF Murphy, PM TI Genetic analysis of chemokine roles in human disease SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 181 BP 60 EP 60 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200181 ER PT J AU Kuhns, DB Gallin, JI AF Kuhns, DB Gallin, JI TI Induction of neutrophil IL-8 by fibrinogen and fMLF or LTB4 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 SIAC Frederick, Frederick, MD 21702 USA. NIH, NIAID, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 189 BP 61 EP 62 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200189 ER PT J AU Vazquez, N Wild, T Wahl, SM AF Vazquez, N Wild, T Wahl, SM TI Signaling pathways and gene expression in HIV-1 infected macrophages SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NIH, NIDCR, OIIB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 203 BP 64 EP 65 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200203 ER PT J AU Bertholet, S Dickensheets, HL Donnelly, RP Sacks, D Kenney, RT AF Bertholet, S Dickensheets, HL Donnelly, RP Sacks, D Kenney, RT TI An impaired interferon gamma signaling pathway in Leishmania-infected human macrophages is associated with the induction of Suppressor Of Cytokine Signaling-3 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 US FDA, CBER, OVRR, Rockville, MD 20857 USA. US FDA, CBER, OTRR, Rockville, MD 20857 USA. NIH, NIAID, LPD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 214 BP 67 EP 67 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200214 ER PT J AU Mendez, S Belkaid, Y Flowers, E Sacks, DL AF Mendez, S Belkaid, Y Flowers, E Sacks, DL TI Leishmania species differentially modulates macrophage migration and expression of cell adhesion molecules SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NIH, NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 215 BP 67 EP 67 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200215 ER PT J AU Greenwell-Wild, T Vazquez, N Sim, D Wahl, SM AF Greenwell-Wild, T Vazquez, N Sim, D Wahl, SM TI Mycobacterium avium regulation of macrophage cytokine production SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NIH, NIDCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 217 BP 68 EP 68 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200217 ER PT J AU Rossio, JL Whitby, D Hallett, K Ryan, R Arthur, LO Lifson, JD AF Rossio, JL Whitby, D Hallett, K Ryan, R Arthur, LO Lifson, JD TI Multiplexed cytokine assay of serum from HIV-infected patients with differing disease presentations SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, AIDS Vaccine Program, Frederick, MD 21702 USA. SAIC, Frederick, MD 21702 USA. Linco Res Inc, St Charles, MO 63304 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 228 BP 70 EP 70 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200228 ER PT J AU Turpin, JA Dong, HF Howard, OMZ Halverson, D Carrington, M Dean, M Osterling, C Oppenheim, JJ AF Turpin, JA Dong, HF Howard, OMZ Halverson, D Carrington, M Dean, M Osterling, C Oppenheim, JJ TI CCR5 variants permissive for HIV-1 infection show distinct functional responses to CCL3, CCL4 and CCL5 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 SAIC Frederick, IRSP, Frederick, MD USA. NCI, LMI, CCR, Frederick, MD 21701 USA. NCI, LGD, CCR, Frederick, MD 21701 USA. So Res Inst, Frederick, MD USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 227 BP 70 EP 70 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200227 ER PT J AU Anderson, SK Nalewaik, R Makrigiannis, A Saleh, A AF Anderson, SK Nalewaik, R Makrigiannis, A Saleh, A TI Characterization of a novel Ly49 promoter that is active in immature cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, SAIC, Canc Res Ctr, Expt Immunol Lab, Frederick, MD 21702 USA. NCI, SAIC, Intramural Res Support Program, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 238 BP 72 EP 72 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200238 ER PT J AU Ghosh, P Buchholz, MA Yano, S Longo, DL AF Ghosh, P Buchholz, MA Yano, S Longo, DL TI Effect of rapamycin on the cyclosporin A-resistant CD28-mediated costimulatory pathway SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, Immunol Lab, Lymphocyte Cell Biol Sect,NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 253 BP 76 EP 76 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200253 ER PT J AU Bream, JH Cheng, RY Curiel, R Grusby, M Aune, T Young, HA AF Bream, JH Cheng, RY Curiel, R Grusby, M Aune, T Young, HA TI Synergistic effect of IL-4 on IL-2-and IL-12-induction of murine IFN-gamma expression in NK cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, CCR, Expt Immunol Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 265 BP 79 EP 79 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200265 ER PT J AU Caler, E Noben-Trauth, N Sacks, D Belkaid, Y AF Caler, E Noben-Trauth, N Sacks, D Belkaid, Y TI IFN gamma depletion enhances inflammation and lesion progression of Leishmania major infected IL-4 deficient C57BL/6 mice. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NIH, NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 274 BP 81 EP 81 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200274 ER PT J AU Culp, WD Perez-Diez, A Massey, RD Matzinger, P AF Culp, WD Perez-Diez, A Massey, RD Matzinger, P TI The kinetics of an IFN gamma response SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 305 BP 88 EP 88 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200305 ER PT J AU Azimi, N Nagai, M Mariner, J Jacobson, S Waldmann, TA AF Azimi, N Nagai, M Mariner, J Jacobson, S Waldmann, TA TI IL-15 plays an important role in the pathogenesis of HAM/TSP through activation of the T cells and persistence of antigen specific CD8 cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, Metab Branch, Bethesda, MD 20892 USA. NINCDS, Viral Immunol Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 332 BP 95 EP 95 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200331 ER PT J AU Wang, JM Yazawa, H Yu, ZX Takea, K Le, YY Gong, WH Ferrans, VJ Li, CC Oppenheim, JJ AF Wang, JM Yazawa, H Yu, ZX Takea, K Le, YY Gong, WH Ferrans, VJ Li, CC Oppenheim, JJ TI The role of the G-protein coupled receptor FPRL1 in Alzheimer's disease: Its relevance to cellular up-take of beta amyloid peptide and fibrilar formation by macrophages SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. SAIC Frederick, IRSP, Frederick, MD 21702 USA. NIH, NHLBI, Pathol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 349 BP 99 EP 99 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200348 ER PT J AU Waldmann, T Azimi, N Dubois, S Tagaya, Y AF Waldmann, T Azimi, N Dubois, S Tagaya, Y TI Contrasting roles of IL-2 and IL-15 in the life and death of lymphocytes: implications for immunotherapy SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, Metab Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 355 BP 100 EP 100 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200354 ER PT J AU Wiltrout, RH Gruys, E Subleski, J Nagashima, K Back, TC Wigginton, JM AF Wiltrout, RH Gruys, E Subleski, J Nagashima, K Back, TC Wigginton, JM TI Co-dependency of tumor regression and anti-angiogenesis on both IFN-gamma and Fas/FasL in mice treated with IL-12/pulse IL-2 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, CCR, Expt Immunol Lab, Bethesda, MD 20892 USA. SAIC Frederick, IRSP, Frederick, MD USA. NCI, DCS, Pediat Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 353 BP 100 EP 100 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200352 ER PT J AU Chen, WJ Frank, M Jin, WW Lei, KJ Hardegen, N Wahl, SM AF Chen, WJ Frank, M Jin, WW Lei, KJ Hardegen, N Wahl, SM TI Transforming growth factor-beta 1 induces anergic/suppressor CD4+CD25+CTLA-4+T cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NIH, NIDCR, OIIB, Cellular Immunol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2001 SU S MA 362 BP 102 EP 102 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 480UY UT WOS:000171482200361 ER PT J AU Weber, HA Zart, MK Ferguson, SL Greaves, JG Clark, AP Harris, RK Overstreet, D Smith, C AF Weber, HA Zart, MK Ferguson, SL Greaves, JG Clark, AP Harris, RK Overstreet, D Smith, C TI Separation and quantitation of isoquinoline alkaloids occurring in goldenseal SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID BERBERINE; PALMATINE AB An isocratic high-performance liquid chromatography (HPLC) method was developed for the analysis of hydrastinine, palmatine, berberine, hydrastine, and canadine, all alkaloid components known to be present in goldenseal root powder. Optimized separation was achieved on a Zorbax Eclipse-XDB column at 30 degreesC using a mobile phase of 10 mM ammonium acetate/acetonitrile (70:30, v/v) at a flow rate of 1.0 mL/min with ultraviolet detection at 235 nm. The method showed linearity for palmatine, berberine, hydrastine, and canadine at approximately 