FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Chiang, YH Borlongan, CV Zhou, FC Hoffer, BJ Wang, Y AF Chiang, Yung-Hsiao Borlongan, Cesario V. Zhou, Feng C. Hoffer, Barry J. Wang, Yun TI Transplantation of fetal kidney cells: Neuroprotection and neuroregeneration SO CELL TRANSPLANTATION LA English DT Review DE fetal kidney; Parkinson's disease; stroke ID MIDBRAIN DOPAMINERGIC-NEURONS; NEUROTROPHIC FACTOR PROTECTS; BONE MORPHOGENETIC PROTEINS; CEREBRAL-ARTERY OCCLUSION; VENTRAL MESENCEPHALIC GRAFTS; KAINATE-INDUCED EXCITATION; FACTOR MESSENGER-RNA; MICE LACKING GDNF; IN-VIVO; NERVOUS-SYSTEM AB Various trophic factors in the transforming growth factor-beta (TGF-beta) superfamily have been reported to have neuroprotective and neuroregenerative effects. Intracerebral administration of glial cell line-derived neurotrophic factor (GDNF) or bone morphogenetic proteins (BMPs), both members of the TGF-beta family, reduce ischemia- or 6-hydroxydopamine (6-OHDA)-induced injury in adult rat brain. Because BMPs and GDNF are highly expressed in fetal kidney cells, transplantation of fetal kidney tissue could serve as a cellular reservoir for such molecules and protect against neuronal injury induced by ischemia, neurotoxins, or reactive oxygen species. In this review, we discuss preclinical evidence for the efficacy of fetal kidney cell transplantation in neuroprotection and regeneration models. C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Tri Serv Gen Hosp, Natl Def Med Ctr, Taipei, Taiwan. Med Coll Georgia, Dept Neurol, Augusta, GA 30912 USA. Augusta VA Med Ctr, Augusta, GA USA. Indiana Univ, Sch Med, Dept Anat & Cell Biol, Indianapolis, IN USA. Indiana Univ, Sch Med, Stark Neurosci Res Inst, Indianapolis, IN USA. RP Wang, Y (reprint author), NIDA, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ywang@intra.nida.nih.gov OI Borlongan, Cesar/0000-0002-2966-9782 NR 65 TC 18 Z9 18 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2005 VL 14 IS 1 BP 1 EP 9 DI 10.3727/000000005783983304 PG 9 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 080WL UT WOS:000240279100001 PM 15789657 ER PT J AU Atouf, F Choi, Y Fowler, MJ Poffenberger, G Vobecky, J Ta, M Chapman, GB Powers, AC Lumelsky, NL AF Atouf, F Choi, Y Fowler, MJ Poffenberger, G Vobecky, J Ta, M Chapman, GB Powers, AC Lumelsky, NL TI Generation of islet-like hormone-producing cells in vitro from adult human pancreas SO CELL TRANSPLANTATION LA English DT Article DE pancreatic islet transplantation; diabetes; pancreatic stein cells; in vitro culture ID EMBRYONIC STEM-CELLS; ENDOCRINE PROGENITOR CELLS; BETA-CELLS; ENDOTHELIAL-CELLS; PRECURSOR CELLS; MOUSE PANCREAS; DIFFERENTIATION; NEOGENESIS; TRANSPLANTATION; EXPRESSION AB Transplantation of pancreatic islets can provide long-lasting insulin independence for diabetic patients, but the current islet supply is limited. Here we describe a new in vitro System that utilizes adult human pancreatic islet-enriched fractions to generate hormone-producing cells over 3-4 weeks of culture. By labeling proliferating cells with a retrovirus-expressing green fluorescent protein, we show that in this system hormone-producing cells are generated de novo. These hormone-producing cells aggregate to form islet-like cell clusters. The cell clusters, when tested in vitro, release insulin in response to glucose and other secretagogues. After transplantation into immunodeficient, nondiabetic mice, the islet-like cell clusters survive and release human insulin. We propose that this system will be useful as an experimental tool for investigating mechanisms for generating new islet cells from the postnatal pancreas, and for designing strategies to generate physiologically competent pancreatic islet cells ex vivo. C1 NIDDKD, Unit Cellular Differentiat, Islet & Autoimmun Branch, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Med, Div Endocrinol Diabet & Metab, Nashville, TN USA. VA Tennessee Valley Healthcare Syst, Nashville, TN USA. Georgetown Univ, Dept Biol, Washington, DC 20057 USA. RP Lumelsky, NL (reprint author), NIDDKD, Unit Cellular Differentiat, Islet & Autoimmun Branch, NIH, Bldg 10-CRC,Room 5-5940,10 Ctr Dr, Bethesda, MD 20892 USA. EM nadyal@intra.niddk.nih.gov FU NIDDK NIH HHS [DK 62641, DK 55233, DK 63439, DK 20593] NR 49 TC 9 Z9 15 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. PY 2005 VL 14 IS 10 BP 735 EP 748 DI 10.3727/000000005783982602 PG 14 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 006OO UT WOS:000234907000003 PM 16454348 ER PT J AU Wadhwa, S Embree, M Ameye, L Young, MF AF Wadhwa, S Embree, M Ameye, L Young, MF TI Mice deficient in biglycan and fibromodulin as a model for temporomandibular joint osteoarthritis SO CELLS TISSUES ORGANS LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the American-Association-for-Dental-Research CY MAR 09-12, 2005 CL Balitmore, MD SP Amer Assoc Dental Res DE proteoglycans; biglycan; fibromodulin; temporomandibular joint; osteoarthritis ID LEUCINE-RICH PROTEOGLYCANS; EXTRACELLULAR-MATRIX; ARTICULAR-CARTILAGE; CONDYLAR CARTILAGE; MANDIBULAR JOINT; DISORDERS; GROWTH; TMJ; RAT; CHONDROGENESIS AB The temporomandibular joint (TMJ) within the craniofacial complex is unique. In humans, the TMJ can become diseased resulting in severe and disabling pain. There are no cures for TMJ disease at this time. Animal models of TMJ disease are scarce, but some exist, and they are described in this paper. We present in greater detail one animal model that is deficient in two extracellular matrix (ECM) proteoglycans, biglycan (BGN) and fibromodulin (FMOD). Doubly deficient BGN/FMOD mice develop premature TMJ osteoarthritis (OA). In order to explore the mechanistic basis of TMJ-OA, tissues from the condyle of mutant mice were examined for their relative capacity to differentiate and undergo apoptosis. Our data show that there is a redistribution of the critical ECM protein, type 11 Collagen, in mutant mice compared with controls. Mutant mice also have increased apoptosis of the chondrocytes embedded in the articular cartilage. We speculate that the overall imbalance in apoptosis may be the cellular basis for the abnormal production of structural ECM proteins. The abnormal production of the ECM could, in turn, lead to premature erosion and degradation of the articular surface resulting in TMJ-OA. These data underscore the importance of the ECM in controlling the structural integrity of the TMJ. Copyright (c) 2005 S. Karger AG, Basel. C1 Univ Connecticut, Hlth Ctr, Sch Dent Med, Div Orthodont, Farmington, CT 06030 USA. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. Nestle Res Ctr, Dept Nutr, Lausanne, Switzerland. RP Wadhwa, S (reprint author), Univ Connecticut, Hlth Ctr, Sch Dent Med, Div Orthodont, Farmington, CT 06030 USA. EM wadhwa@uchc.edu FU Intramural NIH HHS NR 40 TC 27 Z9 27 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2005 VL 181 IS 3-4 BP 136 EP 143 DI 10.1159/000091375 PG 8 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 035RZ UT WOS:000237020700003 PM 16612079 ER PT J AU Boskey, AL Young, MF Kilts, T Verdelis, K AF Boskey, AL Young, MF Kilts, T Verdelis, K TI Variation in mineral properties in normal and mutant bones and teeth SO CELLS TISSUES ORGANS LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the American-Association-for-Dental-Research CY MAR 09-12, 2005 CL Balitmore, MD SP Amer Assoc Dental Res DE hydroxyapatite; mineralization; micro-computed tomography; Fourier transform infrared microspectroscopy; biglycan-knockout mice ID OSTEOCALCIN-DEFICIENT MICE; DENTIN MATRIX PROTEIN-1; TOOTH CROWN SIZE; HYDROXYAPATITE FORMATION; TARGETED DISRUPTION; BIGLYCAN GENE; IN-VIVO; DECORIN; PROTEOGLYCANS; TISSUES AB Hydroxyapatite mineral is deposited in an organized fashion in the matrices of bones and teeth. The amount of mineral present, the composition of the mineral, and the size of the mineral crystals varies with both tissue and animal age, diet, health status, and the tissue being examined. Here, we review methods for measuring these differences in mineral properties and provide some illustrations from bones and teeth of animals in which the small leucine-rich proteoglycans (biglycan and decorin) were ablated. Differences in mineral properties between biglycan-deficient bones and teeth are related to the functions of this small proteoglycan in these tissues. Copyright (c) 2005 S. Karger AG, Basel. C1 Hosp Special Surg, Musculoskeletal Integr Program, Mineralized Tissue Res Lab, New York, NY 10021 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Boskey, AL (reprint author), Hosp Special Surg, Musculoskeletal Integr Program, Mineralized Tissue Res Lab, 535 E 70th St, New York, NY 10021 USA. EM boskeya@hss.edu OI Boskey, Adele/0000-0002-6181-2219 FU Intramural NIH HHS; NIDCR NIH HHS [K08 DE 467, DE04141] NR 43 TC 29 Z9 29 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2005 VL 181 IS 3-4 BP 144 EP 153 DI 10.1159/000091376 PG 10 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 035RZ UT WOS:000237020700004 PM 16612080 ER PT J AU Holmbeck, K AF Holmbeck, K TI Collagenase in cranial morphogenesis SO CELLS TISSUES ORGANS LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the American-Association-for-Dental-Research CY MAR 09-12, 2005 CL Balitmore, MD SP Amer Assoc Dental Res DE membrane type 1 matrix metalloproteinase; cartilage remodeling; collagenase; cranicifacial morphogenesis ID CATHEPSIN-K DEFICIENCY; MATRIX-METALLOPROTEINASE; ENDOCHONDRAL OSSIFICATION; COLLAGENOLYTIC ACTIVITY; BONE-FORMATION; CELL BIOLOGY; GELATINASE-A; MICE LACKING; CARTILAGE; GROWTH AB Collagen is the most abundant extracellular matrix protein in connective tissues of higher animals. The growth of connective tissues is intimately linked to the ability to model and remodel the collagen-rich matrices of the organism at critical points during development and growth to allow expansion and adaptation of tissue interfaces. The mammalian cranium is one such place where collagen remodeling is required for proper growth, and this review explores the consequences of abrogated collagen remodeling as they materialize in a mouse model deficient for the membrane type 1 matrix metalloproteinase. Copyright (c) 2005 S. Karger AG, Basel. C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, Matrix Metalloproteinase Unit, NIH, Bethesda, MD 20892 USA. RP Holmbeck, K (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, Matrix Metalloproteinase Unit, NIH, 30 Convent Dr Bldg 30 Room 125 MSC 4380, Bethesda, MD 20892 USA. EM kenn.holmbeck@nih.gov NR 54 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2005 VL 181 IS 3-4 BP 154 EP 165 DI 10.1159/000091377 PG 12 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 035RZ UT WOS:000237020700005 PM 16612081 ER PT J AU Fukumoto, S Yamada, A Nonaka, K Yamada, Y AF Fukumoto, S Yamada, A Nonaka, K Yamada, Y TI Essential roles of ameloblastin in maintaining ameloblast differentiation and enamel formation SO CELLS TISSUES ORGANS LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the American-Association-for-Dental-Research CY MAR 09-12, 2005 CL Balitmore, MD SP Amer Assoc Dental Res DE ameloblastin; amelogenin; enamel matrix protein ID TOOTH DEVELOPMENT; EXTRACELLULAR-MATRIX; GENE; AMELOGENIN; CLONING; EXPRESSION; PROTEINS; MICE; IMMUNOLOCALIZATION; TRANSCRIPTION AB During tooth development, dental epithelial cells interact with extracellular matrix components, such as the basement membrane and enamel matrix. Ameloblastin, an enamel matrix protein, plays a crucial role in maintaining the ameloblast differentiation state and is essential for enamel formation. Ameloblastin-null mice developed severe enamel hypoplasia. In mutant mice, dental epithelial cells started to differentiate into ameloblasts, but ameloblasts soon lost cell polarity, proliferated, and formed multiple cell layers, indicative of some aspects of preameloblast phenotypes. In addition, the expression of amelogenin, another component of the enamel matrix, was specifically reduced in mutant anneloblasts. More than 20% of amelobastin-null mice developed odontogenic tumors. We also found that recombinant ameloblastin specifically bound to anneloblasts and inhibited proliferation of dental epithelial cells. These results suggest that ameloblastin is an important regulator to maintain the differentiation state of anneloblasts. Copyright (c) 2005 S. Karger AG, Basel. C1 Kyushu Univ, Fac Dent Sci, Div Oral Hlth Growth & Dev, Sect Pediat Dent,Higashi Ku, Fukuoka 8128582, Japan. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. RP Fukumoto, S (reprint author), Kyushu Univ, Fac Dent Sci, Div Oral Hlth Growth & Dev, Sect Pediat Dent,Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. EM fukumoto@dent.kyushu-u.ac.jp NR 39 TC 41 Z9 44 U1 2 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2005 VL 181 IS 3-4 BP 189 EP 195 DI 10.1159/000091380 PG 7 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 035RZ UT WOS:000237020700008 PM 16612084 ER PT J AU Gibson, CW Kulkarni, AB Wright, JT AF Gibson, CW Kulkarni, AB Wright, JT TI The use of animal models to explore amelogenin variants in amelogenesis imperfecta SO CELLS TISSUES ORGANS LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the American-Association-for-Dental-Research CY MAR 09-12, 2005 CL Balitmore, MD SP Amer Assoc Dental Res DE amelogenin; amelogenesis imperfecta; enamel proteins; Arhgap6; nested genes ID GENE SPLICE PRODUCTS; TRANSLATION PRODUCT; MOLAR DEVELOPMENT; MATRIX PROTEINS; MESSENGER-RNA; RAT INCISOR; IN-VIVO; ENAMEL; EXPRESSION; MUTATION AB Amelogenin proteins are secreted by ameloblast cells during tooth development. Because of extensive alternative splicing of the amelogenin primary RNA transcript, and because systematic proteolysis results in many additional peptides during enamel maturation, it has been difficult to assign function to individual amelogenins. Targeted deletions and transgenic mice have been generated in order to better understand amelogenin protein function in vivo. From these murine models, we have determined that amelogenins are responsible for normal enamel thickness and structure, but not for initiation of enamel mineral formation at the dentin-enamel junction. Although it is now clear that the amelogenin (AmelX) gene exists in a nested orientation and that AmelX is expressed at a low level in various developing tissues, the significance of these findings is incompletely understood. Future studies are expected to answer remaining questions concerning structure/function relationships among these 'enamel proteins'. Copyright (c) 2005 S. Karger AG, Basel. C1 Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, Funct Genom Unit, NIH, Bethesda, MD USA. Univ N Carolina, Sch Dent, Dept Pediat Dent, Chapel Hill, NC USA. RP Gibson, CW (reprint author), Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, 240 S 40th St, Philadelphia, PA 19104 USA. EM gibson@biochem.dental.upenn.edu FU Intramural NIH HHS; NIDCR NIH HHS [DE011089] NR 48 TC 7 Z9 8 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2005 VL 181 IS 3-4 BP 196 EP 201 DI 10.1159/000091381 PG 6 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 035RZ UT WOS:000237020700009 PM 16612085 ER PT J AU Yewdell, JW AF Yewdell, JW TI Serendipity strikes twice: The discovery and rediscovery of defective ribosomal products (DRiPS) SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article DE defective ribosomal products; immunity to viruses; ubiquitin-proteasome pathway; rapidly degraded proteins ID NEWLY SYNTHESIZED PROTEINS; CYTOTOXIC LYMPHOCYTES-T; CLASS-I MOLECULES; DEGRADATION; PEPTIDES; CELLS; FIBROBLASTS; PROTEASOME; COLLAGEN AB Here I recount how the remarkably large fraction of rapidly degraded nascent proteins was discovered through serendipity not once, but twice. This story is used as a canvas for discussing how the imperfections in human nature retard scientific progress. C1 NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. EM jyewdell@nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 18 TC 14 Z9 14 U1 0 U2 2 PU CELLULAR & MOLECULAR BIOLOGY PI NOISY-LE-GRAND PA PROF R WEGMANN RESIDENCE HAUSSMANN 1 AVENUE DU PAVE NEUF, 93160 NOISY-LE-GRAND, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PY 2005 VL 51 IS 7 BP 635 EP 641 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 034OM UT WOS:000236939100009 PM 16359615 ER PT J AU Acharya, U Acharya, JK AF Acharya, U Acharya, JK TI Enzymes of sphingolipid metabolism in Drosophila melanogaster SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Drosophila; sphingolipids; molecular genetics; metabolism ID LONG-CHAIN BASE; INDUCED MALE RECOMBINATION; CALLIPHORA-VICINA INSECTA; LONGEVITY-ASSURANCE GENE; PROGRAMMED CELL-DEATH; P-ELEMENT INSERTIONS; SERINE PALMITOYLTRANSFERASE; NEUTRAL SPHINGOMYELINASE; SACCHAROMYCES-CEREVISIAE; PHOTORECEPTOR DEGENERATION AB Sphingolipids are important structural components of membranes that delimit the boundaries of cellular compartments, cells and organisms. They play an equally important role as second messengers, and transduce signals across or within the compartments they define to initiate physiological changes during development, differentiation and a host of other cellular events. For well over a century Drosophila melanogaster has served as a useful model organism to understand some of the fundamental tenets of development, differentiation and signaling in eukaryotic organisms. Directed approaches to study sphingolipid biology in Drosophila have been initiated only recently. Nevertheless, earlier phenotypic studies conducted on genes of unknown biochemical function have recently been recognized as mutants of enzymes of sphingolipid metabolism. Genome sequencing and annotation have aided the identification of homologs of recently discovered genes. Here we present an overview of studies on enzymes of the de novo sphingolipid biosynthetic pathway, known mutants and their phenotypic characterization in Drosophila. C1 NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA. RP Acharya, JK (reprint author), NCI, Lab Prot Dynam & Signaling, Room 22-6,Bldg 560,1050 Boyle St, Frederick, MD 21702 USA. EM acharyaj@mail.ncifcrf.gov NR 140 TC 37 Z9 38 U1 1 U2 6 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD JAN PY 2005 VL 62 IS 2 BP 128 EP 142 DI 10.1007/s00018-004-4254-1 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 897DA UT WOS:000226983000002 PM 15666085 ER PT J AU Drecktrah, D Knodler, LA Galbraith, K Steele-Mortimer, O AF Drecktrah, D Knodler, LA Galbraith, K Steele-Mortimer, O TI The Salmonella SPI1 effector SopB stimulates nitric oxide production long after invasion SO CELLULAR MICROBIOLOGY LA English DT Article ID ENTERICA SEROVAR TYPHIMURIUM; III SECRETION SYSTEM; NADPH PHAGOCYTE OXIDASE; PATHOGENICITY ISLAND 2; HOST-CELLS; EPITHELIAL-CELLS; MOLECULAR CHARACTERIZATION; INTRACELLULAR SALMONELLA; ANTIMICROBIAL ACTIONS; SYNTHASE EXPRESSION AB The ability of Salmonella enterica to invade and replicate within host cells depends on two type III secretion systems (TTSSs) encoded on pathogenicity islands 1 and 2 (SPI1 and SPI2). The current paradigm holds that these systems translocate two