4-400 mug/mL, while hydrastinine was linear at approximately 4-80 mug/mL. Method precision and robustness were investigated. An example of an HPLC analysis of goldenseal root powder extract is presented here also. These studies indicate that the method described here is usable for analysis of goldenseal extracts. C1 Midwest Res Inst, Kansas City, MO 64110 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Weber, HA (reprint author), Midwest Res Inst, Kansas City, MO 64110 USA. NR 11 TC 13 Z9 14 U1 2 U2 6 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2001 VL 24 IS 1 BP 87 EP 95 DI 10.1081/JLC-100000329 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 414PP UT WOS:000167675500008 ER PT J AU Xu, HY Issaq, SH McCloud, TG Issaq, HJ AF Xu, HY Issaq, SH McCloud, TG Issaq, HJ TI The separation of a penicillium fungal extract by thin layer chromatography and HPLC: A comparative study SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID TAXUS-BREVIFOLIA; TAXOL AB The separation of a Penicillium fungal extract by two dimensional-multimodal thin layer chromatography and gradient high performance liquid chromatography is reported. The fungal extract was resolved on a cyano derivatized silica gel TLC plate using two dimensional development; first dimension in methylene chloride: hexane:acetic acid (9:10:1), taken out, dried, turned 90 degrees, and developed in the second dimension in acetonitrile:methanol: water (40:37:32). Over 20 different spots were observed under UV radiation. Three different mobile phase gradients, acetonitrile, methanol, and tetrahydrofuran as primary organic solvents were used. Different selectivities; resulted in each gradient. The best result was obtained using the acetonitrile gradient, 25% to 100% acetonitrile in 30 minutes. Also, it was found that using photo diode array detection in natural products research is a must when quantitation is required, since the mixture contains compounds of different absorptivities. The results show that changing the wave length of detection resulted in different peak heights (areas). C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, POB B, Frederick, MD 21702 USA. NR 9 TC 1 Z9 1 U1 1 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2001 VL 24 IS 5 BP 625 EP 633 DI 10.1081/JLC-100103399 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 439JL UT WOS:000169113300002 ER PT J AU Sookkumnerd, T Hsu, PP Hsu, JT Ito, Y AF Sookkumnerd, T Hsu, PP Hsu, JT Ito, Y TI Shear stress and precipitation effect on enzymatic activity of alpha-chymotrypsin in centrifugal precipitation chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID AMMONIUM-SULFATE; PROTEINS; FRACTIONATION; PRINCIPLE AB The result of a systematic investigation into the effect of shear stress and precipitation in the separation channel of centrifugal precipitation chromatography on the enzymatic activity of alpha -chymotrypsin at room temperature is reported. From the experiment, it was observed that more than 90% of alpha -chymotrypsin remains active after being subjected only to the shear stress in the separation channel, with the exception of alpha -chymotrypsin subjected to a relatively high water flow rate. Upon introducing the ammonium sulfate gradient in the separation channel, it was observed that 89.03% of the enzyme remained active after being subjected to both shear stress and precipitation in centrifugal precipitation chromatography. As a result, it can be concluded that centrifugal precipitation chromatography should be friendly to most proteins under the appropriate operating conditions. C1 Lehigh Univ, Dept Chem Engn, Biopharmaceut Technol Inst, Bethlehem, PA 18015 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Lehigh Univ, Dept Chem Engn, Biopharmaceut Technol Inst, Bethlehem, PA 18015 USA. EM jth0@lehigh.edu NR 18 TC 2 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1082-6076 EI 1520-572X J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2001 VL 24 IS 7 BP 947 EP 955 DI 10.1081/JLC-100103421 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 439JN UT WOS:000169113500004 ER PT J AU Yang, FQ Zhang, TY Xu, GQ Chou, FE Ito, Y AF Yang, FQ Zhang, TY Xu, GQ Chou, FE Ito, Y TI pH-modulated stepwise elution CCC and its application to the preparative separation of hydroxyanthraquinone compounds from traditional Chinese medicinal herbs SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article; Proceedings Paper CT 1st International Conference on Countercurrent Chromatography (CCC 2000) CY SEP 11-14, 2000 CL LONDON, ENGLAND ID SPEED COUNTERCURRENT CHROMATOGRAPHY; FLAVONOIDS AB Analytical and preparative high-speed countercurrent chromatography was successfully used for the separation of hydroxyanthraquinones from traditional Chinese medicine such as Rheum officinale Baill (Dahuang) and Polygonum cuspidatum Sieb. Et Zucc (Huzhang) using pH-modulated stepwise elution. Four major components including chrysophanol, emodin, physcion, and aloe-emodin were isolated each at over 98% purity. C1 Beijing Inst New Technol Applicat, Beijing Res Ctr Separat & Purificat Technol Nat P, Beijing 100035, Peoples R China. Pharmatech Res Corp, Baltimore, MD 21212 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Yang, FQ (reprint author), Beijing Inst New Technol Applicat, Beijing Res Ctr Separat & Purificat Technol Nat P, Beijing 100035, Peoples R China. NR 8 TC 10 Z9 11 U1 1 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2001 VL 24 IS 11-12 BP 1617 EP 1628 DI 10.1081/JLC-100104367 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 456VP UT WOS:000170103200007 ER PT J AU Cao, XL Tian, Y Zhang, TY Ito, Y AF Cao, XL Tian, Y Zhang, TY Ito, Y TI Separation-and purification of three individual catechins from tea polyphenol mixture by CCC SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article; Proceedings Paper CT 1st International Conference on Countercurrent Chromatography (CCC 2000) CY SEP 11-14, 2000 CL LONDON, ENGLAND ID GREEN AB Countercurrent chromatography (CCC) was applied to the separation and purification of three catechins, i.e., epigallocatechin-3-o-gallate (EGCG), gallocatechin-3-o-gallate (GCG), and epicatechin-3-o-gallate (ECG) from a polyphenol mixture. Analytical CCC was used to select suitable two-phase solvent systems from ethyl acetate-ethanol-water and hexane-ethyl acetate-water Systems by adjusting mutual volume ratios in each system. Using the optimized solvent systems, the preparative separation was successfully performed by two-step separation where 1 g crude sample was efficiently purified, yielding 275 mg of EGCG, 140 mg of GCG, and 130 ing of ECG, each at high purity about 98% by HPLC analysis. The structures of these catechins were identified by FAB-MS, 1 H, and C-13 NMR. C1 Beijing Inst New Technol Applicat, Beijing 100035, Peoples R China. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Cao, XL (reprint author), Beijing Inst New Technol Applicat, Beijing 100035, Peoples R China. NR 9 TC 10 Z9 15 U1 1 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2001 VL 24 IS 11-12 BP 1723 EP 1732 DI 10.1081/JLC-100104374 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 456VP UT WOS:000170103200014 ER PT J AU Shibusawa, Y Hosojima, T Nakata, M Shindo, H Ito, Y AF Shibusawa, Y Hosojima, T Nakata, M Shindo, H Ito, Y TI One-step purification of cholinesterase from human serum by CCC SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article; Proceedings Paper CT 1st International Conference on Countercurrent Chromatography (CCC 2000) CY SEP 11-14, 2000 CL LONDON, ENGLAND ID COIL PLANET CENTRIFUGE; PREPARATIVE COUNTERCURRENT CHROMATOGRAPHY; POLYMER PHASE SYSTEMS; PROTEIN SEPARATION; STATIONARY-PHASE; ROTARY SEALS; APPARATUS; SPEED; DESIGN; ACCELERATION AB The type XL cross-axis coil planet centrifuge (CPC) was successfully utilized for purification of cholinesterase (ChE) from human serum by countercurrent chromatography (CCC). Aqueous-aqueous polymer phase systems composed of polyethylene glycol-potassium phosphate buffers were tested at various pHs, ranging from 6.8 to 9.2 for the distribution ratios (D) of ChE, human serum albumin, alpha- and gamma -globulins. The CCC separation was performed with optimized polymer phase systems in two different coiled columns. The best purification was achieved with 16.0% PEG 600-12.5% potassium phosphate at pH 9.2, by eluting the lower phase at 0.5 mL/min through the small capacity column in which ChE was purified directly from human serum within 2h. The ChE fractions confirmed by the enzymatic activity were free of serum proteins by SDS PAGE analysis. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Tokyo Univ Pharm & Life Sci, Tokyo 1920392, Japan. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NR 21 TC 8 Z9 9 U1 1 U2 6 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2001 VL 24 IS 11-12 BP 1733 EP 1744 DI 10.1081/JLC-100104375 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 456VP UT WOS:000170103200015 ER PT J AU Shibusawa, Y Iino, S Shindo, H Ito, Y AF Shibusawa, Y Iino, S Shindo, H Ito, Y TI Separation of chicken egg white proteins by high-speed countercurrent chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID COIL PLANET CENTRIFUGE; PURIFICATION; PHASE; LIPOPROTEINS; SYSTEMS AB Chicken egg white proteins were fractionated by high-speed counter-current chromatography (HSCCC) using a cross-axis coil planet centrifuge (X-axis CPC). The separation was performed with an aqueous polymer two-phase system composed of 16% polyethylene glycol (PEG) 1000 and 12.5% potassium phosphate buffer at different pH of 6.8, 8.0, and 9.2. From 20 g of the crude egg white solution, the best separation was achieved with a polymer phase system at pH 8.0 by eluting the lower phase at 1.0 mL/min. After the sequential elution of ovotransferrin, ovalbumin, and lysozyme from the column, ovomucin still retained in the column was eluted in the reverse direction with upper PEG-rich phase. All four proteins in the CCC fractions were identified by SDS gel electrophoresis with Coomassie brilliant blue staining. C1 Tokyo Univ Pharm & Life Sci, Dept Analyt Chem, Sch Pharm, Tokyo 1920392, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shibusawa, Y (reprint author), Tokyo Univ Pharm & Life Sci, Dept Analyt Chem, Sch Pharm, 1432-1 Horinouchi, Tokyo 1920392, Japan. NR 17 TC 13 Z9 17 U1 3 U2 12 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2001 VL 24 IS 13 BP 2007 EP 2016 DI 10.1081/JLC-100104442 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 456VQ UT WOS:000170103300012 ER PT J AU Qu, Y Vandesande, F Arckens, L AF Qu, Y Vandesande, F Arckens, L TI Identification and quantification of monoaminergic neuromodulators in the sub-cortical region of cat visual cortex by microbore HPLC-ED and protein assay SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ELECTROCHEMICAL DETECTION; METABOLITES; NEUROTRANSMITTERS; CATECHOLAMINES; MODULATION; SEROTONIN; INJECTION; DOPAMINE AB Removal of retinal input from a restricted region of adult visual cortex leads to a substantial reorganisation of the retinotopy within the deprived zone. To investigate the role of the total (intra- and extracellular) concentration of the monoaminergic neuromodulators in the sub-cortical region of cat visual cortex, which is possibly involved in this reorganisation mechanism, a method for identification and quantification of noradrenaline, dopamine, serotonin, and their major metabolites, 3,4-dihydroxyphenylacetic acid, 4-hydroxy-3-methoxyphenylacetic acid, 5-hydroxyindole-3-acetic acid in small amounts of brain extracts has been developed and validated. Control or retinal lesion cats were killed with pentobarbital; the brains were quickly frozen, and 200 mum cryostat sections were cut. Under visual control through a surgical microscope, the cortical tissue was first separated from the underlying white matter Three pieces of tissue measuring 2 x 4 mm(2), containing the six cortical layers, were sampled out from the different cortical regions subserving different parts of the visual field (central and peripheral portion of area 17). After homogenising these samples in 80 muL, 0.01M HCl which included 0.01% cysteine as antioxidant, 10 muL of the supernatant was injected directly onto the microbore HPLC system, separated on a microbore column (150 x 1 mm i.d.; ODS), and the components detected electrochemically at a potential of +0.75V. The flow rate of mobile phase through the column was 44 muL/min. The specificity; recovery, analytical precision, calibration curves, and detection limits for each neurotransmitter were determined. In order to express the total neuromodulator concentration as pg/mug protein, the pellets obtained after centrifugation were used for protein determination. A modified protein assay with non-linear regression equation data processing is also described. C1 Katholieke Univ Leuven, Inst Zool, Lab Neuroendocrinol & Immunol Biotechnol, B-3000 Louvain, Belgium. RP Qu, Y (reprint author), NIA, Sect Brain Physiol & Metab, NIH, Bldg 10,Rm 6N202, Bethesda, MD 20892 USA. RI Arckens, Lutgarde/C-3822-2016 NR 17 TC 0 Z9 0 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2001 VL 24 IS 14 BP 2087 EP 2100 DI 10.1081/JLC-100104893 PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 