classes of effectors that operate sequentially and independently. In essence, the SPI1 TTSS mediates early events (i.e. invasion) whereas the SPI2 TTSS mediates post-invasion processes (i.e. replication, vacuole maturation). Contrary to this model, we have found in infected macrophages that a SPI1 effector, SopB/SigD, increased inducible nitric oxide synthase levels and nitric oxide production, host cell process previously known only to be a target of the SPI2 TTSS. Furthermore, SopB protein and message persist many hours after invasion. Our findings reveal an unanticipated potential for dialogue between the SPI1 and SPI2 TTSS and the host cell response. C1 NIAID, Intracellular Parasites Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Steele-Mortimer, O (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. EM omortimer@niaid.nih.gov NR 37 TC 59 Z9 62 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD JAN PY 2005 VL 7 IS 1 BP 105 EP 113 DI 10.1111/j.1462-5822.2004.00436.x PG 9 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 882RV UT WOS:000225956900010 PM 15617527 ER PT J AU Shivakrupa, R Linnekin, D AF Shivakrupa, R Linnekin, D TI Lyn contributes to regulation of multiple Kit-dependent signaling pathways in murine bone marrow mast cells SO CELLULAR SIGNALLING LA English DT Article DE Kit; stem cell factor; Lyn; tyrosine kinases; signal transduction; hematopoiesis ID SRC FAMILY KINASE; P56/P53(LYN) TYROSINE KINASE; C-KIT; HEMATOPOIETIC-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHORYLATION SITE; ANTIGEN RECEPTOR; MAMMALIAN-CELLS; DEFICIENT MICE; PI 3-KINASE AB SCF induces autophosphorylation of Kit and activates a variety of signaling components including Jnks, Erks, PI 3 Kinase, the JAK-Stat pathway and members of the Src family. Previously we showed that Lyn is activated at multiple points during SCF-induced cell cycle progression and contributes to SCF-mediated growth, chemotaxis and internalization of Kit. However, the Kit-dependent biochemical events that require Lyn are unknown. In this study, we used Lyn-deficient bone marrow mast cells (BMMC) to examine the contribution of this Src family member to tyrosine phosphorylation of Kit and SCF-induced activation of Jnks, Akt, Stat3 and Erks. Although surface expression of Kit was increased in Lyn-deficient BMMC, SCF-induced phosphorylation and growth was reduced compared to wild-type BMMC. Downstream of Kit, SCF-induced activation of Jnks was markedly reduced in Lyn-deficient BMMC. Further, Lyn was required for SCF-induced tyrosine phosphorylation of Stat3. Interestingly, Kit was constitutively associated with PI 3 Kinase in Lyn-deficient BMMC and this correlated with constitutive phosphorylation of Akt. This was in marked contrast to wild-type BMMC, where both these events were induced by SCF. These data indicate that in BMMC, Lyn contributes to SCF-induced phosphorylation of Kit, as well as phosphorylation of Jnks and Stat3. In contrast, Lyn may negatively regulate the PI 3 Kinase/Akt pathway. The opposing effects of Lyn on these signaling pathways may explain the pleiotropic effects ascribed to this Src family member in the literature. (C) 2004 Elsevier Inc. All rights reserved. C1 NCI, Basic Res Lab, Canc Res Ctr, Frederick, MD 21702 USA. RP Shivakrupa, R (reprint author), NCI, Basic Res Lab, Canc Res Ctr, Bldg 567,Room 226, Frederick, MD 21702 USA. EM shiva_krupa@hotmail.com NR 50 TC 32 Z9 33 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD JAN PY 2005 VL 17 IS 1 BP 103 EP 109 DI 10.1016/j.cellsig.2004.06.004 PG 7 WC Cell Biology SC Cell Biology GA 861XV UT WOS:000224452800012 PM 15451030 ER PT J AU Pokorski, JK Nam, JM Vega, RA Mirkin, CA Appella, DH AF Pokorski, JK Nam, JM Vega, RA Mirkin, CA Appella, DH TI Cyclopentane-modified PNA improves the sensitivity of nanoparticle-based scanometric DNA detection SO CHEMICAL COMMUNICATIONS LA English DT Article ID PEPTIDE NUCLEIC-ACID; BINDING-AFFINITY; POINT MUTATION; LABEL-FREE; PROBES; MICROARRAYS; STABILITY; BIOSENSOR AB trans-Cyclopentane-modified PNA has been successfully utilized as a target capture strand to improve the detection limit of a known DNA detection assay, and provide high levels of mismatch discrimination. C1 Northwestern Univ, Dept Chem, Evanston, IL USA. NIDDK, NIH, Bioorgan Chem Lab, Bethesda, MD USA. Northwestern Univ, Inst Nanotechnol, Evanston, IL USA. RP Appella, DH (reprint author), Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL USA. EM appellad@niddk.nih.gov RI Mirkin, Chad/E-3911-2010; OI Pokorski, Jonathan/0000-0001-5869-6942 NR 19 TC 18 Z9 18 U1 0 U2 7 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2005 IS 16 BP 2101 EP 2103 DI 10.1039/b418383e PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 918PD UT WOS:000228559200009 PM 15846413 ER PT J AU Wang, GP Song, EQ Xie, HY Zhang, ZL Tian, ZQ Zuo, C Pang, DW Wu, DC Shi, YB AF Wang, GP Song, EQ Xie, HY Zhang, ZL Tian, ZQ Zuo, C Pang, DW Wu, DC Shi, YB TI Biofunctionalization of fluorescent-magnetic-bifunctional nanospheres and their applications SO CHEMICAL COMMUNICATIONS LA English DT Article ID QUANTUM DOTS; APOPTOSIS; NANOCOMPOSITES; NANOPARTICLES; NANOCRYSTALS; CELLS; BEADS AB Hydrazide-containing bifunctional nanospheres were covalently coupled on the surface with IgG, avidin, and biotin, to generate novel fluorescent-magnetic-biotargeting trifunctional nanospheres, which can be used in a number of biomedical applications, including visual sorting and manipulation of apoptotic cells as demonstrated here. C1 Wuhan Univ, Coll Chem & Mol Sci, State Key Lab Virol, Wuhan 430072, Peoples R China. Beijing Inst Technol, Sch Life Sci & Technol, Beijing 100081, Peoples R China. Xian Jiaotong Univ, Sch Life Sci & Technol, Xian 710049, Peoples R China. NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Pang, DW (reprint author), Wuhan Univ, Coll Chem & Mol Sci, State Key Lab Virol, Wuhan 430072, Peoples R China. EM dwpang@whu.edu.cn RI Zhang, Zhi-Ling/B-3135-2010; Tian, Zhi-Quan/K-5304-2012; OI Zhang, Zhi-Ling/0000-0001-7807-2264; Wu, Daocheng/0000-0002-6183-539X FU Intramural NIH HHS NR 20 TC 80 Z9 85 U1 4 U2 32 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2005 IS 34 BP 4276 EP 4278 DI 10.1039/b508075d PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 957JK UT WOS:000231365900006 PM 16113720 ER PT J AU Talanova, GG Roper, ED Buie, NM Gorbunova, MG Bartsch, RA Talanov, VS AF Talanova, GG Roper, ED Buie, NM Gorbunova, MG Bartsch, RA Talanov, VS TI Novel fluorogenic calix[4] arene-bis( crown-6-ether) for selective recognition of thallium(I) SO CHEMICAL COMMUNICATIONS LA English DT Article ID FLUORESCENT MOLECULAR SENSORS; BINDING-PROPERTIES; POTASSIUM-IONS; CESIUM; 1,3-ALTERNATE; COMPLEXES; SWITCHES; CATIONS; PROBE AB A new fluorogenic, dansyl group-containing derivative of 1,3-alternate calix[4]arene-bis(crown-6-ether) provides optical recognition of Tl+ with selectivity over many other metal cations, including Na+, K+, Ca2+, Ag+, Hg2+ and Pb2+, and embodies the first example of a calixarene-based fluorescent Tl+-chemosensor. C1 Howard Univ, Dept Chem, Washington, DC 20059 USA. Oak Ridge Natl Lab, Div Chem Sci, Oak Ridge, TN 37831 USA. Texas Tech Univ, Dept Chem & Biochem, Lubbock, TX 79409 USA. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Talanova, GG (reprint author), Howard Univ, Dept Chem, 525 Coll St,NW, Washington, DC 20059 USA. EM gtalanova@howard.edu NR 19 TC 33 Z9 33 U1 0 U2 7 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2005 IS 45 BP 5673 EP 5675 DI 10.1039/b510348g PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 986OE UT WOS:000233458800022 PM 16292386 ER PT J AU Shi, ZD Karki, RG Worthy, KM Bindu, LK Nicklaus, MC Fisher, RJ Burke, TR AF Shi, ZD Karki, RG Worthy, KM Bindu, LK Nicklaus, MC Fisher, RJ Burke, TR TI Utilization of a common pathway for the synthesis of high affinity macrocyclic Grh2 SH2 domain-binding peptide mimetics that differ in the configuration at one ring junction SO CHEMISTRY & BIODIVERSITY LA English DT Article ID GRB2; DESIGN; INHIBITOR; LIGANDS AB As typified by 2-((9S,10S,14R,18S)-18-(2-amino-2-oxoethyl)-14-[(5-methyl-1H-indol-1-yl)methyl]-8,17,20-trioxo- 10-[4-(phosphonomethyl)phenyl]-7,16,19-triazaspiro[5.14]icos-11-en-9-yl] acetic acid ((14R)-1b), ring-closing methathesis-derived macrocyclic tetrapeptide mimetics have recently been reported that bind with high affinity to Grb2 SH2 domains in both extracellular and whole-cell assays. The synthetic complexity of this class of agents limits further therapeutic development. Although a significant component of this synthetic complexity arises from the presence of three stereogenic centers, C(9) (S), C(10) (S), and C(14) (R), it is unclear whether stereoselective introduction of defined configuration at C(14) is required for high-affinity binding. Reported herein is a synthetic route to these macrocycles lacking stereoselectivity in the formation of the C(14) ring junction, which is four synthetic steps shorter than the original stereoselective synthesis. Separation of C(14)-epimers obtained by this approach was achieved by preparative HPLC. Molecular-dynamics studies of ligands bound to the Grb2 SH2 domain protein indicated that the (14R)-configuration should display more-favorable interactions with the protein relative to the (14S)-epimer. Indeed, although surface-plasmon-resonance-derived binding constants to Grb2 SH2 domain protein indicated that the affinity of the (14R)-epimer (K-D = 4.8 nm) is greater than that of the (14S)-epimer (K-D = 11 rim), it is only marginally so. Therefore, little affinity would be lost through a non-stereoselective synthesis of the C(14)-center. Further studies are in progress to explore reduced structural complexity at the C(14)-center. C1 NCI, Med Chem Lab, CCR, NIH, Ft Detrick, MD 21702 USA. SAIC Frederick, Prot Chem Lab, Ft Detrick, MD 21702 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, CCR, NIH, POB B,376 Boyles St, Ft Detrick, MD 21702 USA. EM tburkw@helix.nih.gov RI Fisher, Robert/B-1431-2009; Nicklaus, Marc/N-4183-2014; Burke, Terrence/N-2601-2014 NR 14 TC 5 Z9 5 U1 0 U2 0 PU VERLAG HELVETICA CHIMICA ACTA AG PI ZURICH PA HOFWIESENSTRASSE 26, POSTFACH, CH-8042 ZURICH, SWITZERLAND SN 1612-1872 J9 CHEM BIODIVERS JI Chem. Biodivers. PY 2005 VL 2 IS 4 BP 447 EP 456 DI 10.1002/cbdv.200590024 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA 921MZ UT WOS:000228770000002 PM 17191992 ER PT J AU Liu, YS Shreder, KR Gai, WZ Corral, S Ferris, DK Rosenblum, JS AF Liu, YS Shreder, KR Gai, WZ Corral, S Ferris, DK Rosenblum, JS TI Wortmannin, a widely used phosphoinositide 3-kinase inhibitor, also potently inhibits mammalian polo-like kinase SO CHEMISTRY & BIOLOGY LA English DT Article ID SERINE HYDROLASE ACTIVITIES; ACTIVITY-BASED PROBES; COMPLEX PROTEOMES; CELL-CYCLE; SACCHAROMYCES-CEREVISIAE; PROGNOSTIC-SIGNIFICANCE; PLK EXPRESSION; CANCER-CELLS; IN-VITRO; ENZYME AB Polo-like kinases (PLKs) play critical roles throughout mitosis. Here, we report that wortmannin, which was previously thought to be a highly selective inhibitor of phosphoinositide (PI) 3-kinases, is a potent inhibitor of mammalian PLK1. Observation of the wortmannin-PLK1 interaction was enabled by a tetra-methylrhodamine-wortmannin conjugate (AX7503) that permits rapid detection of PLK1 activity and expression in complex proteomes. Importantly, we show that wortmannin inhibits PLK1 activity in an in vitro kinase assay with an IC50 of 24 nM and when incubated with intact cells. Taken together, our results indicate that, at the concentrations of wortmannin commonly used to inhibit PI 3-kinases, PLK1 is also significantly inhibited. C1 ActivX Biosci Inc, La Jolla, CA 92037 USA. NCI, Frederick Canc Res & Dev Ctr, Biol Mech Sect, Lab Leukocyte Biol, Frederick, MD 21702 USA. RP Liu, YS (reprint author), ActivX Biosci Inc, 11025 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM yongshengl@activx.com OI Rosenblum, Jonathan/0000-0002-7318-0896 FU NCI NIH HHS [2R44 CA 097462-02] NR 54 TC 122 Z9 128 U1 2 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD JAN PY 2005 VL 12 IS 1 BP 99 EP 107 DI 10.1016/j.chembiol.2004.11.009 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 894NI UT WOS:000226798200014 PM 15664519 ER PT S AU Cortez, KJ Jackson, JO Kottilil, S AF Cortez, KJ Jackson, JO Kottilil, S BE Schwiebert, LM TI Chemokines and chemokine receptors in infectious disease SO CHEMOKINES, CHEMOKINE RECEPTORS, AND DISEASE SE Current Topics in Membranes LA English DT Review; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; SMALL-MOLECULE INHIBITOR; T-TROPIC HIV-1; TOXOPLASMA-GONDII INFECTION; PLATELET-ACTIVATING-FACTOR; CELL-SURFACE ASSOCIATION; CENTRAL-NERVOUS-SYSTEM; SCH-C SCH-351125; IN-VITRO C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Cortez, KJ (reprint author), NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 138 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1063-5823 BN 0-12-153355-7 J9 CURR TOP MEMBR JI Curr. Top. Membr. PY 2005 VL 55 BP 289 EP 329 DI 10.1016/S1063-5823(04)55011-1 PG 41 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BDG04 UT WOS:000233334000011 ER PT J AU Morales, OG Henry, ME Nobler, MS Wassermann, EM Lisanby, SH AF Morales, OG Henry, ME Nobler, MS Wassermann, EM Lisanby, SH TI Electroconvulsive therapy and repetitive transcranial magnetic stimulation in children and adolescents: a review and report of two cases of epilepsia partialis continua SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID LEFT TEMPOROPARIETAL CORTEX; SEIZURE THERAPY; MOTOR CORTEX; ELECTRODE PLACEMENT; YOUNG-PEOPLE; ECT; DEPRESSION; BRAIN; THRESHOLD AB Brain stimulation for the treatment of psychiatric disorders has received increasing attention over the past decade. The introduction of experimental means to stimulate the brain noninvasively with magnetic fields not only has raised interest in these novel means of modulating brain activity but also has refocused attention on a mainstay in the treatment of severe major depression and other disorders (electroconvulsive therapy). This article reviews the current state of knowledge concerning the use electroconvulsive therapy, repetitive transcranial magnetic stimulation, and magnetic seizure therapy in children and adolescents. Two cases of medically intractable epilepsia partialis continua are presented to add to the limited literature on the use of repetitive transcranial magnetic stimulation in children and adolescents and illustrate the concept of using functional neuroimaging results to target the application of a focal intervention in an attempt to dampen hyperactive regions of the cortex. C1 New York State Psychiat Inst & Hosp, Dept Biol Psychiat, Magnet Brain Stimulat Lab, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. McLean Med Ctr, ECT Serv, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. NIMH, NINDS, Brain Stimulat Unit, Bethesda, MD 20892 USA. RP Morales, OG (reprint author), New York State Psychiat Inst & Hosp, Dept Biol Psychiat, Magnet Brain Stimulat Lab, 1051 Riverside Dr,Box 126, New York, NY 10032 USA. EM om2102@columbia.edu FU NIMH NIH HHS [K08 MH064175-03, K08 MH01577, R01 MH60884, T32 MH020004] NR 54 TC 28 Z9 28 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JAN PY 2005 VL 14 IS 1 BP 193 EP + DI 10.1016/j.chc.2004.07.010 PG 20 WC Psychiatry SC Psychiatry GA 883CS UT WOS:000225988400012 PM 15564059 ER PT J AU Dumas, F Bigoni, F Stone, G Sineo, L Stanyon, R AF Dumas, F Bigoni, F Stone, G Sineo, L Stanyon, R TI Mapping genomic rearrangements in titi monkeys by chromosome flow sorting and multidirectional in-situ hybridization SO CHROMOSOME RESEARCH LA English DT Article DE chromosome painting; comparative genomics; phylogeny; primates; speciation ID NEW-WORLD MONKEYS; DIPLOID NUMBER 2N=16; CALLICEBUS-PERSONATUS; CYTOGENETIC ANALYSIS; SAGUINUS-OEDIPUS; PRIMATES; PLATYRRHINI; KARYOTYPE; CEBIDAE; MOLOCH AB We developed chromosome painting probes for Callicebus pallescens from flow-sorted chromosomes and used multidirectional chromosome painting to investigate the genomic rearrangements in C. cupreus and C. pallescens. Multidirectional painting provides information about chromosomal homologies at the subchromosomal level and rearrangement break points, allowing chromosomes to be used as cladistic markers. Chromosome paints of C. pallescens were hybridized to human metaphases and 43 signals were detected. Then, both human and C. pallescens probes were hybridized to the chromosomes of another titi monkey, C. cupreus. The human chromosome paints detected 45 segments in the haploid karyotype of C. cupreus. We found that all the syntenic associations proposed for the ancestral platyrrhine karyotype are present in C. cupreus and in C. pallescens. The rearrangements differentiating C. pallescens from C. cupreus re one inversion, one fission and three fusions (two tandem and one Robertsonian)that occurred on the C. cupreus lineage. Our results support the hypothesis that karyological evolution in titi monkeys has resulted in reduction in diploid number and that species with higher diploid numbers (with less derived, more ancestral karyotypes)are localized in the centre of the geographic range of the genera, while more derived species appear to occupy the periphery. C1 NCI, MCGP, Comparat Mol Cytogenet Core, Frederick, MD 21701 USA. Univ Palermo, Dipartimento Biol Anim, Palermo, Italy. RP Stanyon, R (reprint author), NCI, MCGP, Comparat Mol Cytogenet Core, Frederick, MD 21701 USA. EM stanyonr@ncifcrf.gov OI Stanyon, Roscoe/0000-0002-7229-1092 NR 49 TC 16 Z9 16 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD JAN PY 2005 VL 13 IS 1 BP 85 EP 96 DI 10.1007/s10577-005-7063-y PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 911GZ UT WOS:000227991900008 PM 15791414 ER PT J AU Martins, C Roque, L Rodrigues, R Dinis, J Pinto, AE Gelhaus, K Kirsch, IR Dias, S Fonseca, I AF Martins, C. Roque, L. Rodrigues, R. Dinis, J. Pinto, A. E. Gelhaus, K. Kirsch, I. R. Dias, S. Fonseca, I. TI Molecular cytogenetic screening of a novel salivary gland cell line derived from a carcinoma ex-pleomorphic adenoma carrying PLAG1 gene rearrangements SO CHROMOSOME RESEARCH LA English DT Meeting Abstract C1 [Martins, C.; Roque, L.; Rodrigues, R.; Dinis, J.; Dias, S.] Inst Portugues Oncol Francisco Gentil, CIPM, Lisbon, Portugal. [Pinto, A. E.; Fonseca, I.] Inst Portugues Oncol Francisco Gentil, Serv Anat Patol, Lisbon, Portugal. [Gelhaus, K.; Kirsch, I. R.] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PY 2005 VL 13 BP 91 EP 92 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA V81JY UT WOS:000205501400215 ER PT J AU Salaverria, I Zettl, A Bea, S Ott, G Yang, L Staudt, L Muller-Hermelink, HK Campo, E Rosenwald, A AF Salaverria, I. Zettl, A. Bea, S. Ott, G. Yang, L. Staudt, L. Mueller-Hermelink, H. K. Campo, E. Rosenwald, A. CA LLMPP Consortium TI Secondary genetic alterations with prognostic significance in mantle cell lymphoma SO CHROMOSOME RESEARCH LA English DT Meeting Abstract C1 [Salaverria, I.; Bea, S.; Campo, E.] Univ Barcelona, Hematopathol Sect, Hosp Clin, Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona, Spain. [Zettl, A.; Ott, G.; Mueller-Hermelink, H. K.; Rosenwald, A.] Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany. [Yang, L.; Staudt, L.] NCI, Metab Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PY 2005 VL 13 BP 182 EP 182 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA V81JY UT WOS:000205501400425 ER PT S AU Optican, LM AF Optican, LM BE Ramat, S Straumann, D TI Sensorimotor transformation for visually guided saccades SO CLINICAL AND BASIC OCULOMOTOR RESEARCH: IN HONOR OF DAVID S. ZEE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Clinical and Basic Ocular Motor Research CY JUL 03-05, 2004 CL Siena, ITALY SP Amplifon Italy, Biomed Mangoni, Fdn Ist Neurol C Mondina, Monte Paschi Siena, Univ Degli Studi Siena, Case Western Reserve Univ, John Hopkins Univ, Ludwig Maximilian Univ, Univ Degli Studi Pavia, Univ Zurich DE saccade; control system; modeling; eye movement; brain; superior colliculus; cerebellum; vermis; fastigial nucleus; spatial-temporal transform; sensorimotor transform ID MONKEY SUPERIOR COLLICULUS; CAUDAL FASTIGIAL NUCLEUS; NEURAL-NETWORK MODEL; FRONTAL EYE-FIELD; OCULOMOTOR VERMIS; REVERSIBLE INACTIVATION; DISCHARGE PATTERNS; DISTRIBUTED MODEL; TARGET SELECTION; MACAQUE MONKEYS AB Visually guided movements require the brain to perform a sensorimotor transformation. The key to understanding this transformation is to understand the different roles of the superior colliculus (SC) and cerebellum (CB). The SC has a three-layered structure. Cells in the top layer have visual, but not motor, responses. However, cells in the deeper layers have both visual and motor responses. Thus, for a long time it was thought that the SC encoded both the retinal location of a sensory stimulus and the desired change in eye movement needed to acquire it. However, copious evidence has accumulated that shows that the SC encodes only the retinal location of a visual target, and not the movement needed to foveate it. Thus, the information needed to make accurate movements must come from another part of the brain, which is proposed to be the cerebellum. Here it is shown how the cerebellum could perform the sensorimotor transformation. C1 NEI, Sensorimotor Res Lab, DHHS, NIH, Bethesda, MD 20892 USA. RP Optican, LM (reprint author), NEI, Sensorimotor Res Lab, DHHS, NIH, Bldg 49,Room 2A50, Bethesda, MD 20892 USA. EM LanceOptican@nih.gov NR 45 TC 34 Z9 34 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-565-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1039 BP 132 EP 148 DI 10.1196/annals.1325.013 PG 17 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Ophthalmology SC Science & Technology - Other Topics; Neurosciences & Neurology; Ophthalmology GA BCQ54 UT WOS:000230780400013 PM 15826968 ER PT S AU Sheliga, BM Chen, KJ Fitzgibbon, EJ Miles, FA AF Sheliga, BM Chen, KJ Fitzgibbon, EJ Miles, FA BE Ramat, S Straumann, D TI Short-latency disparity vergence in humans: Evidence for early spatial filtering SO CLINICAL AND BASIC OCULOMOTOR RESEARCH: IN HONOR OF DAVID S. ZEE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Clinical and Basic Ocular Motor Research CY JUL 03-05, 2004 CL Siena, ITALY SP Amplifon Italy, Biomed Mangoni, Fdn Ist Neurol C Mondina, Monte Paschi Siena, Univ Degli Studi Siena, Case Western Reserve Univ, John Hopkins Univ, Ludwig Maximilian Univ, Univ Degli Studi Pavia, Univ Zurich DE missing fundamental; binocular disparity; vergence eye movements ID CORTICAL AREA MST; EYE-MOVEMENTS; ANTICORRELATED STEREOGRAMS; BINOCULAR DISPARITY; STEREOPSIS; DEPTH AB Our study was concerned with the disparity detectors underlying the initial disparity vergence responses (DVRs) that are elicited at ultrashort latencies by binocular disparities applied to large images. DVRs were elicited in humans by applying horizontal disparity to vertical square-wave gratings lacking the fundamental (termed here, the "missing fundamental"). In the frequency domain, a pure square wave is composed of odd harmonics-first, third, fifth, seventh, etc.-such that the third, fifth, seventh, etc., have amplitudes that are one-third, one-fifth, one-seventh, etc., that of the first, and the missing fundamental lacks the first harmonic. The patterns seen by the two eyes have a phase difference of one-quarter wavelength, so the disparity of the features and 4n + 1 harmonics (where n = integer) has one sign (crossed or uncrossed), whereas the 4n - 1 harmonics-including the strongest Fourier component (the third harmonic)-has the opposite sign (uncrossed or crossed): spatial aliasing. The earliest DVRs, recorded with the search-coil technique, had minimum latencies of 70 to 80 ms and were generally in the direction of the third harmonic, that is, uncrossed disparities resulted in convergent eye movements. In other experiments on the DVRs, one eye saw a missing fundamental and the other saw a pure sine wave with the contrast and wavelength of the third harmonic but differing in phase by one-quarter wavelength. This resulted in short-latency vergence in accordance with matching of the third harmonic. These data all indicate the importance of the Fourier components, consistent with early spatial filtering prior to binocular matching. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Sheliga, BM (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50,49 Convent Dr, Bethesda, MD 20892 USA. EM bms@lsr.nei.nih.gov FU NEI NIH HHS [Z01 EY000153-22] NR 15 TC 8 Z9 8 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-565-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1039 BP 252 EP 259 DI 10.1196/annals.1325.024 PG 8 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Ophthalmology SC Science & Technology - Other Topics; Neurosciences & Neurology; Ophthalmology GA BCQ54 UT WOS:000230780400024 PM 15826979 ER PT S AU Chen, KJ Sheliga, BM Fitzgibbon, EJ Miles, FA AF Chen, KJ Sheliga, BM Fitzgibbon, EJ Miles, FA BE Ramat, S Straumann, D TI Initial ocular following in humans depends critically on the Fourier components of the motion stimulus SO CLINICAL AND BASIC OCULOMOTOR RESEARCH: IN HONOR OF DAVID S. ZEE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Clinical and Basic Ocular Motor Research CY JUL 03-05, 2004 CL Siena, ITALY SP Amplifon Italy, Biomed Mangoni, Fdn Ist Neurol C Mondina, Monte Paschi Siena, Univ Degli Studi Siena, Case Western Reserve Univ, John Hopkins Univ, Ludwig Maximilian Univ, Univ Degli Studi Pavia, Univ Zurich DE visual motion; energy-based mechanisms; biphasic temporal impulse response; missing fundamental ID PURSUIT EYE-MOVEMENTS; HUMAN OPTOKINETIC NYSTAGMUS; SHORT-LATENCY; 2ND-ORDER MOTION; APPARENT MOTION; VISUAL-MOTION; STEREOSCOPIC CONTOURS; SPATIAL-FREQUENCIES; BINOCULAR DISPARITY; PERCEPTION AB Visual motion is sensed by low-level (energy-based) and high-level (feature-based) mechanisms. Our interest is in the motion detectors underlying the initial ocular following responses (OFR) that are elicited at ultrashort latencies by sudden motions of large images. OFR were elicited in humans by applying horizontal motion to vertical square-wave gratings lacking the fundamental. In the frequency domain, a pure square wave is composed of the odd harmonics-first, third, fifth, seventh, etc.-such that the third, fifth, seventh, etc., have amplitudes that are one-third, one-fifth, one-seventh, etc., that of the first, and the missing fundamental stimulus lacks the first harmonic. Motion consisted of successive quarter-wavelength steps, so the features and 4n+1 harmonics (where n = integer) shifted forward, whereas the 4n-1 harmonics-including the strongest Fourier component (the third harmonic)-shifted backward (spatial aliasing). Thus, the net Fourier energy and the non-Fourier features moved in opposite directions. Initial OFR, recorded with the search coil technique, had minimum latencies of 60 to 70 ms and were always in the direction of the third harmonic, for example, leftward steps resulted in rightward OFR. Thus, the earliest OFR were strongly dependent on the motion of the major Fourier component, consistent with mediation by oriented spatiotemporal visual filters as in the well-known energy model of motion detection. Introducing interstimulus intervals of 10 to 100 ms (during which the screen was uniform gray) reversed the initial direction of tracking, consistent with extensive neurophysiological and psychophysical data suggesting that the visual input to the motion detectors has a biphasic temporal impulse response. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Miles, FA (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50,49 Convent Dr, Bethesda, MD 20892 USA. EM fam@lsr.nei.nih.gov FU NEI NIH HHS [Z01 EY000153-22] NR 54 TC 15 Z9 16 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-565-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1039 BP 260 EP 271 DI 10.1196/annals.1325.025 PG 12 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Ophthalmology SC Science & Technology - Other Topics; Neurosciences & Neurology; Ophthalmology GA BCQ54 UT WOS:000230780400025 PM 15826980 ER PT J AU Higgins, J Metcalf, JA Stevens, RA Baseler, M Nason, MC Lane, HC Sereti, I AF Higgins, J Metcalf, JA Stevens, RA Baseler, M Nason, MC Lane, HC Sereti, I TI Effects of lymphocyte isolation and timing of processing on detection of CD127 expression on T cells in human immunodeficiency virus-infected patients SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID RECEPTOR EXPRESSION; MONONUCLEAR-CELLS; IL-7 RECEPTOR; HIV-INFECTION; MEMORY CELLS; INTERLEUKIN-7; HOMEOSTASIS; SURVIVAL; THERAPY; BLOOD AB Decreases in the detection of CD127 expression on T cells of human immunodeficiency virus-infected patients by flow cytometry can occur by delayed processing or by peripheral blood mommuclear cell isolation and cryopreservation. These observations should be considered in the interpretation of functional studies and the planning of multicenter clinical trials. C1 NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Clin Serv Program, AIDS Monitoring Lab, Frederick, MD USA. RP Sereti, I (reprint author), NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bldg 10,Room 11B-04,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. EM isereti@niaid.nih.gov FU NCI NIH HHS [N01CO12400, N01-CO-12400] NR 19 TC 6 Z9 7 U1 0 U2 1 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 2005 VL 12 IS 1 BP 228 EP 230 DI 10.1128/CDLI.12.1.228-230.2005 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 901GU UT WOS:000227271800034 PM 15643013 ER PT J AU Hewitt, RE Lissina, A Green, AE Slay, ES Price, DA Sewell, AK AF Hewitt, RE Lissina, A Green, AE Slay, ES Price, DA Sewell, AK TI The bisphosphonate acute phase response: rapid and copious production of proinflammatory cytokines by peripheral blood gamma delta T cells in response to aminobisphosphonates is inhibited by statins SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE bisphosphonates; acute phase response; proinflammatory cytokines; gamma delta T cells; aminobisphosphonates; statins ID NITROGEN-CONTAINING BISPHOSPHONATES; FARNESYL PYROPHOSPHATE SYNTHASE; ACTIVATION IN-VITRO; NONPEPTIDE ANTIGENS; DIPHOSPHATE SYNTHASE; PAGETS-DISEASE; AIRWAY HYPERREACTIVITY; ANTIINFLAMMATORY ROLE; OSTEOCLAST FORMATION; MEVALONATE PATHWAY AB The bisphosphonates are a novel class of drug that have been registered for various clinical applications worldwide. Bisphosphonates, and in particular the aminobisphosphonates (nBPs), are known to have a number of side-effects including a rise in body temperature and accompanying flu-like symptoms that resemble a typical acute phase response. The mechanism for this response has been partially elucidated and appears to be associated with the release of tumour necrosis factor (TNF)alpha and interleukin (IL)6, although the effector cells that release these cytokines and the mechanism of action remain enigmatic. Here, we show that the nBP-induced acute phase response differs from the typical acute phase response in that CD14(+) cells such as monocytes and macrophages are not the primary cytokine producing cells. We show that by inhibiting the mevalonate pathway, nBPs induce rapid and copious production of TNFalpha and IL6 by peripheral blood gammadelta T cells. Prior treatment with statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, blocks nBP-induced production of these proinflammatory cytokines by gammadelta T cells and may offer a means of avoiding the associated acute phase response. In addition, our findings provide a further mechanism for the anti-inflammatory effects attributed to inhibitors of HMG CoA reductase. C1 T Cell Modulat Grp, Oxford OX1 3SY, England. Univ S Australia, Sch Pharm & Med Sci, Adelaide, SA 5001, Australia. NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Sewell, AK (reprint author), T Cell Modulat Grp, Peter Medawar Bldg Pathogen Res,S Parks Rd, Oxford OX1 3SY, England. EM andy.sewell@ndm.ox.ac.uk RI Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Hewitt, Rachel/0000-0002-2367-1822 FU Medical Research Council [G108/441]; Multiple Sclerosis Society [589] NR 80 TC 128 Z9 131 U1 1 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JAN PY 2005 VL 139 IS 1 BP 101 EP 111 DI 10.1111/j.1365-2249.2005.02665.x PG 11 WC Immunology SC Immunology GA 879YF UT WOS:000225754600014 PM 15606619 ER PT J AU Lam, LT Davis, RE Pierce, J Hepperle, M Xu, YJ Hottelet, M Nong, YH Wen, DY Adams, J Dang, L Staudt, LM AF Lam, LT Davis, RE Pierce, J Hepperle, M Xu, YJ Hottelet, M Nong, YH Wen, DY Adams, J Dang, L Staudt, LM TI Small molecule inhibitors of I kappa B kinase are selectively toxic for subgroups of diffuse large B-cell lymphoma defined by gene expression profiling SO CLINICAL CANCER RESEARCH LA English DT Article ID HODGKIN/REED-STERNBERG CELLS; HUMAN MULTIPLE-MYELOMA; TRANSCRIPTION FACTORS; INDUCED APOPTOSIS; DRUG DEVELOPMENT; ACTIVATION; INDUCTION; CANCER; ALPHA; DISEASE AB Constitutive activation of the NF-kappaB pathway is required for survival of the activated B cell-like (ABC) subgroup of diffuse large B-cell lymphoma (DLBCL). Here we show that a small molecule IkappaB kinase (IKK) inhibitor, PS-1145, and related compounds are toxic for ABC DLBCL cell lines but not for cell lines derived from the other prevalent form of DLBCL, germinal center B cell-like DLBCL. Treatment of ABC lines with these inhibitors rapidly induced a series of gene expression changes that were attributable to cessation of constitutive IKK activity, similar to changes induced by acute expression of genetic inhibitors of NF-kappaB, confirming the effectiveness and specificity of this compound. Before cell death, inhibition of IKK also induced features of apoptosis and an arrest in the G, phase of the cell cycle. To test further the specificity of this toxicity, an inducible form of NF-kappaB was created by fusing the p65 NF-kappaB subunit with the ligand-binding domain of the estrogen receptor (p65-ERD). In the presence of tamoxifen, p65-ERD reversed the toxicity of IKK inhibition and restored expression of many NF-kappaB target genes. Another subgroup of DLBCL, primary mediastinal B-cell lymphoma (PMBL), also expresses NF-kappaB target genes, and treatment of a PMBL cell line with an IKK inhibitor was toxic and induced gene expression changes of a distinct group of NF-kappaB target genes. These studies validate the NF-kappaB pathway as a promising therapeutic target in ABC DLBCL, PMBL, and other lymphomas that depend on the activity of NF-kappaB for survival and proliferation. C1 NCI, NIH, Metab Branch, Canc Res Ctr, Bethesda, MD USA. Millenium Pharmaceut, Cambridge, MA USA. RP Staudt, LM (reprint author), 9000 Rockville Pike,Bldg 10,Room 5A-02, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov NR 49 TC 232 Z9 238 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2005 VL 11 IS 1 BP 28 EP 40 PG 13 WC Oncology SC Oncology GA 884TW UT WOS:000226110300006 PM 15671525 ER PT J AU Ise, T Maeda, H Santora, K Xiang, LM Kreitman, RJ Pastan, I Nagata, S AF Ise, T Maeda, H Santora, K Xiang, LM Kreitman, RJ Pastan, I Nagata, S TI Immunoglobulin superfamily receptor translocation associated 2 protein on lymphoma cell lines and hairy cell leukemia cells detected by novel monoclonal antibodies SO CLINICAL CANCER RESEARCH LA English DT Article ID FC RECEPTOR HOMOLOGS; NON-HODGKINS-LYMPHOMA; B-CELLS; RECOMBINANT IMMUNOTOXINS; PSEUDOMONAS EXOTOXIN; FAMILY; IDENTIFICATION; REARRANGEMENT; TRANSLOCATION; CHEMOTHERAPY AB Purpose: The immunoglobulin superfamily receptor translocation associated 2 (IRTA2) gene encodes a cell surface receptor homologous to the family of Fc receptors. Because of the restricted expression of mRNA in B cell-lineage cells, IRTA2 is a new potential target for the immunotherapy of B cell malignancies. To study the expression of the IRTA2 gene product, we produced monoclonal antibodies (MAbs) specific to IRTA2. Experimental Design: A mouse used for cell fusion was DNA-immunized with an expression plasmid encoding the IRTA2 cDNA. The reactivity of MAbs secreted from the hybridomas were characterized with recombinant proteins of IRTA family members in an enzyme immunoassay and a fluorescence-activated cell sorter (FACS). Nineteen human lymphoma cell lines and blood cells from five patients with hairy cell leukemia (HCL) were analyzed with IRTA2 expression using FACS. Results: Three MAbs (1725, F56, and F119) were selected based on their specific reactivity with recombinant IRTA2 and lack of cross-reactivity with other IRTA family members. In a FACS analysis, MAbs F56 and F119 detected IRTA2 expression in six of seven B cell non-Hodgkin's lymphoma and one of six Burkitt's lymphoma cell lines. Reverse transcriptase-PCR experiments and Western blotting using MAb F25 confirmed the expression profile. We also found that HCL cells from five patients expressed IRTA2. Conclusions: Our results provide the first evidence that IRTA2 is expressed on the surface of human lymphoma cell lines and HCL cells. IRTA2 could be useful as a new target for immunotherapy. C1 NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov NR 35 TC 24 Z9 26 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2005 VL 11 IS 1 BP 87 EP 96 PG 10 WC Oncology SC Oncology GA 884TW UT WOS:000226110300013 PM 15671532 ER PT J AU Wang, E Ngalame, Y Panelli, MC Nguyen-Jackson, H Deavers, M Mueller, P Hu, W Savary, CA Kobayashi, R Freedman, RS Marincola, FN AF Wang, E Ngalame, Y Panelli, MC Nguyen-Jackson, H Deavers, M Mueller, P Hu, W Savary, CA Kobayashi, R Freedman, RS Marincola, FN TI Peritoneal and subperitoneal stroma may facilitate regional spread of ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID MESSENGER-RNA AMPLIFICATION; GROWTH-FACTOR; MESOTHELIAL CELLS; CARCINOMA-CELLS; ASCITIC FLUID; TUMOR-CELLS; IN-VITRO; EXPRESSION PATTERNS; ADHESION; ACTIVATION AB Purpose: Epithelial ovarian cancer (EOC) is characterized by early peritoneal involvement ultimately contributing to morbidity and mortality. To study the role of the peritoneum in fostering tumor invasion, we analyzed differences between the transcriptional repertoires of peritoneal tissue lacking detectable cancer in patients with EOC versus benign gynecologic disease. Experimental Design: Specimens were collected