462MX UT WOS:000170424800003 ER PT J AU Lei, L Yang, FQ Zhang, TY Tu, PF Wu, LJ Chen, FK Ito, Y AF Lei, L Yang, FQ Zhang, TY Tu, PF Wu, LJ Chen, FK Ito, Y TI Preparative isolation and purification of phenylethanoid glycosides from the extract of faeces of beagle dogs by high-speed countercurrent chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article AB High-speed countercurrent chromatography (HSCCC) was applied to the separation of acteoside and isoacteoside from a crude extract from canine faeces after the dogs were orally administered phenylethanoid glycosides (PhGs). Two-step separation with a quaternary two-phase solvent system composed of ethyl acetate-n-butanol-ethanol-water (system 1, 35:6:6:50, v/v; system 2, 30:10:6:50, v/v) was used. HPLC analysis of final CCC fractions revealed that the two main PhGs showed purity of over 95%. Their chemical structures were identified by (HNMR)-H-1, (CNMR)-C-13, FAB-MS. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Beijing Inst New Technol Applicat, Beijing 100035, Peoples R China. Shenyang Phamraceut Univ, Shenyang 110015, Peoples R China. Peiking Univ, Sch Pharmaceut Sci, Dept Nat Med, Beijing 100083, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 4 Z9 4 U1 1 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2001 VL 24 IS 14 BP 2187 EP 2195 DI 10.1081/JLC-100104901 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 462MX UT WOS:000170424800011 ER PT J AU Du, QZ Jiang, HY Ito, Y AF Du, QZ Jiang, HY Ito, Y TI Separation of theaflavins of black tea. High-speed countercurrent chromatography vs. sephadex LH-20 gel column chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article AB Performance of two chromatographic techniques, high-speed countercurrent chromatography (HSCCC) and conventional Sephadex LH-20 gel column chromatography (GLC), was compared in the separation of theaflavins from the extract of black tea leaves. The HSCCC run was carried out with a two-phase solvent system composed of hexane/ethyl acetate/methanol/water (1:3:1:6, v/v) by eluting the lower aqueous phase at 2 mL/min at 800 rpm where 200 mg of the sample was resolved into three peaks corresponding to theaflavin, theaflavin-3,3'-gallate, and a mixture of theaflavin-3-gallate and theaflavin-3'-gallate in 4.1 hrs. Although, Sephadex column chromatography yielded a similar separation for 100 mg of the same sample, it required a much longer elution time of 21 hrs. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Hangzhou Univ Commerce, Inst Food & Biol Engn, Hangzhou 310035, Peoples R China. Chinese Acad Agr Sci, Grad Sch, Beijing 100081, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10,Rm 7N322, Bethesda, MD 20892 USA. NR 7 TC 12 Z9 15 U1 1 U2 5 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2001 VL 24 IS 15 BP 2363 EP 2369 DI 10.1081/JLC-100105147 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 471AL UT WOS:000170904600012 ER PT J AU Issaq, HJ Xu, HY Chan, KC AF Issaq, HJ Xu, HY Chan, KC TI A study of parameters that influence the HPLC and CE separation of double stranded DNA fragments and DNA mutants SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID CONFORMATION POLYMORPHISM ANALYSIS; SINGLE BASE SUBSTITUTIONS; POLYMERASE CHAIN-REACTION; CAPILLARY-ELECTROPHORESIS; POINT MUTATIONS; LIQUID-CHROMATOGRAPHY; TEMPERATURE; MISMATCHES AB The present study evaluates HPLC and CE experimental parameters, such as column packing properties, mobile phase pH, column temperature, and gel type on the separation of DNA fragments and heteroduplexes. The results of this study show that both HPLC and CE are useful techniques for the separation of DNA fragments and for the detection of DNA mutants. Not all HPLC columns tested resolved the DNA fragments or detected the mutation. The packing material type and physical and chemical properties play a significant role. It was found that ion-pair DHPLC is easier and faster than single capillary CE for detecting DNA mutants at their melting temperature (5 min. vs 25 min.). However, CE is faster for the separation of DNA fragments (6.5 min. vs 20 min.). Most HPLC column packing materials tested resolved small DNA fragments, less than 200 bp, but not large fragments, greater than 200 bp. DNA fragments, 21-587 bp, are resolved by DHPLC at 40-50 degreesC, but not at room temperature, using special columns; ultra pure, large pore, high coverage C-18-silica, nonporous C-14-silica or nonporous polystyrene/divinylbenzene and ion-pair gradient elution. CE can resolve the 21-587 bp fragments at room temperature, and at 30 to 50 degreesC. It was also found that fluorocarbon coated capillary filled with polyacryl amide or hydroxycellulose liquid polymers, was more stable than DB-17, however, both capillaries gave good and reproducible CE results. C1 NCI, SAIC Frederick, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI, SAIC Frederick, POB B, Frederick, MD 21702 USA. NR 22 TC 2 Z9 2 U1 1 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2001 VL 24 IS 16 BP 2381 EP 2398 DI 10.1081/JLC-100105946 PG 18 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 478WY UT WOS:000171372100001 ER PT J AU Shinomiya, K Yoshida, K Kabasawa, Y Ito, Y AF Shinomiya, K Yoshida, K Kabasawa, Y Ito, Y TI Countercurrent chromatographic separation of water-soluble vitamins by cross-axis coil planet centrifuge using an ion-pair reagent with polar two-phase solvent system SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID ROTARY SEALS; ASSEMBLIES; EFFICIENCY; APPARATUS AB Countercurrent chromatographic separation of water-soluble vitamins, such as riboflavin sodium phosphate, cyanocobalamin, riboflavin, pyridoxine hydrochloride, and thiamine nitrate was performed using the cross-axis coil planet centrifuge equipped with a pair of eccentric coil assemblies at off-center position. The solvent system used in the present studies was prepared by adding 1.5% of 1-octanesulfonic acid sodium salt, as an ion-pair reagent, to the polar two-phase solvent system composed of 1-butanol and aqueous 0.15 M monobasic potassium phosphate. The resolution was remarkably improved as compared with that obtained in our previous studies. Overall experimental results revealed that the cross-axis coil planet centrifuge is useful for the separation of extremely hydrophilic and ionic compounds, such as water-soluble vitamins, by adding a suitable ion-pair reagent to the polar two-phase solvent system. C1 Nihon Univ, Coll Pharm, Funabashi, Chiba 2748555, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shinomiya, K (reprint author), Nihon Univ, Coll Pharm, 7-7-1 Narashinodai, Funabashi, Chiba 2748555, Japan. NR 12 TC 7 Z9 7 U1 1 U2 8 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2001 VL 24 IS 17 BP 2615 EP 2623 DI 10.1081/JLC-100106089 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 478WZ UT WOS:000171372200005 ER PT J AU Shinomiya, K Kabasawa, Y Ito, Y AF Shinomiya, K Kabasawa, Y Ito, Y TI Countercurrent chromatographic separation of biotic dicarboxylic acids with polar two-phase solvent systems using cross-axis coil planet centrifuge SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID ROTARY SEALS; EFFICIENCY; APPARATUS AB Various aliphatic dicarboxylic acids were separated by counters current chromatography using cross-axis coil planet centrifuge (cross-axis CPC) equipped with a pair of eccentric coil assemblies mounted in an off-center position. Partition coefficients of these samples were optimized by adjusting the volume ratio of a polar two-phase solvent system composed of methyl t-butyl ether/1- butanol/acetonitrile/aqueous 0.1% trifluoroacetic acid., Maleic acid and fumaric acid were separated at a volume ratio, of 5:0:0:5 by the lower aqueous phase mobile, while tartaric acid, succinic acid, and fumaric acid were well resolved by a more polar solvent system at a volume ratio of 2.9:0:2.9:4.3. Using the most polar binary solvent system composed of 1-butanol/water, oxalic acid, malonic acid, and succinic acid were resolved from each other by the lower aqueous phase mobile. The overall results of the present studies indicate that the cross-axis CPC is useful for the separation of various polar organic acids. C1 Nihon Univ, Coll Pharm, Funabashi, Chiba 2748555, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shinomiya, K (reprint author), Nihon Univ, Coll Pharm, 7-7-1 Narashinodai, Funabashi, Chiba 2748555, Japan. EM kshino@pha.nihon-u.sc.jn NR 14 TC 9 Z9 9 U1 2 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2001 VL 24 IS 17 BP 2625 EP 2634 DI 10.1081/JLC-100106090 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 478WZ UT WOS:000171372200006 ER PT J AU Callahan, R Raafat, A AF Callahan, R Raafat, A TI Notch signaling in mammary gland tumorigenesis SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE Notch signaling