at laparotomy from patients with benign disease (b) or malignant (m) ovarian pathology and comprised primary ovarian tumors, paired bilateral specimens from adjacent peritoneum and attached stroma (PE), subjacent stroma (ST), peritoneal washes, ascites, and peripheral blood mononuclear cells. Specimens were immediately frozen. RNA was amplified by in vitro transcription and cohybridized with reference RNA to a custom-made 17.5k cDNA microarray. Results: Principal component analysis and unsupervised clustering did not segregate specimens from patients with benign or malignant pathology. Class comparison identified differences between benign and malignant PE and ST specimens deemed significant by permutation test (P = 0.027 and 0.012, respectively). A two-tailed Student's t test identified 402 (bPE versus mPE) and 663 (mST versus bST) genes differentially expressed at a significance level of P-2 less than or equal to 0.005 when all available paired samples from each patient were analyzed. The same comparison using one sample per patient reduced the pool of differentially expressed genes but retained permutation test significance for bST versus mST (P = 0.031) and borderline significance for bPE versus mPE (P = 0.056) differences. Conclusions: The presence of EOC may foster peritoneal implantation and growth of cancer cells by inducing factors that may represent molecular targets for disease control. C1 NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA. RP Marincola, FN (reprint author), NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bldg 10,R-1C711, Bethesda, MD 20892 USA. EM Fmarincola@cc.nih.gov NR 56 TC 73 Z9 76 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2005 VL 11 IS 1 BP 113 EP 122 PG 10 WC Oncology SC Oncology GA 884TW UT WOS:000226110300016 PM 15671535 ER PT J AU Burke, L Flieder, DB Guinee, DG Brambilla, E Freedman, AN Bennett, WP Jones, RT Borkowski, A Caporaso, NA Fleming, M Trastek, V Pairolero, P Tazelaar, H Midthun, D Jett, JR Liotta, LA Travis, WD Harris, CC AF Burke, L Flieder, DB Guinee, DG Brambilla, E Freedman, AN Bennett, WP Jones, RT Borkowski, A Caporaso, NA Fleming, M Trastek, V Pairolero, P Tazelaar, H Midthun, D Jett, JR Liotta, LA Travis, WD Harris, CC TI Prognostic implications of molecular and immunohistochemical profiles of the Rb and p53 cell cycle regulatory pathways in primary non-small cell lung carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID RETINOBLASTOMA PROTEIN EXPRESSION; D1 OVEREXPRESSION; ALTERED RETINOBLASTOMA; DEPENDENT KINASES; NUCLEAR-PROTEIN; CANCER; GENE; INACTIVATION; P16(INK4A); GROWTH AB Purpose: Many studies have highlighted the aberrant expression and prognostic significance of individual proteins in either the Rb (particularly cyclin D1, p16(INK4A), and pRb) or the p53 (p53 and p21(Waf1)) pathways in non-small cell lung cancer. We hypothesize that cumulative abnormalities within each and between these pathways would have significant prognostic potential regarding survival. Experimental Design: Our study population consisted of 106 consecutive surgically resected cases of predominantly early-stage non-small cell lung cancer from the National Cancer Institute-Mayo Clinic series, and assessment of proteins involved both immunohistochemical (cyclin D1, p21(Waf1), pRb, p16(INK4A), and p53) and mutational analysis (p53) in relationship to staging and survival. Results: Cyclin D1 overexpression was noted in 48% of the tumors, p16(INK4A) negative in 53%, pRb negative in 17%, p53 immunopositive in 50%, p53 mutation frequency in 48%, and p21(Waf1) overexpression in 47%, none with prognostic significance. Cyclin D1 overexpression in pRb-negative tumors revealed a significantly worse prognosis with a mean survival of 2.3 years (P = 0.004). A simultaneous p53 mutation dramatically reduced the mean survival time to 0.9 years (P = 0.007). Cyclin D1 overexpression with either a p53 mutation or a p53 overexpression was also associated with a significantly poorer prognosis (P = 0.0033 and 0.0063, respectively). Conclusions: Some cumulative abnormalities in the Rb and p53 pathways (e.g., cyclin D1 overexpression and p53 mutations) significantly cooperate to predict a poor prognosis; however, the complexity of the cell cycle protein interaction in any given tumor warrants caution in interpreting survival results when specific protein abnormalities are taken in isolation. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Cork Univ Hosp, Dept Pathol, Cork, Ireland. Cornell Univ, New York Hosp, Coll Med, Dept Pathol, New York, NY USA. Virginia Mason Clin, Dept Pathol, Seattle, WA 98101 USA. CHU Grenoble, Serv Pathol Cellulaire, F-38043 Grenoble, France. Canc Surveillance Res Program, Appl Res Branch, Bethesda, MD USA. Genet Epidemiol Branch, Bethesda, MD USA. Pathol Lab, Bethesda, MD USA. City Hope Natl Med Ctr, Div Human Genet, Duarte, CA 91010 USA. City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. Mayo Clin Scottsdale, Dept Thorac Surg, Scottsdale, AZ USA. Mayo Clin, Dept Thorac Surg, Rochester, MN USA. Mayo Clin, Dept Pathol, Rochester, MN USA. Mayo Clin, Div Thorac Dis, Rochester, MN USA. Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Room 3068, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov RI Brambilla, Elisabeth/L-8796-2013 NR 69 TC 46 Z9 49 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2005 VL 11 IS 1 BP 232 EP 241 PG 10 WC Oncology SC Oncology GA 884TW UT WOS:000226110300032 PM 15671551 ER PT J AU Hortin, GL AF Hortin, GL TI Can mass spectrometric protein profiling meet desired standards of clinical laboratory practice? SO CLINICAL CHEMISTRY LA English DT Editorial Material ID PROTEOMIC PATTERNS; NEURAL NETWORKS; OVARIAN-CANCER; SERUM; DIAGNOSTICS C1 NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Bldg 10,Room 2C-407, Bethesda, MD 20892 USA. EM ghortin@mail.cc.nih.gov NR 15 TC 75 Z9 78 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2005 VL 51 IS 1 BP 3 EP 5 DI 10.1373/clinchem.2004.043281 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 883DS UT WOS:000225991100002 PM 15613702 ER PT J AU Semmes, OJ Feng, Z Adam, BL Banez, LL Bigbee, WL Campos, D Cazares, LH Chan, DW Grizzle, WE Izbicka, E Kagan, J Malik, G McLerran, D Moul, JW Partin, A Prasanna, P Rosenzweig, J Sokoll, LJ Srivastava, S Srivastava, S Thompson, I Welsh, MJ White, N Winget, M Yasui, Y Zhang, Z Zhu, L AF Semmes, OJ Feng, Z Adam, BL Banez, LL Bigbee, WL Campos, D Cazares, LH Chan, DW Grizzle, WE Izbicka, E Kagan, J Malik, G McLerran, D Moul, JW Partin, A Prasanna, P Rosenzweig, J Sokoll, LJ Srivastava, S Srivastava, S Thompson, I Welsh, MJ White, N Winget, M Yasui, Y Zhang, Z Zhu, L TI Evaluation of serum protein profiling by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry for the detection of prostate cancer: I. Assessment of platform reproducibility SO CLINICAL CHEMISTRY LA English DT Article ID PROTEOMIC PATTERNS; CELL CARCINOMA; BREAST-CANCER; NECK-CANCER; SELDI-TOF; IDENTIFICATION; BIOMARKERS; DIAGNOSIS; VALIDATION; DISCOVERY AB Background: Protein expression profiling for differences indicative of early cancer has promise for improving diagnostics. This report describes the first stage of a National Cancer Institute/Early Detection Research Network-sponsored multiinstitutional evaluation and validation of this approach for detection of prostate cancer. Methods: Two sequential experimental phases were conducted to establish interlaboratory calibration and standardization of the surf ace-enhanced laser desorption (SELDI) instrumental and assay platform output. We first established whether the output from multiple calibrated Protein Biosystem II SELDI-ionization time-of-flight mass spectrometry (TOF-MS) instruments demonstrated acceptable interlaboratory reproducibility. This was determined by measuring mass accuracy, resolution, signal-to-noise ratio, and normalized intensity of three m/z "peaks" present in a standard pooled serum sample. We next evaluated the ability of the calibrated and standardized instrumentation to accurately differentiate between selected cases of prostate cancer and control by use of an algorithm developed from data derived from a single site 2 years earlier. Results: When the described standard operating procedures were established at all laboratory sites, the across-laboratory measurements revealed a CV for mass accuracy of 0.1%. signal-to-noise ratio of similar to40%, and normalized intensity of 15-36% for the three pooled serum peaks. This was comparable to the intralaboratory measurements of the same peaks. The instrument systems were then challenged with sera from a selected group of 14 cases and 14 controls. The classification agreement between each site and the established decision algorithm were examined by use of both raw peak intensity boosting and ranked peak intensity boosting. All six sites achieved perfect blinded classification for all samples when boosted alignment of raw intensities was used. Four of six sites achieved perfect blinded classification with ranked intensities, with one site passing the criteria of 26 of 28 correct and one site failing with 19 of 28 correct. Conclusions: These results demonstrate that "between-laboratory" reproducibility of SELDI-TOF-MS serum profiling approaches that of "within-laboratory" reproducibility as determined by measuring discrete m/z peaks over time and Across laboratories. (C) 2005 American Association for Clinical Chemistry. C1 Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, Virginia Prostate Ctr, Norfolk, VA 23507 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Uniformed Serv Univ Hlth Sci, Ctr Prostate Dis Res, Dept Surg, Rockville, MD USA. Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA USA. Inst Drug Dev, Canc Therapy & Res Ctr, San Antonio, TX USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Natl Canc Inst, Div Canc Prevent, Canc Biomakers Res Grp, Bethesda, MD USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. RP Semmes, OJ (reprint author), Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, Virginia Prostate Ctr, 700 W Olney Rd, Norfolk, VA 23507 USA. EM semmesoj@evms.edu RI Yasui, Yutaka/E-2564-2015 OI Yasui, Yutaka/0000-0002-7717-8638 FU NCI NIH HHS [CA84968, CA85067, CA86323, CA86359, CA86368, CA86402, U01 CA085067, U01CA084986] NR 39 TC 260 Z9 290 U1 0 U2 7 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2005 VL 51 IS 1 BP 102 EP 112 DI 10.1373/clinchem.2004.038950 PG 11 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 883DS UT WOS:000225991100019 PM 15613711 ER PT J AU Gross, M Steffes, M Jacobs, DR Yu, XH Lewis, L Lewis, CE Loria, CM AF Gross, M Steffes, M Jacobs, DR Yu, XH Lewis, L Lewis, CE Loria, CM TI Plasma F-2-isoprostanes and coronary artery calcification: The CARDIA study SO CLINICAL CHEMISTRY LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; LIPID-PEROXIDATION; HEART-DISEASE; RISK-FACTORS; VITAMIN-E; ANTIOXIDANT VITAMINS; COMPUTED-TOMOGRAPHY; OXIDATIVE STRESS; CALCIUM; ATHEROSCLEROSIS AB Background: Oxidation of lipids in lipoproteins and cells may initiate and enhance the early development of cardiovascular disease. Method and Results: We assayed F-2-isoprostanes, oxidation products of arachidonic acid, by gas chromatography-mass spectrometry in a biracial cohort of 2850 young healthy adult men and women. Coronary artery calcification (CAC), a component of coronary artery atherosclerosis, was detectable in 10% of the cohort and appeared to be in its initial stages (Agatston scores <20 in 47% and <100 in 83% of CAC-positive participants). After adjusting for sex, clinical site, age, and race, the presence of any CAC was 24% more likely among those with high vs low concentrations of F-2-isoprostanes [odds ratio (OR) = 1.24 per 92.2 pmol/L (32.7 ng/L; 1 SD of F-2-isoprostanes); 95% confidence interval (CI), 1.09-1.41]. The OR was only slightly attenuated [1.18 per 92.2 pmol/L (32.7 ng/L); CI, 1.02-1.38] after further adjustment for body mass index, smoking, serum lipids, C-reactive protein, antioxidant supplementation use, diabetes, and blood pressure. As a continuous variable, the Agatston score increased by 6.9% per 92.2 pmol/L (32.7 ng/L) of F-2-isoprostane concentration (P <0.01). Whereas CAC prevalence was lower in women than men, mean (SD), F-2-isoprostanes were higher in women {190 (108.9) pmol/L [67.4 (38.6) ng/L]} than in men {140.4 (55.6) pmol/L [49.8 (19.7) ng/L]}. Nevertheless, F-2-isoprostartes were associated with an increased risk of CAC in both sexes. Conclusion: This association between increased concentrations of circulating F-2-isoprostanes and CAC in young healthy adults supports the hypothesis that oxidative damage is involved in the early development of atherosclerosis. (C) 2005 American Association for Clinical Chemistry. C1 Univ Minnesota, Sch Med, Dept Pathol & Lab Med, Minneapolis, MN 55455 USA. Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Oslo, Dept Nutr, Oslo, Norway. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. RP Gross, M (reprint author), Univ Minnesota, Sch Med, Dept Pathol & Lab Med, Mayo Mail Code 609,420 Delaware St SE, Minneapolis, MN 55455 USA. EM gross@epi.umn.edu RI Yu, Xinhua/D-5570-2009 FU NHLBI NIH HHS [1R011-HL53560-01A1, N01-HC-45134, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-95095] NR 40 TC 81 Z9 83 U1 0 U2 4 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2005 VL 51 IS 1 BP 125 EP 131 DI 10.1373/clinchem.2004.037630 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 883DS UT WOS:000225991100022 PM 15514100 ER PT J AU Chan, Y Bowen, RA Remaley, AT AF Chan, Y Bowen, RA Remaley, AT TI Investigation of immunoassay interference from reformulated blood collection tubes. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 24-28, 2005 CL Orlando, FL SP Amer Assoc Clin Chem C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PY 2005 VL 51 SU 6 BP A46 EP A46 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 930YH UT WOS:000229452500145 ER PT J AU Chan, YW Connors, SA Remaley, AT AF Chan, YW Connors, SA Remaley, AT TI Utility of monitoring serum calcium and ionized calcium during parathyroidectomy surgery SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 24-28, 2005 CL Orlando, FL SP Amer Assoc Clin Chem C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PY 2005 VL 51 SU 6 BP A233 EP A233 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 930YH UT WOS:000229452500751 ER PT J AU Eisenhofer, G Lenders, JW Goldstein, DS Mannelli, M Csako, G Walther, MM Brouwers, FM Pacak, K AF Eisenhofer, G Lenders, JW Goldstein, DS Mannelli, M Csako, G Walther, MM Brouwers, FM Pacak, K TI Pheochromocytoma catecholamine phenotypes and prediction of tumor size and location using plasma free metanephrines SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 24-28, 2005 CL Orlando, FL SP Amer Assoc Clin Chem C1 NIH, Bethesda, MD 20892 USA. St Radboud Hosp, Nijmegen, Netherlands. Univ Florence, Florence, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PY 2005 VL 51 SU 6 BP A62 EP A63 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 930YH UT WOS:000229452500199 ER PT J AU Sampson, ML Ruddel, ME Rehak, NN Remaley, AT AF Sampson, ML Ruddel, ME Rehak, NN Remaley, AT TI Real time monitoring of the analytical performance of clinical chemistry analyzers by moving window delta check analysis SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 24-28, 2005 CL Orlando, FL SP Amer Assoc Clin Chem C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PY 2005 VL 51 SU 6 BP A216 EP A216 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 930YH UT WOS:000229452500699 ER PT J AU Sullivan, P Eisenhofer, G Csako, G AF Sullivan, P Eisenhofer, G Csako, G TI Comparison of heparin and EDTA plasma for the measurement of catecholamines and free metanephrines. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 24-28, 2005 CL Orlando, FL SP Amer Assoc Clin Chem C1 NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PY 2005 VL 51 SU 6 BP A49 EP A49 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 930YH UT WOS:000229452500154 ER PT J AU Dube, MP Kitch, DW Parker, RA Alston-Smith, BL Mulligan, K AF Dube, MP Kitch, DW Parker, RA Alston-Smith, BL Mulligan, K CA AIDS Clinical Trials Grp A5099 TI The effect of long-term storage on measured plasma lactate concentrations and prospective lactate results from a multicenter trial of antiretroviral therapy SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Article DE antiretroviral therapy; frozen storage; lactate measurement; lactic academia; nucleoside reverse transcriptase inhibitors ID VIRUS-INFECTED PATIENTS; SEQUENTIAL 3-DRUG REGIMENS; LACTIC-ACIDOSIS; UNINFECTED INFANTS; TREATED PATIENTS; NATURAL-HISTORY; HIV-1 INFECTION; INITIAL THERAPY; RISK-FACTORS; HYPERLACTATEMIA AB Plasma lactate measurements are typically performed in real time, limiting their usefulness in multicenter or longitudinal studies. To determine the stability of lactate specimens, blood was drawn in sodium fluoride/ potassium oxalate tubes from 13 volunteers before and after 5 min of handgrip exercise to intentionally increase lactate concentrations. Plasma was stored at -70 degrees C. Aliquots were assayed in real time and after 1, 3, 6, 9, 12, 18, and 24 months. Real-time lactate concentrations measured at baseline ranged from 0.52 to 2.23 mmol/L before and from 2.91 to 11.04 mmol/L after handgrip exercise. Using a linear mixed model, the estimated change from baseline at month 24 was 1.67% (95% confidence interval, -0.70% to 4.03%) for pre-exercise samples and 0.39% (95% Cl, -1.13% to 1.91%) for post-exercise samples. Stored serial specimens from 232 HIV-infected subjects in a multicenter trial of antiretroviral therapy were also assayed centrally. Among those, median plasma lactate increased from baseline to 64 weeks by 0.4 mmol/L with zidovudine+lamivudine treatment and by 0.6 mmol/L with didanosine+stavudine (each p<0.001 from baseline; p=0.04 for difference between groups over time). When performed as in this study, frozen storage with central batch lactate analysis is appropriate for prospectively collected samples in multicenter trials. C1 Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46204 USA. Indiana Univ, Sch Med, Div Infect Dis, Indianapolis, IN 46204 USA. Harvard Univ, Sch Publ Hlth, Stat Data Anal Ctr, Boston, MA 02115 USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. San Francisco Gen Hosp, Div Endocrinol, San Francisco, CA 94110 USA. RP Dube, MP (reprint author), Wishard Mem Hosp, 1001 W 10th St,Suite OPW 430, Indianapolis, IN 46202 USA. EM mpdube@iupui.edu FU NCRR NIH HHS [RR 00083, RR 00750]; NIAID NIH HHS [AI 25859, AI 38858, AI 38855, AI 27663] NR 26 TC 7 Z9 7 U1 0 U2 0 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PY 2005 VL 43 IS 9 BP 947 EP 952 DI 10.1515/CCLM.2005.162 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 970VH UT WOS:000232340000011 PM 16176175 ER PT J AU Borowsky, AD Namba, R Young, LJT Hunter, KW Hodgson, JG Tepper, CG McGoldrick, ET Muller, WJ Cardiff, R Gregg, JP AF Borowsky, AD Namba, R Young, LJT Hunter, KW Hodgson, JG Tepper, CG McGoldrick, ET Muller, WJ Cardiff, R Gregg, JP TI Syngeneic mouse mammary