pathway; mouse mammary tumor virus; transgenic mice; mouse mammary tumorigenesis ID RBP-J-KAPPA; TRUNCATED INT3 GENE; CELL-DIFFERENTIATION; DROSOPHILA NOTCH; EPITHELIAL-CELLS; HUMAN HOMOLOG; NEOPLASTIC TRANSFORMATION; MAMMALIAN NEUROGENESIS; TRANSCRIPTION FACTORS; EMBRYONIC LETHALITY AB The Notch receptor protein and its signaling pathway have been well conserved throughout evolution and appear to be pivotal components in cell fate decisions during development. Recent studies suggest that, depending on the cellular and developmental context, Notch signaling may also affect cell proliferation and programmed cell death. Mammals have four related Notch genes. One of these, designated Notch-4, was found to be a common integration site for the mouse mammary tumor virus in mouse mammary tumors. One consequence of this type of viral integration event is the ectopic expression of the intracellular domain of Notch-4 that corresponds to a gain-of-function mutation. Expression of "activated" Notch-4 in mammary epithelium has profound effects on mammary gland development and tumorigenesis. In this review, we briefly summarize the structure and function of the Notch receptor, as well as the components that comprise and modify the signaling pathway. Finally we discuss the potential role of Notch in mammary gland development and tumorigenesis. C1 NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Callahan, R (reprint author), NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. NR 99 TC 82 Z9 82 U1 0 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD JAN PY 2001 VL 6 IS 1 BP 23 EP 36 DI 10.1023/A:1009512414430 PG 14 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 452FQ UT WOS:000169847200003 PM 11467450 ER PT J AU Wakefield, LM Piek, E Bottinger, EP AF Wakefield, LM Piek, E Bottinger, EP TI TGF-beta signaling in mammary gland development and tumorigenesis SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE TGF-beta s; signal transduction; Smads; MAP kinases; breast cancer; serine-threonine receptor kinases ID GROWTH-FACTOR-BETA; HUMAN-BREAST-CANCER; ACTIVATED PROTEIN-KINASE; RECEPTOR-TYPE-II; EPITHELIAL-CELLS; TRANSFORMING GROWTH-FACTOR-BETA-1; MICROSATELLITE INSTABILITY; TRANSCRIPTION FACTOR; MUTATION ANALYSIS; MCF-7 CELLS AB Ligands of the TGF-beta superfamily are unique in that they signal through transmembrane receptor serine-threonine kinases, rather than tyrosine kinases. The receptor complex couples to a signal transduction pathway involving a novel family of proteins, the Smads. On phosphorylation, Smads translocate to the nucleus where they modulate transcriptional responses. However, TGF-betas can also activate the mitogen-activated protein kinase (MAPK)(4) pathway, and the different biological responses to TGF-beta depend to varying degrees on activation of either or both of these two pathways. The Smad pathway is a nexus for cross-talk with other signal transduction pathways and for modulation by many different interacting proteins. Despite compelling evidence that TGF-beta has tumor suppressor activity in the mammary gland, neither TGF-beta receptors nor Smads are genetically inactivated in human breast cancer, though receptor expression is reduced. Possible reasons are discussed in relation to the dual role of TGF-beta as tumor suppressor and oncogene. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA. RP Wakefield, LM (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NR 76 TC 79 Z9 85 U1 1 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD JAN PY 2001 VL 6 IS 1 BP 67 EP 82 DI 10.1023/A:1009568532177 PG 16 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 452FQ UT WOS:000169847200006 PM 11467453 ER PT J AU Siwarski, D Kim, J Diaw, L Huppi, K AF Siwarski, D Kim, J Diaw, L Huppi, K TI Identification of a transcriptionally compromised allele of c-MYC in a North American family SO JOURNAL OF MEDICAL GENETICS LA English DT Letter ID NON-HODGKINS-LYMPHOMA; BURKITTS-LYMPHOMA; CODING REGION; MUTATIONS; GENE; TRANSACTIVATION; INHIBITION; YIN-YANG-1; ONCOGENE; PROMOTER C1 NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Huppi, K (reprint author), NCI, Genet Lab, NIH, Bldg 37,Room 2B-21, Bethesda, MD 20892 USA. NR 22 TC 0 Z9 1 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JAN PY 2001 VL 38 IS 1 BP 47 EP 49 DI 10.1136/jmg.38.1.47 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 389AN UT WOS:000166215500009 PM 11332400 ER EF