carcinoma cell lines: Two closely related cell lines with divergent metastatic behavior SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE Akt; breast; breast carcinoma; cell line metastasis; comparative genomic hybridization; ERBB2; gene expression analysis; LY294002; mammary fat pad; mouse mammary tumor virus long terminal repeat; oncogene; orthotopic; phosphatidylinositol 3 kinase; polyoma middle T; pulmonary metastasis; Sept9; Spp1 osteopontin; Opn; syngeneic; transgenic; tumor transplant ID MIDDLE-T-ONCOGENE; BREAST-CANCER; TRANSGENIC MICE; IN-VIVO; MODEL; TUMOR; EXPRESSION; TUMORIGENESIS; INHIBITOR; DISEASE AB Two cell lines, Met-1(fvb2) and DB-7(fvb2), with different metastatic potential, were derived from mammary carcinomas in FVB/N-Tg(MMTV-PyVmT) and FVB/N-Tg(MMTV-PyVmT(Y315F/Y322F)) mice, transplanted into syngeneic FVB/N hosts and characterized. The lines maintain a stable morphological and biological phenotype after multiple rounds of in vitro culture and in vivo transplantation. The Met-1(fvb2) line derived from a FVB/N-Tg(MMTV-PyVmT) tumor exhibits invasive growth and 100% metastases when transplanted into the females FVB/N mammary fat pad. The DB-7(fvb2) line derived from the FVB/N-Tg(MMTV-PyVmT(Y315F/Y322F)) with a "double base" modification at Y315F/Y322F exhibits more rapid growth when transplanted into the mammary fat pad, but a lower rate of metastasis (17%). The Met1(fvb2) cells show high activation of AKT, while DB-7(fvb2) cells show very low levels of AKT activation. The DNA content and gene expression levels of both cell lines are stable over multiple generations. Therefore, these two cell lines provide a stable, reproducible resource for the study of metastasis modulators, AKT molecular pathway interactions, and gene target and marker discovery. C1 Univ Calif Davis, Dept Comparat Med, Ctr Comparat Med, Davis, CA 95616 USA. Univ Calif Davis, Sch Med, Dept Med Pathol & Lab Med, Sacramento, CA 95817 USA. NCI, Lab Populat Genet, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Univ Calif Davis, Sch Med, Dept Biochem & Mol Med, Sacramento, CA 95817 USA. McGill Univ, Royal Victoria Hosp, Mol Oncol Grp, Montreal, PQ H3A 1A1, Canada. RP Borowsky, AD (reprint author), Univ Calif Davis, Dept Comparat Med, Ctr Comparat Med, Hutchison & Cty Rd 98, Davis, CA 95616 USA. EM adborowsky@ucdavis.edu FU NCI NIH HHS [R01 CA 81736, P30 CA 93373-01] NR 37 TC 78 Z9 78 U1 2 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD JAN PY 2005 VL 22 IS 1 BP 47 EP 58 DI 10.1007/s10585-005-2908-5 PG 12 WC Oncology SC Oncology GA 947MT UT WOS:000230651000006 PM 16132578 ER PT J AU Azzam, A Lemer, DM Peters, KF Wiggs, E Rosenstein, C Biesecker, LG AF Azzam, A Lemer, DM Peters, KF Wiggs, E Rosenstein, C Biesecker, LG TI Psychiatric and neuropsychological characterization of Pallister-Hall syndrome SO CLINICAL GENETICS LA English DT Article DE ethics; genetic counselling; psychiatric disorder; psychological testing; single-gene disorders ID CONGENITAL HYPOTHALAMIC HAMARTOBLASTOMA; NATIONAL COMORBIDITY SURVEY; SUBSTANCE USE DISORDERS; DSM-III-R; ASCERTAINMENT BIAS; EPIDEMIOLOGY; HAMARTOMA; DEPRESSION; POPULATION; PHENOTYPES AB Pallister-Hall syndrome (PHS) is a rare single-gene malformation,. hypothalamic hamartoma. syndrome that includes central polydactyly., bifid epiglottis, endocrine dysfunction, and other anomalies. The syndrome has variable clinical manifestations and is inherited in an autosomal dominant pattern. We sought to determine whether psychiatric disorders and/or neuropsychological impairment were characteristic of PHS. We prospectively conducted systematic neuropsychiatric evaluations with 19 PHS subjects ranging in age from 7 to 75 years. The evaluation included detailed clinical interviews, clinician-rated and self-report instruments, and a battery of neuropsychological tests. Seven of 14 adult PHS subjects met diagnostic criteria for at least one DSM-IV Axis I disorder. Three additional subjects demonstrated developmental delays and/or neuropsychological deficits on formal neuropsychological testing. However, we found no characteristic psychiatric phenotype associated with PHS.. and the frequency of each of the diagnoses observed in these subjects was not different from that expected in this size sample. The overall frequency of psychiatric findings among all patients with PHS cannot be compared to point prevalence estimates of psychiatric disease in the general population because of biased ascertainment. This limitation is inherent to the study of behavioral phenotypes in rare disorders. The general issue of psychiatric evaluation of rare genetic syndromes is discussed in light of this negative result. C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. NIMH, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Azzam, A (reprint author), Univ Calif San Francisco, Dept Psychiat, POB 0984 RTP,401 Pamassus Ave, San Francisco, CA 94143 USA. EM azzama@fisa.ucsf.edu OI Azzam, Amin/0000-0002-7024-7450 NR 50 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JAN PY 2005 VL 67 IS 1 BP 87 EP 92 DI 10.1111/j.1399-004.2004.00370.x PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 892QN UT WOS:000226665200014 PM 15617553 ER PT J AU Raygada, M Rennert, O AF Raygada, M Rennert, O TI Congenital generalized lipodystrophy: profile of the disease and gender differences in two siblings SO CLINICAL GENETICS LA English DT Article DE acanthosis nigricans; acromegaloid features; adiposity; diabetes; hepatomegaly; insulin resistance ID GENE AB Congenital generalized Lipodystrophy (BSCL) or Berardinelli-Seip syndrome (Mendelian inheritance in man, catalog no. 269700) is a rare autosomal recessive syndrome characterized by paucity of body fat since birth and insulin resistance. The pathophysiology of this condition is unclear, but defects in insulin function and impaired adipogenesis have been described as important factors in the etiology of the disease. Recently, two gene loci have been identified to harbor the mutations causing this disorder: BSCL1 mapped to human chromosome 9q34 (1, 2) and BSCL2 mapped to human chromosome 11q13 (1 3). This report, describes the natural history of the disease in two siblings (female and male) of Lebanese origin who have mutations in the BSCL2 locus (669delGTATC). C1 Natl Inst Child Hlth & Human Dev, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. RP Raygada, M (reprint author), Natl Inst Child Hlth & Human Dev, Lab Clin Genom, NIH, Bldg 49,Room 2A03,49 Convent Dr MSC 4429, Bethesda, MD 20892 USA. EM mr346j@nih.gov NR 9 TC 1 Z9 2 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JAN PY 2005 VL 67 IS 1 BP 98 EP 101 DI 10.1111/j.1399-004.2004.00372.x PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 892QN UT WOS:000226665200016 PM 15617555 ER PT J AU Adriani, M Garbi, C Amodio, G Busiello, R Ferri, P Matrecano, E Candotti, F Pignata, C AF Adriani, M Garbi, C Amodio, G Busiello, R Ferri, P Matrecano, E Candotti, F Pignata, C TI Functional interaction of common gamma chain and growth hormone receptor signaling apparatus. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Univ Naples, Dept Pediat, I-80138 Naples, Italy. Univ Naples, Dept Cell & Mol Biol, I-80138 Naples, Italy. Univ Naples, Dept Pathol, I-80138 Naples, Italy. Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD USA. RI Adriani, Marsilio/F-2553-2013; Pignata, Claudio/O-2466-2013 OI Pignata, Claudio/0000-0003-1568-9843 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S29 EP S29 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400076 ER PT J AU Aoki, J Konno, A Jankovic, D Cannons, J Candotti, F Schwartzberg, P AF Aoki, J Konno, A Jankovic, D Cannons, J Candotti, F Schwartzberg, P TI The role of Wiskott Aldrich syndrome protein in T helper cell function. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Natl Human Genome Res Inst, Genet Dis Res Branch, Bethesda, MD USA. Natl Human Genome Res Inst, Genet & Mol Biol Branch, Bethesda, MD USA. NIAID, Lab Parasit Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S249 EP S249 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400699 ER PT J AU Chen, WJ Liu, Y AF Chen, WJ Liu, Y TI TGF-beta in Foxp3 expression and development of peripheral CD4+CD25+ Treg. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 NIDCR, OIIB, Mucosal Immunol Unit, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S205 EP S205 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400581 ER PT J AU Cortes, LM Avichezer, D Silver, PB Chan, CC Caspi, RR AF Cortes, LM Avichezer, D Silver, PB Chan, CC Caspi, RR TI Altered peptide ligands of a retinal antigen protect from anti-retinal autoimmunity by eliciting active regulatory mechanisms. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 NEI, NIH, Immunol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S139 EP S140 PG 2 WC Immunology SC Immunology GA 926DY UT WOS:000229104400390 ER PT J AU Germain, RN Huang, AY Qi, H Chieppa, M Egen, J Castellino, F Ifrim, I Scheinecker, C Eichelberg, K Wang, Z Stoll, S AF Germain, RN Huang, AY Qi, H Chieppa, M Egen, J Castellino, F Ifrim, I Scheinecker, C Eichelberg, K Wang, Z Stoll, S TI High resolution dynamic visualization of immune cell function in vivo in health and disease. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S41 EP S41 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400109 ER PT J AU Grajewski, RS Silver, PB Agarwal, RK Su, SB Chan, CC Liou, GI Caspi, RR AF Grajewski, RS Silver, PB Agarwal, RK Su, SB Chan, CC Liou, GI Caspi, RR TI Endogenous expression of IRBP is dispensable for generation of CD4+CD25+ regulatory T cells that protect against IRBP-induced retinal autoimmunity. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Med Coll Georgia, Augusta, GA 30912 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S216 EP S216 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400611 ER PT J AU Hill, TM Van Kaer, L Yewdell, JW Roopenian, DC Joyce, S AF Hill, TM Van Kaer, L Yewdell, JW Roopenian, DC Joyce, S TI Cross-presentation of minor histocompatibility antigens requires dendritic cells and immunoproteasomes. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S62 EP S62 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400171 ER PT J AU Korn, T Magnus, T Jung, S AF Korn, T Magnus, T Jung, S TI Autoantigen specific T cells inhibit glutamate uptake in astrocytes by decreasing expression of astrocytic glutamate transporter GLAST - A mechanism mediated by tumor necrosis factor-alpha. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Univ Saarland, Dept Neurol, D-66421 Homburg, Germany. NIA, Stem Cell Sect, Neurosci Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S91 EP S91 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400253 ER PT J AU Kump, LI Castaneda, RAC Androudi, SN Reed, GF Foster, CS AF Kump, LI Castaneda, RAC Androudi, SN Reed, GF Foster, CS TI Visual outcomes in children with juvenile idiopathic arthritis-associated uveitis. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S186 EP S186 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400526 ER PT J AU Kump, LI Moeller, KL Kurup, S Reed, GF Nussenblatt, RB AF Kump, LI Moeller, KL Kurup, S Reed, GF Nussenblatt, RB TI Adamantiades-Behcet's disease: A trend in time. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S185 EP S186 PG 2 WC Immunology SC Immunology GA 926DY UT WOS:000229104400525 ER PT J AU Lathey, JL Martinez, K Gregory, S D'Souza, P Lopaczynski, W AF Lathey, JL Martinez, K Gregory, S D'Souza, P Lopaczynski, W TI Characterization of assay variability in real-time and batch assays of sequential samples from the same donors. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 SeraCare Life Sci, BBI Biotech, Gaithersburg, MD USA. NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S266 EP S267 PG 2 WC Immunology SC Immunology GA 926DY UT WOS:000229104400752 ER PT J AU Li, ZQ Lim, WK Mahesh, SP Nussenblatt, RB AF Li, ZQ Lim, WK Mahesh, SP Nussenblatt, RB TI In vivo blockade of human IL-2 receptor (IL-2R) induces expansion of CD56(bright) regulatory NK cells in patients with active uveitis. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Singapore Natl Eye Ctr, Singapore, Singapore. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S213 EP S213 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400602 ER PT J AU Mikita, CP Holland, SM Nelson, MR AF Mikita, CP Holland, SM Nelson, MR TI An 8 year old girl with recurrent dermatomal herpes outbreaks SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Walter Reed Army Med Ctr, Dept Allergy Immunol, Washington, DC 20307 USA. NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S151 EP S152 PG 2 WC Immunology SC Immunology GA 926DY UT WOS:000229104400427 ER PT J AU Paganelli, R Di Iorio, A Ferracci, L Sparvieri, E Michetti, A Franceschi, C Cherubini, A Senin, U Abate, G AF Paganelli, R Di Iorio, A Ferracci, L Sparvieri, E Michetti, A Franceschi, C Cherubini, A Senin, U Abate, G TI Markers of inflammation, vitamin E and peripheral nervous system function. The InCHIANTI study. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Univ G DAnnunzio, Dept Med & Sci Aging, Chieti, Italy. NIH, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD USA. Univ Perugia, Inst Gerontol & Geriatr, I-06100 Perugia, Italy. Univ Bologna, Dept Biomed Sci, I-40126 Bologna, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S193 EP S193 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400546 ER PT J AU Salzer, U Chapel, HM Webster, ADB Pan-Hammarstrom, Q Peter, HH Schmitt-Graff, A Rockstroh, JK Schaffer, AA Hammarstrom, L Grimbacher, B AF Salzer, U Chapel, HM Webster, ADB Pan-Hammarstrom, Q Peter, HH Schmitt-Graff, A Rockstroh, JK Schaffer, AA Hammarstrom, L Grimbacher, B TI Mutations in TACI are associated with immunodeficient phenotypes in humans. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 Univ Freiburg, Inst Pathol, D-7800 Freiburg, Germany. Oxford Radcliffe Hosp, Dept Immunol, Oxford, England. Royal Free Hosp, Dept Clin Immunol, London NW3 2QG, England. Karolinska Inst, Div Clin Immunol, Huddinge, Sweden. Univ Bonn, Med Univ Klin 1, D-5300 Bonn, Germany. Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA. RI Schaffer, Alejandro/F-2902-2012 NR 0 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S29 EP S30 PG 2 WC Immunology SC Immunology GA 926DY UT WOS:000229104400078 ER PT J AU Shen, J Snyder, JT Azmi, H Ragheb, JA AF Shen, J Snyder, JT Azmi, H Ragheb, JA TI Anti-IL-2R therapy: An alternative strategy for regulating CD40L expression. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S38 EP S38 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400102 ER PT J AU Tang, J Zhu, W Sliver, PB Shu, SB Chan, CC Caspi, RR AF Tang, J Zhu, W Sliver, PB Shu, SB Chan, CC Caspi, RR TI Fit3L-elicited, in vitro-matured splenic dendritic cells (DC) induce autoimmune disease in the retina. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 NEI, Sect Immunoregulat, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S139 EP S139 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400388 ER PT J AU Uzel, G Malech, HL Holland, SM AF Uzel, G Malech, HL Holland, SM TI Atypical Mycobacterial infection and chronic granulomatous disease: Experience of one center. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NIAID, Lab Host Def, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S251 EP S252 PG 2 WC Immunology SC Immunology GA 926DY UT WOS:000229104400706 ER PT J AU Robbins, JB Schneerson, R Gotschlich, EC AF Robbins, JB Schneerson, R Gotschlich, EC TI Surveillance for bacterial meningitis by means of polymerase chain reaction SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material C1 NICHHD, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, New York, NY 10021 USA. RP Robbins, JB (reprint author), NICHHD, NIH, Bldg 31,Rm 2A29, Bethesda, MD 20892 USA. EM robbinsjo@mail.nih.gov NR 8 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2005 VL 40 IS 1 BP 26 EP 27 DI 10.1086/426448 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904JK UT WOS:000227492300005 PM 15614688 ER PT J AU Francis, JS Doherty, MC Lopatin, U Johnston, CP Sinha, G Ross, T Cai, M Hansel, NN Perl, T Ticehurst, JR Carroll, K Thomas, DL Nuermberger, E Bartlett, JG AF Francis, JS Doherty, MC Lopatin, U Johnston, CP Sinha, G Ross, T Cai, M Hansel, NN Perl, T Ticehurst, JR Carroll, K Thomas, DL Nuermberger, E Bartlett, JG TI Severe community-onset pneumonia in healthy adults caused by methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine leukocidin genes SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID FIELD GEL-ELECTROPHORESIS; ACQUIRED MRSA; UNITED-STATES; RISK-FACTORS; INFECTIONS; STRAINS; IDENTIFICATION; PREVALENCE; HOSPITALS; EMERGENCE AB Background. Recent worldwide reports of community- onset skin abscesses, outbreaks of furunculosis, and severe pneumonia associated with methicillin- resistant Staphylococcus aureus ( MRSA) carrying Panton- Valentine leukocidin ( PVL) genes and the staphylococcal cassette chromosome mec ( SCCmec) type IV indicate that MRSA infections are evolving into a community- related problem. The majority of cases reported to date involve skin and soft- tissue infections, with severe pneumonia representing a relatively rare phenomenon. During a 2- month period in the winter of 2003 - 2004, four healthy adults presented to 1 of 2 Baltimore hospitals with severe necrotizing MRSA pneumonia in the absence of typical risk factors for MRSA infection. Methods. Patients' MRSA isolates were characterized by strain typing with use of pulsed- field gel electrophoresis and SCCmec typing with use of a multiplex polymerase chain reaction ( PCR) assay and detection of PVL genes by PCR. Results. All 4 patients' MRSA isolates carried the PVL genes and the SCCmec type IV element and belonged to the USA300 pulsed- field type. These 3 findings are among the typical characteristics of community- onset MRSA strains. In addition, 2 of our patients had concomitant influenza A diagnosed, which likely contributed to the severity of their presentation. Conclusions. To our knowledge, these patients represent the first reported North American adults with severe community- onset MRSA pneumonia caused by strains carrying the PVL genes. C1 Johns Hopkins Univ, Div Infect Dis, Dept Med, Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Div Pulm & Crit Care Med, Dept Med, Baltimore, MD USA. Johns Hopkins Med Inst, Div Med Microbiol, Dept Pathol, Baltimore, MD USA. NIAID, NIH, Bethesda, MD USA. RP Francis, JS (reprint author), Johns Hopkins Univ, Div Infect Dis, Dept Med, Johns Hopkins Med Inst, 1830 E Monument St,Ste 401, Baltimore, MD 21205 USA. EM jfranc13@jhmi.edu RI Ticehurst, John/I-7532-2012 NR 35 TC 469 Z9 485 U1 2 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2005 VL 40 IS 1 BP 100 EP 107 DI 10.1086/427148 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904JK UT WOS:000227492300015 PM 15614698 ER PT J AU Hosey, LA Thompson, JLW Metman, LV van den Munckhof, P Braun, AR AF Hosey, LA Thompson, JLW Metman, LV van den Munckhof, P Braun, AR TI Temporal dynamics of cortical and subcortical responses to apomorphine in Parkinson disease - An (H2OPET)-O-15 study SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE apomorphine; Parkinson disease; dopamine agonists; pharmacodynamics ID POSITRON-EMISSION-TOMOGRAPHY; SUPPLEMENTARY MOTOR AREA; CEREBRAL BLOOD-FLOW; GLUCOSE-METABOLISM; BASAL GANGLIA; LEVODOPA; MOVEMENT; CORTEX; PET; SPECIFICITY AB (H2O)-O-15 positron emission tomography (PET) was used to study the temporal course of central nervous system (CNS) responses to apomorphine in patients with idiopathic Parkinson disease (PD). Agonist-induced changes in regional cerebral blood flow (rCBF) were evaluated within corticostriatal-thalamocortical circuits as well as in regions that extend beyond the standard pathophysiological model for PD. Compared with controls, rCBF was increased in PD patients in subcortical regions including the basal ganglia and cerebellum and both increased and decreased in prefrontal, parietal, sensorimotor, and paralimbic cortical areas. Apomorphine reversed many of these effects and had widespread effects throughout the brain. We evaluated the effects of apomorphine as they changed over time, comparing rCBF before the motor response and at later times when the motor response was maximal. Apomorphine's effects on functional connectivity also changed over time; activity in the ventrolateral thalamus was coupled with that in the SMA and cerebellum at the time of maximum motor response, but not at 45 seconds. Apomorphine affected rCBF in regions commonly considered part of the pathophysiological model of PD (eg, basal ganglia, thalamus, SMA), and other effects were seen in regions outside of the model (eg, cerebellum and superior parietal lobule). Results are discussed in light of this model. C1 NIDOCDS, NIH, Language Sect, Voice Speech & Language Branch, Bethesda, MD 20892 USA. Rush Univ, Ctr Med, Dept Neurol Sci, Chicago, IL 60612 USA. Univ Amsterdam, Dept Neurosurg, Amsterdam, Netherlands. RP Braun, AR (reprint author), NIDOCDS, NIH, Language Sect, Voice Speech & Language Branch, Bldg 10,Room 5N118A, Bethesda, MD 20892 USA. EM brauna@nidcd.nih.gov NR 43 TC 10 Z9 10 U1 1 U2 2 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 2005 VL 28 IS 1 BP 18 EP 27 DI 10.1097/01.wnf.0000154220.30263.0e PG 10 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 898NA UT WOS:000227082300005 PM 15711435 ER PT J AU Onda, M Bruland, OS Pastan, I AF Onda, M Bruland, OS Pastan, I TI TP-3 immunotoxins improve antitumor activity in mice with osteosarcoma SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID DISULFIDE-STABILIZED FV; NONSPECIFIC ANIMAL TOXICITY; GRADE CENTRAL OSTEOSARCOMA; IMPROVED ANTIGEN-BINDING; RECOMBINANT IMMUNOTOXINS; NEOADJUVANT CHEMOTHERAPY; IMMUNOGLOBULIN FORMS; ANTIBODY FRAGMENTS; ISOELECTRIC POINT; FRAMEWORK REGIONS AB We measured the antitumor activity of two types of TP-3 immunotoxins that target an antigen expressed in tumors associated with osteosarcoma. Development of novel agents for treatment of patients with osteosarcoma is important. We previously described a monovalent-disulfide-stabilized recombinant immunotoxin made from the TP-3 antibody. This agent is called TP-3(dsFv)-PE38 and is cytotoxic to human osteosarcoma cells in vitro. To improve antigen binding, we designed and produced a bivalent immunotoxin, TP3(dsFv)(2)-PE38. We evaluated the activity of both molecules in vitro and in vivo using tumor-bearing mice. Compared with the monovalent TP-3 immunotoxin, the bivalent TP-3 immunotoxin showed an approximately sevenfold increase in cytotoxic activity against three osteosarcoma cell lines which react with the TP-3 monoclonal antibody. The apparent affinity of the bivalent TP-3 immunotoxin was 12-fold greater than that of the monovalent TP-3 immunotoxin. The antitumor activities of both TP-3 immunotoxins were measured using severe combined immunodeficient mice bearing osteosarcoma cell line OHS-M1 tumors. The dose at which the bivalent TP-3 immunotoxin produces complete regressions of tumors is 1/2 that of the monovalent TP-3 immunotoxin. Increasing the avidity of TP-3(dsFv)-PE38 significantly improves its cytotoxic activity in vitro and results in a twofold increase in antitumor activity in vivo. Because TP-3-based immunotoxins have good antitumor activity in mice, these molecules merit additional development for possible treatment of osteosarcoma in humans. C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Dept Orthopaed Surg, Tokyo, Japan. Norwegian Radium Hosp, Dept Oncol, Oslo, Norway. RP Onda, M (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5110, Bethesda, MD 20892 USA. EM ondam@pop.nci.nih.gov NR 37 TC 5 Z9 6 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2005 IS 430 BP 142 EP 148 DI 10.1097/01.blo.0000137544.30200.b6 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 885GQ UT WOS:000226145500019 PM 15662316 ER PT J AU Smith, PF DiCenzo, R Forrest, A Shelton, M Friedland, G Para, M Pollard, R Fischl, M DiFrancesco, R Morse, GD AF Smith, PF DiCenzo, R Forrest, A Shelton, M Friedland, G Para, M Pollard, R Fischl, M DiFrancesco, R Morse, GD TI Population pharmacokinetics of delavirdine and N-delavirdine in HIV-infected individuals SO CLINICAL PHARMACOKINETICS LA English DT Review ID DIDANOSINE; INDINAVIR; MESYLATE; AGENTS; ADULTS; MODEL AB Objective: Delavirdine is a non-nucleoside reverse transcriptase inhibitor used in combination regimens for the treatment of HIV-1 infection. Our objective was to characterise the population pharmacokinetics of delavirdine in HIV-infected patients who participated in the adult AIDS Clinical Trials Group (ACTG) 260 and 261 studies. Methods: ACTG 261 was a randomised, double-blind study of delavirdine 400 mg three times daily, in various combination regimens; ACTG 260 was a concentration-targeted monotherapy study. Two hundred and thirty-four patients, and 1254 and 1251 plasma concentrations for delavirdine and N-delavirdine, respectively, were available for population pharmacokinetic analysis. The pharmacokinetic model (and initial parameters), based on previous studies, included two compartments for delavirdine (peripheral and central) and parallel clearance pathways (nonlinear conversion to N-delavirdine and first order clearance from the body). The model was one compartment for N-delaviridine with first order clearance. Diurnal variation of delavirdine and N-delavirdine oral clearance was modelled as a cosine functions with amplitude variation a fitted parameter. Pharmacokinetic parameter estimates were derived from iterative two-stage analysis; observed delavirdine and N-delavirdine concentrations fit with weighting by the inverse observation variance. Covariates were analysed by multiple general linear modelling. Results: The mean (percent coefficient of variation [%CV]) CD4 count was 315 (109) cells/mm(3), weight 76.9 (14.7) kg, age 37 (8.5) years, and 15% of the population were women. Mean (%CV) population pharmacokinetic parameter estimates for delavirdine were: volume of distribution at steady state 67.6 (100) L, intrinsic oral clearance 19.8 (64) L/h, concentration at half the maximum velocity. of metabolism (V-max) 6.3 (69) mumol/L and first order oral clearance 0.57 (86) L/h. For N-delavirdine, the mean (%CV) apparent volume of distribution was 24.7 (75) L and apparent clearance 29.7 (42) L/h. The mean Vmax was 1376 (68) mg/day. The final model for average intrinsic clearance of delavirdine included race, sex, weight and age as significant covariates (p < 0.05); however, these covariates do not explain a significant proportion of the overall variability in the population. Conclusions: Delavirdine disposition exhibits nonlinear pharmacokinetics and large interpatient variability, and is significantly altered by time of day (impacting potential therapeutic drug monitoring and future pharmacokinetic study designs). Although race and sex appear to influence delavirdine pharmacokinetics, men and women and patients of different races should receive similar mg/kg dosage regimens, The presence of large interpatient variability supports the further investigation of the utility of therapeutic drug monitoring for delavirdine, if target drug concentrations can be better defined. C1 SUNY Buffalo, Dept Pharm Practice, Sch Pharm & Pharmaceut Sci, Pharmacol Support Lab, Buffalo, NY 14260 USA. NIAID, Adult ACTG 260 & 261 Protocol Teams, Adult AIDS Clin Trials Grp, NIH, Bethesda, MD 20892 USA. Univ Miami, Dept Med, AIDS Clin Res Unit, Miami, FL 33152 USA. RP Smith, PF (reprint author), SUNY Buffalo, Dept Pharm Practice, Sch Pharm & Pharmaceut Sci, Pharmacol Support Lab, 219 Cooke Hall, Buffalo, NY 14260 USA. EM pfsmith@buffalo.edu NR 18 TC 6 Z9 6 U1 0 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PY 2005 VL 44 IS 1 BP 99 EP 109 DI 10.2165/00003088-200544010-00004 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 888HV UT WOS:000226365700004 PM 15634033 ER PT J AU Donovan, JL DeVane, CL Malcolm, RJ Mojsiak, J Chiang, CN Elkashef, A Taylor, RM AF Donovan, JL DeVane, CL Malcolm, RJ Mojsiak, J Chiang, CN Elkashef, A Taylor, RM TI Modafinil influences the pharmacokinetics of intravenous cocaine in healthy cocaine-dependent volunteers SO CLINICAL PHARMACOKINETICS LA English DT Review ID LIQUID-CHROMATOGRAPHY; DRUG; METABOLISM; EXPRESSION; ABUSERS AB Objective: To determine if modafinil, a putative treatment for cocaine dependence, influences the pharmacokinetics of intravenous cocaine in otherwise healthy cocaine-dependent volunteers. Methods: Cocaine 20 or 40mg was administered intravenously on consecutive days over 1 minute at baseline and after modafinil administration at each of two dosages of 400 and 800 mg/day for 7 days. Results: Twelve subjects completed the clinical protocol. Compared with baseline, the cocaine peak plasma concentration was decreased after both the 20 and 40mg cocaine infusions, but the reduction was only statistically significant after the 40mg cocaine infusion (p < 0.01 after modafinil 400 mg/day; p < 0.05 after modafinil 800 mg/day). The area under the cocaine plasma concentration-time curve from 0 to 180 minutes (AUC(180)) was significantly decreased by modafinil administration (p < 0.01 and p < 0.001 for modafinil 400 and 800 mg/day, respectively, for the cocaine 20mg dose; p < 0.001 for the cocaine 40mg dose at both modafinil levels). There were no significant changes in total AUC, clearance or elimination half-life of cocaine. Conclusion: This study did not find evidence for a harmful pharmacokinetic interaction between modafinil and cocaine. In contrast, long-term administration of modafinil significantly decreased systemic exposure to cocaine during the first 180 minutes following intravenous cocaine administration. C1 Med Univ S Carolina, Lab Drug Disposit & Pharmacogenet, Dept Psychiat & Behav Sci, Charleston, SC USA. MUSC, Dept Psychiat & Behav Sci, Ctr Drug & Alcohol Programs, Charleston, SC USA. NIDA, NIH, Bethesda, MD USA. RP DeVane, CL (reprint author), Med Univ S Carolina, Dept Psychiat, 67 President St,Room 246 N, Charleston, SC 29425 USA. EM devaneL@musc.edu FU NCRR NIH HHS [M01 RR01070-18]; NIDA NIH HHS [N01 DA-98102] NR 25 TC 21 Z9 21 U1 0 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PY 2005 VL 44 IS 7 BP 753 EP 765 DI 10.2165/00003088-200544070-00006 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 945NF UT WOS:000230508500006 PM 15966757 ER PT J AU Baker, SD Li, J ten Tije, AJ Figg, WD Graveland, W Verweij, J Sparreboom, A AF Baker, SD Li, J ten Tije, AJ Figg, WD Graveland, W Verweij, J Sparreboom, A TI Relationship of systemic exposure to unbound docetaxel and neutropenia SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PLASMA-PROTEIN BINDING; ALPHA(1)-ACID GLYCOPROTEIN; CLINICAL PHARMACOKINETICS; MASS-SPECTROMETRY; HIGH-AFFINITY; IN-VITRO; POLYSORBATE-80; EXCIPIENTS; CANCER; DRUG AB Objective: Our objective was to evaluate the association between exposure to unbound docetaxel and neutropenia in patients with cancer and to identify factors influencing unbound docetaxel clearance. Methods: Docetaxel was administered once every 3 weeks at a dose of 75 mg/m(2) to 49 patients with normal liver function (n = 40, group 1) or mild elevations in liver function test results (n = 9, group 2) or at a dose of 50 mg/m(2) to patients with moderate elevations in liver function test results (n = 6, group 3). Pharmacokinetic studies and toxicity assessments were performed during the first cycle of therapy. Total docetaxel concentrations were determined by HPLC and tandem mass spectrometry, and unbound docetaxel fraction was determined by equilibrium dialysis. Results: In patients with normal liver function, unbound docetaxel disposition was characterized by me-an (+/-SD) maximum plasma concentration (C-max), area under the curve (AUC), and clearance values of 233 +/- 101 ng/mL, 32 +/- 143 ng/mL (.) h, and 565 +/- 329 L/h, respectively. Unbound clearance varied 8.5-fold; polysorbate 80 exhibited mean (+/-SD) C-max, and clearance values of 451 +/- 221 mug/mL, 528 +/- 217 mug/mL (.) h, and 8.18 +/- 3.66 L/h, respectively; and clearance varied 6.7-fold. Unbound docetaxel clearance was reduced in patients with moderate liver impairment (groups 1 and 2 versus group 3, P = .020). From multiple linear regression analysis, only polysorbate 80 AUG and liver impairment were significantly associated with unbound docetaxel clearance. Both unbound docetaxel AUG and total AUG were correlated with the percentage decrements in absolute neutrophil count (P = .002 and P = .029, respectively), as well as the worst grade of neutropenia (P = .013 and P = .220, respectively), where higher exposure was associated with worse hematologic toxicity. Conclusions: Exposure to unbound docetaxel is closely related to drug-induced hematologic toxicity and should be considered in future pharmacologic investigations. C1 Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. NCI, Bethesda, MD 20892 USA. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. RP Baker, SD (reprint author), Sidney Kimmel Comprehens Canc Ctr, Bunting Blaustein Canc Res Bldg,1650 Orleans St R, Baltimore, MD 21231 USA. EM sdbaker@jhmi.edu RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 28 TC 50 Z9 50 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2005 VL 77 IS 1 BP 43 EP 53 DI 10.1016/j.clpt.2004.09.005 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 888NF UT WOS:000226380800005 PM 15637530 ER PT J AU Weinberger, DR AF Weinberger, DR TI Genetic mechanisms of psychosis: In vivo and postmortem genomics SO CLINICAL THERAPEUTICS LA English DT Article; Proceedings Paper CT 5th International Psychiatry Forum on Mind Matters CY JUN 19, 2004 CL Versailles, FRANCE SP Sanofi Aventis DE schizophrenia/genetics; genetic predisposition to disease; cerebral cortex/physiopathology ID DORSOLATERAL PREFRONTAL CORTEX; WORKING-MEMORY; SCHIZOPHRENIA; GRM3; RISK; GLUTAMATE; SIBLINGS; GENOTYPE; DISORDER; COMT AB Background: The Clinical Brain Disorders Branch Sibling Study data set was initiated in 1996 to examine genetic associations and to identify biological traits associated with susceptibility gene effects. Characterizing genes-and translating their effects on brain development and function-has potential Implications for improving the prevention and treatment of schizophrenia. Objective: The goal of this article was to discuss the relationship between genetic variation and schizophrenia using in vivo and postmortem genomics. Conclusions: Over the past 2 years, several specific genes have been convincingly associated with schizophrenia risk in a number of populations around the world. Some of the genes that have been studied more extensively include: catechol O-methyltransf erase (COMT) (chromosome 22q), dysbindin-1 (chromosome 6p), neuregulin 1 (chromosome 8p), metabotropic glutamate receptor 3 (GRM-3) (chromosome 7q), glutamate decarboxylase 1 (chromosome 2q), and disrupted-in-schizophrenia 1 (DISC1) (chromosome 1q). A functional polymorphism in the COMT gene, which affects prefrontal cortical function by changing dopamine signaling in the prefrontal cortex, has been studied extensively. This gene impacts the regulation of dopamine neuronal activity in the brainstem, which is associated with psychosis. GRM-3 shows similar results on prefrontal function; in postmortem tissue, it has an effect on expression of various glutamate synaptic markers. DISC1 affects hippocampal anatomy and function, whereas dysbindin-1 appears to be a general cognitive capacity gene that is underexpressed in the schizophrenic cortex. Data suggest that these susceptibility genes influence the cortical information processing which characterizes the schizophrenic phenotype. These data add to the evidence that such genes contribute to the pathophysiology of schizophrenia and provide insights into their mechanisms. Thus, genetic variation and its influence on the biological processes underlying schizophrenia may be key to developing future prevention strategies and new treatments. C1 NIH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Room 4S-235,10 Ctr Dr, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov NR 21 TC 26 Z9 27 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 2005 VL 27 SU A BP S8 EP S15 DI 10.1016/j.clinthera.2005.07.016 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 956NT UT WOS:000231307600003 PM 16198200 ER PT J AU Mitchell, R Shah, M Ahmad, S Rogers, AS Ellenberg, JH AF Mitchell, R Shah, M Ahmad, S Rogers, AS Ellenberg, JH CA Adolescent Trials Networks HIV TI A unified web-based Query and Notification System (QNS) for subject management, adverse events, regulatory, and IRB components of clinical trials SO CLINICAL TRIALS LA English DT Article ID WORLD-WIDE-WEB AB Even after intensive review, interpretative questions, ambiguities, contradictions, or errors, will arise once the protocol is scrutinized by site IRBs and implemented at sites. This will occur despite preparation and implementation of site protocol training, and provision of well crafted case report forms for the reporting of clinical and laboratory evaluations and adverse events. Since many staff are involved in each protocol, site investigators or study coordinators might direct protocol queries, participant management, or IRB queries to different network participants, resulting in inconsistent responses. It is important to establish a response mechanism that ensures consistent responses and their systematic documentation. For reporting of adverse events, and the submission of or documentation of completion of regulatory requirements, an easily accessible and structured communications system is also required. This paper describes the development and implementation of a user-friendly web-based query and notification system (QNS) for subject management, adverse events, regulatory, and IRB components. This system was created in the Adolescent Trials Network for HIV/AIDS Interventions (ATN), using existing web based tools with minor modifications and minimal cost. The query and notification system is interactive and allows for free flow of information among the site coordinators and both the protocol teams and the regulatory group. The process of the system is transparent to users at the sites, although its use and maintenance is controlled by Data Operations Center staff, to assure that ATN requirements for review and approval are met. This results in consistency of and timeliness of responses to queries, timeliness and accuracy of adverse event reporting and the ability for the data operations center regulatory staff to provide notification of pending or delinquent regulatory submissions. C1 Westat Corp, Rockville, MD USA. NICHHD, Pediat & Adolescent, Bethesda, MD 20892 USA. NICHHD, Maternal AIDS Branch, Bethesda, MD 20892 USA. RP Ellenberg, JH (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 423 Guardian Dr,604 Blockley Hall, Philadelphia, PA 19104 USA. EM JEllenbe@cceb.upenn.edu FU NICHD NIH HHS [U01 HD040474, U01 HD040533, U01-HD40474] NR 15 TC 8 Z9 8 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 1 BP 61 EP 71 DI 10.1191/1740774505cn68oa PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 974WQ UT WOS:000232622500009 PM 16279580 ER PT J AU Walton, M Simon, R Rockhold, F DuMouchel, W Koch, G O'Neill, R AF Walton, M Simon, R Rockhold, F DuMouchel, W Koch, G O'Neill, R TI Panel discussion of case study 3 SO CLINICAL TRIALS LA English DT Editorial Material C1 US FDA, Div Therapeut Biol Internal Med, Rockville, MD 20857 USA. NCI, Biometr Res Branch, Bethesda, MD USA. Univ N Carolina, Sch Publ Hlth, Biometr Consulting Lab, Dept Biostat, Chapel Hill, NC USA. US FDA, Off Biostat, Ctr Devices & Radiol Hlth, Rockville, MD USA. RP Walton, M (reprint author), US FDA, Div Therapeut Biol Internal Med, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 4 BP 352 EP 358 DI 10.1191/1740774505cn106oa PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 975GD UT WOS:000232648100014 ER PT J AU Dixon, BS Beck, GJ Dember, LM Depner, TA Gassman, JJ Greene, T Himmelfarb, J Hunsicker, LG Kaufman, JS Lawson, JH Meyers, CM Middleton, JP Radeva, M Schwab, SJ Whiting, JF Feldman, HI AF Dixon, BS Beck, GJ Dember, LM Depner, TA Gassman, JJ Greene, T Himmelfarb, J Hunsicker, LG Kaufman, JS Lawson, JH Meyers, CM Middleton, JP Radeva, M Schwab, SJ Whiting, JF Feldman, HI CA DAC Study Grp TI Design of the Dialysis Access Consortium (DAC) Aggrenox prevention of access stenosis trial SO CLINICAL TRIALS LA English DT Article ID MUSCLE-CELL-PROLIFERATION; HUMAN ARTERIOVENOUS-FISTULAS; RANDOMIZED CONTROLLED-TRIAL; VEIN-GRAFT PATENCY; LOW-DOSE ASPIRIN; VASCULAR ACCESS; HEMODIALYSIS-PATIENTS; ANTIPLATELET THERAPY; DOUBLE-BLIND; BLOOD-FLOW AB Background Surgically created arteriovenous (AV) grafts are the most common type of hemodialysis vascular access in the United States, but fail frequently due to the development of venous stenosis. The Dialysis Access Consortium (DAC) Aggrenox Prevention of Access Stenosis Trial tests the hypothesis that Aggrenox (containing dipyridamole and aspirin) can prevent stenosis and prolong survival of arteriovenous grafts. Methods This is a multicenter, randomized, double-blind, placebo-controlled trial that will enroll 1056 subjects over four years with one-half year follow-up. Subjects undergoing placement of a new AV graft for hemodialysis are randomized to treatment with Aggrenox or placebo immediately following access surgery. The primary outcome is primary unassisted patency defined as the time from access placement until thrombosis or an access procedure carried out to maintain or restore patency. The major secondary outcome is cumulative access patency. Monthly access flow monitoring is incorporated in the study design to enhance detection of a hemodynamically significant access stenosis before it leads to thrombosis. Results This paper describes the key issues in trial design, broadly including: 1) ethical issues surrounding the study of a clinical procedure that, although common, is no longer the clinical intervention of choice; 2) acceptable risk (bleeding) from the primary intervention; 3) inclusion of subjects already receiving a portion of the study intervention; 4) inclusion of subjects with incident rather than prevalent qualifying clinical conditions; 5) timing of the study intervention to balance safety and efficacy concerns; and 6) the selection of primary and secondary study endpoints. Conclusions This is the first, large, multicenter trial evaluating a pharmacologic approach to prevent AV graft stenosis and failure, an important and costly problem in this patient population. Numerous design issues were addressed in implementing the trial and these will form a roadmap for future trials in this area. C1 Vet Affairs Med Ctr, Iowa City, IA 52242 USA. Univ Iowa, Sch Med, Iowa City, IA 52242 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Calif Davis, Sch Med, Sacramento, CA USA. Maine Med Ctr, Portland, ME USA. Duke Univ, Ctr Med, Durham, NC USA. Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA. Univ Penn, Sch Med, Philadelphia, PA USA. RP Dixon, BS (reprint author), Vet Affairs Med Ctr, Iowa City, IA 52242 USA. EM bradley-dixon@uiowa.edu FU NIDDK NIH HHS [U01DK058968, U01 DK058986, U01DK058966, U01DK058973, U01DK058978, U01DK058981, U01DK058982, U01DK058985, U01DK058986] NR 61 TC 24 Z9 24 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 5 BP 400 EP 412 DI 10.1191/1740774505cn110oa PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 982RH UT WOS:000233178800004 PM 16317809 ER PT J AU Dember, LM Kaufman, JS Beck, GJ Dixon, BS Gassman, JJ Greene, T Himmelfarb, J Hunsicker, LG Kusek, JW Lawson, JH Middleton, JP Rodeva, M Schwab, SJ Whiting, JF Feldman, HI AF Dember, LM Kaufman, JS Beck, GJ Dixon, BS Gassman, JJ Greene, T Himmelfarb, J Hunsicker, LG Kusek, JW Lawson, JH Middleton, JP Rodeva, M Schwab, SJ Whiting, JF Feldman, HI CA DAC Study Grp TI Design of the Dialysis Access Consortium (DAC) clopidogrel prevention of early AV fistula thrombosis trial SO CLINICAL TRIALS LA English DT Article ID ARTERIOVENOUS-FISTULAS; VASCULAR ACCESS; HEMODIALYSIS-PATIENTS; NONINVASIVE EVALUATION; ACETYLSALICYLIC-ACID; PLATELET ACTIVITY; UNITED-STATES; DOUBLE-BLIND; TICLOPIDINE; DISCONTINUATION AB Background The Dialysis Access Consortium (DAC) was developed to investigate interventions to improve hemodialysis vascular access outcomes. The autogenous arteriovenous fistula created by direct connection of native artery to vein is the recommended vascular access for hemodialysis. However, it fails frequently due to clotting after surgery. Purpose The DAC Early AV Fistula Thrombosis Trial tests the hypothesis that clopidogrel can prevent early fistula failure and increase the number of fistulas that ultimately become usable for hemodialysis access. This is one of two initial and concurrent trials being performed by the DAC. The companion trial investigates pharmacologic approaches to prevent venous stenosis leading to AV graft failure. Methods This is a multicenter, randomized, double-blind, placebo-controlled trial that will enroll 1284 patients over four years. Patients undergoing creation of a new native arteriovenous (AV) fistula are randomized to treatment with clopidogrel or placebo for six weeks following fistula creation surgery. The primary outcome is fistula patency at six weeks. The major secondary outcome is fistula suitability for dialysis. Results This paper examines key aspects of this study that have broad relevance to trial design including: 1) the selection of an intermediate event as the primary outcome, 2) timing of the intervention to balance efficacy and safety concerns, 3) ethical considerations arising from required modifications of concomitant drug therapy, and 4) choosing an efficacy or effectiveness evaluation of the intervention. Conclusions This is the first, large, multicenter trial evaluating a pharmacologic approach to prevent early AV fistula failure and promote more usable fistulas for hemodialysis. The methodologic challenges identified and addressed during the development of this trial should help to inform the design of future vascular access trials, and are relevant to clinical trials addressing a wide range of questions. C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Iowa, Iowa City, IA USA. Maine Med Ctr, Portland, ME 04102 USA. Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA. Duke Univ, Ctr Med, Durham, NC USA. Univ Penn, Sch Med, Philadelphia, PA USA. Med Coll Georgia, Augusta, GA USA. RP Dember, LM (reprint author), Boston Univ, Sch Med, EBRC 504,650 Albany St, Boston, MA 02118 USA. EM ldember@bu.edu FU NIDDK NIH HHS [U01DK058973, U01 DK058986, U01DK058966, U01DK058968, U01DK058978, U01DK058981, U01DK058982, U01DK058985, U01DK058986] NR 39 TC 32 Z9 33 U1 0 U2 5 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 5 BP 413 EP 422 DI 10.1191/1740774505cn118oa PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 982RH UT WOS:000233178800005 PM 16317810 ER PT J AU Palevsky, PM O'Connor, T Zhang, JHY Star, RA Smith, MW AF Palevsky, PM O'Connor, T Zhang, JHY Star, RA Smith, MW CA VA NIH Acute Renal Failure Trial N TI Design of the VA/NIH Acute Renal Failure Trial Network (ATN) study: intensive versus conventional renal support in acute renal failure SO CLINICAL TRIALS LA English DT Article ID CONTINUOUS VENOVENOUS HEMOFILTRATION; RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; REPLACEMENT THERAPY; RANDOMIZED-TRIAL; TIDAL VOLUMES; CARE-UNIT; DIALYSIS; INTERMITTENT; HEMODIALYSIS AB The optimal management of renal replacement therapy (RRT) in acute renal failure (ARF) is uncertain. The VA/NIH Acute Renal Failure Trail Network Study (ATN Study) tests the hypothesis that a strategy of intensive RRT will decrease 60-day all-cause mortality in critically ill patients with ARF. Dose separation between the two treatment arms is achieved by increasing the frequency of intermittent hemodialysis (IHD) and sustained low efficiency dialysis (SLED) treatments from three times per week to six times per week, and by increasing continuous venovenous hemodiafiltration (CVVHDF) effluent volume from 20 mL/kg/hr to 35 mL/kg/hr. In both treatment arms, subjects convert between IHD and CVVHDF or SLED as hemodynamic status changes over time. This strategy attempts to replicate the conversion between modalities of RRT that occurs in clinical practice. However, in order to implement this strategy, flexible criteria needed to be developed to provide a balance between the need for uniformity of treatment between groups and practitioner discretion regarding modality of RRT to maintain patient safety. In order to address safety and ethical issues similar to those raised by the Office of Human Research Protections in its review of the ARDS Network studies, a survey of practitioner practices was performed and observational data on the management of RRT in comparable critically ill patients with ARF managed outside of the research context is being collected prospectively. These data will help inform the study's DSMB and site IRB's of the relationship between the study's treatment arms and concurrent clinical practice. C1 VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. VA Connecticut Healthcare Syst, Cooperat Studies Program, Coordinating Ctr, West Haven, CT USA. Natl Inst Hlth, Natl Inst Diab Digest & Kidney Dis, Bethesda, MD USA. VA Palo Alto Hlth Care Syst, Hlth Econ Resouce Ctr, Menlo Pk, CA USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Univ Dr, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu RI Smith, Mark/G-1522-2012; OI Smith, Mark/0000-0002-4582-9088; Palevsky, Paul/0000-0002-7334-5400 FU NIDDK NIH HHS [Y1-DK-3508-01/02/03, Y01 DK003508, Y01 DK003508-01, Y01 DK003508-02, Y01 DK003508-03, Y1-DK-3508-01] NR 35 TC 60 Z9 65 U1 0 U2 1 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 5 BP 423 EP 435 DI 10.1191/1740774505cn116oa PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 982RH UT WOS:000233178800006 PM 16317811 ER PT J AU Cook, ED Moody-Thomas, S Anderson, KB Campbell, R Hamilton, SJ Harrington, JM Lippman, SM Minasian, LM Paskett, ED Craine, S Arnold, KB Probstfield, JL AF Cook, ED Moody-Thomas, S Anderson, KB Campbell, R Hamilton, SJ Harrington, JM Lippman, SM Minasian, LM Paskett, ED Craine, S Arnold, KB Probstfield, JL TI Minority recruitment to the Selenium and Vitamin E Cancer Prevention Trial (SELECT) SO CLINICAL TRIALS LA English DT Article ID COOPERATIVE-ONCOLOGY-GROUP; CLINICAL-TRIALS; AFRICAN-AMERICANS; PROSTATE-CANCER; PARTICIPATION; MEN; SURVIVAL; RACE AB Background Previous large chemoprevention studies have not recruited significant numbers of minorities. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is a large phase III study evaluating the impact of selenium and vitamin E on the clinical incidence of prostate cancer. Over 400 SELECT study sites in the USA, Canada, and Puerto Rico recruited men to this trial. The SELECT recruitment goal was 24% minorities, with 20% black, 3% Hispanic, and 1% Asian participants. The goal for black participants was set at 20% because of their proportion in the United States population and their prevalence of prostate cancer. Methods The minority recruitment strategies in SELECT were to: 1) consider minority recruitment during site selection; 2) expand the eligibility criteria by lowering the age criterion for black men and including men with controlled co-morbid illnesses; 3) develop a national infrastructure; 4) give additional funds to sites with the potential to increase black enrollment; and 5) provide resources to maximize free media opportunities to promote SELECT. Results SELECT recruitment began in August 2001 and was intended to last five years, but concluded two years ahead of schedule in June 2004. Of the 35 534 participants enrolled, 21% were minorities, with 15% black, 5% Hispanic, and 1% Asian. Conclusions Careful planning, recruitment of large numbers of clinical centers and adequate resources accomplished by the combined efforts of the National Cancer Institute (NCl), Southwest Oncology Group (SWOG), SELECT Recruitment and Adherence Committee (RAC), SELECT Minority and Medically Underserved Subcommittee (MMUS), and the local SELECT sites resulted in attainment of the estimated sample size ahead of schedule and recruitment of the largest percentage of black participants ever randomized to a cancer prevention trial. C1 Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent Unit, U1360, Houston, TX 77230 USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. SW Oncol Grp, Stat Ctr, Seattle, WA USA. Morehouse Sch Med, Atlanta, GA USA. Rush Univ, Ctr Med, Chicago, IL USA. Natl Canc Inst, Bethesda, MD USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Washington, Cooperat Studies Program, Dept Vet Affairs, Seattle, WA USA. RP Cook, ED (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent Unit, U1360, Post Off Box 301439, Houston, TX 77230 USA. EM edcook@mdanderson.org FU NCI NIH HHS [5-U10-CA-37429] NR 32 TC 32 Z9 33 U1 1 U2 2 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 5 BP 436 EP 442 DI 10.1191/1740774505cn111oa PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 982RH UT WOS:000233178800007 PM 16315648 ER PT J AU Guimaraes, P Kieburtz, K Goetz, CG Elm, JJ Palesch, YY Huang, P Ravina, B Tanner, CM Tilley, BC AF Guimaraes, P Kieburtz, K Goetz, CG Elm, JJ Palesch, YY Huang, P Ravina, B Tanner, CM Tilley, BC TI Non-linearity of Parkinson's disease progression: implications for sample size calculations in clinical trials SO CLINICAL TRIALS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; INITIAL TREATMENT; LEVODOPA; NEUROPROTECTION; PRAMIPEXOLE; ROPINIROLE; DECLINE; 5-YEAR AB Background Estimation of sample size for long-term studies of neuroprotection in Parkinson's disease requires information on expected clinical decline. Values may be obtained by analyzing existing long-term data sets or by prediction models of clinical decline applied to available data from shorter-term trials. The most commonly used measure to track clinical decline is the Unified Parkinson's Disease Rating Scale (UPDRS) but this measure is also affected by symptomatic therapy. Models can help better understand behavior of the UPDRS after initiation of symptomatic therapy when scores will improve and eventually start deteriorating again. Purpose To understand how UPDRS scores progress after initiation of symptomatic therapy and how this progression impacts sample size calculations. Methods We developed a non-linear model of UPDRS after introduction of symptomatic therapy. The model is specified as a non-linear mixed effects model and is applied to three different data sets from clinical trials. The model is then used to produce estimates for the change in UPDRS and its associated variance for a period of up to five years of follow-up. The estimates produced by the model serve as the basis for sample-size calculations for different lengths of follow-up (one through five years) and for different values of clinically meaningful change in UPDRS. Results Despite differences in the short-term benefit of the dopaminergic drugs, after a period of approximately six months UPDRS scores progress linearly at an estimated rate of approximately three points a year. The sample size that is required for a clinical trial where the baseline coincides with initiation of symptomatic therapy is very large. On the other hand, if baseline is set at six months after initiation of symptomatic therapy then the sample size required decreases with length of follow-up. Limitations Model specification and estimation is based on a set of simplifying assumptions regarding the progression of individual level UPDRS scores. Conclusions Sample size calculations based on these estimates indicate a substantial reduction in sample size if patients are required to be on symptomatic treatment for a period of time before being randomized to a neuroprotective trial. C1 Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. Univ Rochester, Clin Trials Coordinat Ctr, Dept Neurol, Rochester, NY USA. Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. NINDS, Ctr Neurosci, NIH, Bethesda, MD 20892 USA. Parkinsons Inst, Sunnyvale, CA USA. RP Guimaraes, P (reprint author), Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, 135 Cannon St,Suite 303, Charleston, SC 29425 USA. EM guimarap@musc.edu RI Guimaraes, Paulo/A-7085-2008 OI Guimaraes, Paulo/0000-0002-2992-1028 FU NINDS NIH HHS [U01NS43128, U01NS043127] NR 24 TC 18 Z9 18 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 6 BP 509 EP 518 DI 10.1191/1740774505cn125oa PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 005LD UT WOS:000234822800005 PM 16422311 ER PT J AU Geller, NL Sorlie, P Coady, S Fleg, J Manolio, T Friedman, L AF Geller, NL Sorlie, P Coady, S Fleg, J Manolio, T Friedman, L TI Untitled SO CLINICAL TRIALS LA English DT Letter C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Geller, NL (reprint author), NHLBI, NIH, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM gellern@nhlbi.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 6 BP 538 EP 538 DI 10.1191/1740774505cn124xx PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 005LD UT WOS:000234822800008 PM 16422314 ER PT J AU Rifai, MA Loftis, JM Hauser, P AF Rifai, MA Loftis, JM Hauser, P TI Interferon-alpha treatment of patients with hepatitis C - The role of a comprehensive risk-benefit assessment SO CNS DRUGS LA English DT Letter ID PSYCHIATRIC-DISORDERS; MANAGEMENT; INFECTION C1 NIMH, NIH, Bethesda, MD 20892 USA. Portland VA Med Ctr, Behavioral Hlth & Clin Neurosci Div, Portland, OR USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. NW Hepatitis C Resource Ctr, Portland, OR USA. Portland VA Med Ctr, JENS Lab, Portland, OR USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. RP Rifai, MA (reprint author), NIMH, NIH, Bethesda, MD 20892 USA. NR 9 TC 4 Z9 4 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2005 VL 19 IS 8 BP 719 EP 721 DI 10.2165/00023210-200519080-00009 PG 3 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 956UJ UT WOS:000231325100009 PM 16097855 ER PT J AU Read, JS Newell, ML AF Read, J. S. Newell, M. L. TI Efficacy and safety of cesarean delivery for prevention of mother-to-child transmission of HIV-1 SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTED PREGNANT-WOMEN; VERTICAL TRANSMISSION; MATERNAL COMPLICATIONS; ANTIRETROVIRAL THERAPY; HIV-1-INFECTED WOMEN; POSTPARTUM MORBIDITY; VAGINAL DELIVERY; POSITIVE WOMEN; SECTION AB Background Cesarean section before labor and before ruptured membranes ("elective cesarean section", or ECS) has been introduced as an intervention for the prevention of mother-to-child transmission (MTCT) of HIV-1. The role of mode of delivery in the management of HIV-1-infected women should be assessed in light of risks as well as benefits, since HIV-1-infected pregnant women must be provided with available information with which to make informed decisions regarding cesarean section and other options to prevent transmission of infection to their children. Objectives Our objectives were to assess the efficacy (for prevention of MTCT of HIV-1) and the safety of ECS among HIV-1-infected women. Search strategy Electronic searches were undertaken using MEDLINE and other databases. Hand searches of reference lists of pertinent reviews and studies, as well as abstracts from relevant conferences, were also conducted. Experts in the field were contacted to locate any other studies. The search strategy was iterative. Selection criteria Randomized clinical trials assessing the efficacy and safety of ECS for prevention of MTCT of HIV-1 were included in the analysis, as were observational studies with relevant data. Data collection and analysis Data regarding HIV-1 infection status of infants born to HIV-1-infected women according to mode of delivery were extracted from the reports of the studies. Similarly, data regarding postpartum morbidity (PPM) ( including minor ( e. g., febrile morbidity, urinary tract infection) and major (e. g., endometritis, thromboembolism) morbidity) of the HIV-1-infected women, and infant morbidity, according to mode of delivery were extracted. Main results One randomized clinical trial of the efficacy of ECS for prevention of MTCT of HIV-1 was identified. No data regarding infant morbidity according to the HIV-1-infected mother's mode of delivery were available. Data regarding PPM according to mode of delivery were available from this clinical trial as well as from five observational studies. Among HIV-1-infected women not taking antiretrovirals (ARVs) during pregnancy or taking only zidovudine, ECS was found to be efficacious for prevention of MTCT of HIV-1. PPM is generally higher among HIV-1-infected women who undergo cesarean as compared to vaginal delivery, with the risk with ECS being intermediate between that of vaginal delivery and NECS (including emergency procedures). Other factors associated with the risk of PPM among HIV-1-infected women include HIV-1 disease stage (more advanced disease, as manifested by lower CD4 counts and higher viral loads, being associated with a greater risk of PPM) and co-morbid conditions ( e. g., diabetes). Authors' conclusions ECS is an efficacious intervention for the prevention of MTCT among HIV-1-infected women not taking ARVs or taking only zidovudine. The risk of PPM with ECS is higher than that associated with vaginal delivery, yet lower than with NECS. Among HIV-1-infected women, more advanced maternal HIV-1 disease stage and concomitant medical conditions ( e. g., diabetes) are independent risk factors for PPM. The risk of MTCT of HIV-1 according to mode of delivery among HIV-1-infected women with low viral loads ( low either because the woman's HIV-1 disease is not advanced, or because her HIV-1 disease is well-controlled with ARVs) is unclear. Therefore, an important issue to be addressed in one or more large studies ( individual studies or an individual patient data meta-analysis combining data from more than one study) is assessment of the effectiveness of ECS for prevention of MTCT of HIV-1 among HIV-1-infected women with undetectable viral loads ( with or without receipt of highly active ARV therapy ( HAART)). C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA. RP Read, JS (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Execut Bldg,Room 4B11F,6100 Execut Blvd MSC 7510, Bethesda, MD 20892 USA. EM jr92o@nih.gov NR 37 TC 38 Z9 39 U1 0 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1469-493X J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2005 IS 4 AR CD005479 DI 10.1002/14651858.CD005479 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 096UK UT WOS:000241402100087 ER PT J AU Blair, RJR AF Blair, R. James R. BE Easton, A Emery, NJ TI The neurobiology of antisocial behaviour and psychopathy SO COGNITIVE NEUROSCIENCE OF SOCIAL BEHAVIOUR LA English DT Article; Book Chapter ID POSITRON-EMISSION-TOMOGRAPHY; ORBITOFRONTAL CORTEX DYSFUNCTION; PRESCHOOL CHILDRENS CONCEPTIONS; FRONTAL-LOBE DAMAGE; FACIAL EXPRESSIONS; PASSIVE-AVOIDANCE; CONDUCT PROBLEMS; PERSONALITY-DISORDERS; PREFRONTAL CORTEX; RESPONSE REVERSAL AB This chapter considers neurobiological influences on threat/frustration-based reactive aggressions and goal-directed instrumental aggression. Reactive aggression is mediated by a dedicated subcortical neural system that humans share with other mammalian species. It is suggested that this system is modulated by the amygdala and regions of the orbital and medial frontal cortex, and that dysfunction within these structures can dysregulate the individual's response to threat. Instrumental aggression is goal-directed motor activity; the aggression is used to achieve a particular goal such as obtaining another individual's money or increasing status within a group. Remarkable levels of instrumental aggression are displayed by individuals with psychopathy. Various models of instrumental aggression/psychopathy will be considered. However, it will be suggested that only the integrated emotion systems (IES) approach can account for the emergence of this disorder. C1 NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, 15K North Dr,Room 206,MSC 2670, Bethesda, MD 20892 USA. NR 211 TC 3 Z9 3 U1 1 U2 7 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH ROAD, HOVE BN3 2FA, E SUSSEX, ENGLAND BN 978-0-203-31187-5 PY 2005 BP 291 EP 324 DI 10.4324/9780203311875_chapter_10 D2 10.4324/9780203311875 PG 34 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA BRB69 UT WOS:000282323800010 ER PT J AU Grafman, J Spector, L Rattermann, MJ AF Grafman, Jordan Spector, Lee Rattermann, Mary Jo BE Morris, R Ward, G TI Planning and the brain SO COGNITIVE PSYCHOLOGY OF PLANNING SE Current Issues in Thinking and Reasoning LA English DT Article; Book Chapter ID SPATIAL WORKING-MEMORY; FRONTAL-LOBE LESIONS; POSITRON-EMISSION-TOMOGRAPHY; HUMAN PREFRONTAL CORTEX; TOWER-OF-LONDON; PARKINSONS-DISEASE; TASK; DAMAGE; PERSPECTIVES; ACTIVATION C1 [Grafman, Jordan] NINDS, Cognit Neurosci Sect, Bethesda, MD 20892 USA. [Spector, Lee] Hampshire Coll, Dept Cognit & Computat Sci, Amherst, MA 01002 USA. [Rattermann, Mary Jo] Franklin & Marshall Coll, Dept Psychol, Lancaster, PA 17604 USA. [Spector, Lee] Hampshire Coll, Sch Cognit Sci, Amherst, MA 01002 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, Bldg 10,Rm 5C205,10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. NR 72 TC 10 Z9 10 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH ROAD, HOVE BN3 2FA, E SUSSEX, ENGLAND BN 978-0-203-49356-4 J9 CURR ISS THINK REASO PY 2005 BP 181 EP 198 PG 18 WC Psychology, Experimental SC Psychology GA BUO85 UT WOS:000289943300009 ER PT J AU Pinsky, PF AF Pinsky, PF TI Scaling of true and apparent ROC AUC with number of observations and number of variables SO COMMUNICATIONS IN STATISTICS-SIMULATION AND COMPUTATION LA English DT Article DE biomarkers; model mis-specification; overfitting; ROC AUC ID CLASSIFICATION; CANCER; CURVE AB New technologies have recently emerged which enable simultaneous evaluation of large numbers of biological markers. The resultant marker data are often used to build predictive models which claim to be able to distinguish between two or more classes of subjects. However, when there are a large number of variables and a small number of observations, the problem of overfitting arises, where the model parameters are optimized for the observed data but may fit poorly for independent data. Here we illustrate how various quantities related to true and apparent predictive ability scale with the number of markers and the number of observations (subjects). Specifically, we utilize a model which takes the form of a linear combination of a subset of marker variables; the model produces a propensity score which generates an ROC curve and corresponding area under the ROC curve (AUC), which is a measure of predictive ability. Given the true marker distributions, there is a parameter value so that the resulting predictive model gives the optimal true AUC. In practice, the true distributions are unknown, so experimental data are used to derive a parameter value which produces the optimal apparent AUC, where the "apparent" AUC is based on the observed instead of the true distributions. If the above model with the estimated optimal parameter is then used on an independent data set, it would have an actual AUC derived from the estimated optimal parameter and the true marker distributions. The difference between the apparent AUC and the actual AUC can be denoted as the total error in estimating predictive ability. This total error can be additively decomposed into the "overfitting error", namely, the apparent AUC minus the optimal AUC, and the "mis-specification error", namely the optimal A UC minus the actual AUC. We focus here on how these errors scale with the number of observations and the number of markers, where the latter are divided into "null" markers which contain no information as to class status and "associated" markers which are related to class status. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Pinsky, PF (reprint author), NCI, Div Canc Prevent, 6130 Execut Blvd, Bethesda, MD 20892 USA. EM pp4f@nih.gov NR 10 TC 3 Z9 3 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-0918 J9 COMMUN STAT-SIMUL C JI Commun. Stat.-Simul. Comput. PY 2005 VL 34 IS 3 BP 771 EP 781 DI 10.1081/SAC-200068366 PG 11 WC Statistics & Probability SC Mathematics GA 961PM UT WOS:000231674300018 ER PT J AU Liu, AY Schisterman, EF Wu, CQ AF Liu, AY Schisterman, EF Wu, CQ TI Nonparametric estimation and hypothesis testing on the partial area under receiver operating characteristic curves SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE accuracy of diagnostic tests; biomarkers; Mann-Whitney statistics; sensitivity; specificity ID MAXIMUM-LIKELIHOOD-ESTIMATION; CHARACTERISTIC ROC CURVES; DIAGNOSTIC-ACCURACY; BINORMAL MODEL; DESIGN AB The area under a receiver operating characteristic curve is a useful index of the accuracy of a diagnostic test. When the diagnostic ability of a new biomarker is of interest only in a certain range of specificity, the partial area under the curve becomes desirable. In this article, we extend Bamber's (1975) results and show that the partial area under a receiver operating characteristic curve is the probability of a constrained stochastic ordering. We then construct a 'weighted' Mann-Whitney statistic as an estimator of the partial area and investigate its statistical properties. A testing procedure is also developed to compare partial area under two receiver operating characteristic curves. The methods are exemplified with data from biomarkers associated with coronary heart disease. C1 NICHHD, Biometry & Math Stat Branch, DHHS, DESPR, Rockville, MD 20852 USA. Univ Sci & Technol China, Dept Stat & Finance, Hefei, Anhui, Peoples R China. RP Liu, AY (reprint author), NICHHD, Biometry & Math Stat Branch, DHHS, DESPR, 6100 Execut Blvd, Rockville, MD 20852 USA. EM liua@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082; Schisterman, Enrique/0000-0003-3757-641X NR 21 TC 10 Z9 10 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-0926 J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 2005 VL 34 IS 9-10 BP 2077 EP 2088 DI 10.1080/03610920500203786 PG 12 WC Statistics & Probability SC Mathematics GA 968BT UT WOS:000232137600016 ER PT S AU Vinogradova, TM Maltsev, VA Bogdanov, KY Lyashkov, AE Lakatta, EG AF Vinogradova, TM Maltsev, VA Bogdanov, KY Lyashkov, AE Lakatta, EG BE Sideman, S Beyar, R Landesberg, A TI Rhythmic Ca2+ oscillations drive sinoatrial nodal cell pacemaker function to make the heart tick SO COMMUNICATIVE CARDIAC CELL SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd Larry and Horti Fairberg Cardiac Workshop on Communicative Cardiac Cell CY JAN 15-19, 2005 CL Sintra, PORTUGAL SP Israel Inst Technol, Technion, Portugal Minist Sci & Technol DE beta-adrenergic receptor stimulation; local Ca2+ release; ryanodine receptor; sinoatrial nodal cells ID NA+-CA2+ EXCHANGE CURRENT; CAT RIGHT ATRIUM; SARCOPLASMIC-RETICULUM; RYANODINE RECEPTOR; CALCIUM-RELEASE; INTRACELLULAR CALCIUM; DIASTOLIC DEPOLARIZATION; MATHEMATICAL-MODEL; ACTION-POTENTIALS; BEATING RATE AB Excitation-induced Ca2+ cycling into and out of the cytosol via the sarcoplasmic reticulum (SR) Ca2+ pump, ryanodine receptor (RyR) and Na+-Ca2+ exchanger (NCX) proteins, and modulation of this Ca(2+)cycling by beta-adrenergic receptor (beta-AR) stimulation, governs the strength of ventricular myocyte contraction and the cardiac contractile reserve. Recent evidence indicates that heart rate modulation and chronotropic reserve via beta-ARs also involve intracellular Ca2+ cycling by these very same molecules. Specifically, sinoatrial nodal pacemaker cells (SANC), even in the absence of surface membrane depolarization, generate localized rhythmic, submembrane Ca2+ oscillations via SR Ca2+ pumping-RyR Ca2+ release. During spontaneous SANC beating, these rhythmic, spontaneous Ca2+ oscillations are interruyted by the occurrence of an action potential (AP), which activates L-type Ca2+ channels to trigger SR Ca2+ release, unloading the SR Ca2+ content and inactivatingRYRs. During the later part of the subsequent diastolic depolarization (DD), when Ca2+ pumped back into the SR sufficiently replenishes the SR Ca2+ content, and Ca2+-dependent RyR inactivation wanes, the spontaneous release of Ca2+ via RyRs again begins to occur. The local increase in submembrane [Ca2+] generates an inward current via NCX, enhancing the DD slope, modulating the occurrence of the next AP, and thus the beating rate. beta-AR stimulation increases the submembrane Ca2+ oscillation amplitude and reduces the period (the time from the prior AP triggered SR Ca2+ release to the onset of the local Ca2+ release during the subsequent DD). This increased amplitude and phase shift causes the NCX current to occur at earlier times following a prior beat, promoting the earlier arrival of the next beat and thus an increase in the spontaneous firing rate. Ca2+ cycling via the SR Ca2+ pump, RyR and NCX, and its modulation by beta-AR stimulation is, therefore, a general mechanism of cardiac chronotropy and inotropy. C1 NIA, Lab Cardiovasc Sci, Intramural Res Program, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Lab Cardiovasc Sci, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM lakattae@grc.nia.nih.gov NR 53 TC 50 Z9 50 U1 0 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-547-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1047 BP 138 EP 156 DI 10.1196/annals.1341.013 PG 19 WC Cell Biology; Multidisciplinary Sciences SC Cell Biology; Science & Technology - Other Topics GA BCY65 UT WOS:000231874400013 PM 16093492 ER PT S AU Carmel, L Rogozin, IB Wolf, YI Koonin, EV AF Carmel, L Rogozin, IB Wolf, YI Koonin, EV BE McLysaght, A Huson, DH TI An expectation-maximization algorithm for analysis of evolution of exon-intron structure of eukaryotic genes SO COMPARATIVE GENOMICS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 3rd RECOMB International Workshop on Comparative Genomics CY SEP 18-20, 2005 CL Univ Dublin, Trinity Coll, Dublin, IRELAND SP Sci Fdn Ireland, Hewlett Packard HO Univ Dublin, Trinity Coll ID MAXIMUM-LIKELIHOOD; PHYLOGENETIC ESTIMATION; DNA-SEQUENCES; RATES; INSERTION; GAIN AB We propose a detailed model of evolution of exon-intron structure of eukaryotic genes that takes into account gene-specific intron gain and loss rates, branch-specific gain and loss coefficients, invariant sites incapable of intron gain, and rate variability of both gain and loss which is gamma-distributed across sites. We develop an expectation-maximization algorithm to estimate the parameters of this model, and study its performance using simulated data. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Carmel, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM carmel@ncbi.nlm.nih.gov; rogozin@ncbi.nlm.nih.gov; wolf@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov RI Carmel, Liran/A-9681-2008 NR 18 TC 7 Z9 8 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-28932-1 J9 LECT NOTES COMPUT SC PY 2005 VL 3678 BP 35 EP 46 PG 12 WC Biochemical Research Methods; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Biochemistry & Molecular Biology; Computer Science GA BDW52 UT WOS:000235841500004 ER PT J AU Grant, BF Stinson, FS Dawson, DA Chou, SP Ruan, WJ AF Grant, BF Stinson, FS Dawson, DA Chou, SP Ruan, WJ TI Co-occurrence of DSM-IV personality disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID III-R; BORDERLINE PERSONALITY; 5-FACTOR MODEL; COMORBIDITY; RELIABILITY; PREVALENCE; INTERVIEW; PATTERNS; SAMPLE AB The objective of this study was to determine the co-occurrence of 7 of the 10 Diagnosis and Statistical Manual of Mental Disorders. Fourth Edition. Text Revision (DSM-IV-TR) personality disorders (PDs) in the US population. Face-to-face interviews were conducted with 43093 respondents in the National Institute on Alcohol Abuse and Alcoholisms 2001-2002 National Epidemiologic Surrey on alcohol and Related Conditions, a nationally representative survey of the US population. Odds ratios were calculated to determine associations among PDs. All associations among PDs were positive and statistically significant. PDs were significantly associated with other PDs thin the same cluster, in addition to being highly associated with PDs of other DSM-IV PD clusters. Co-occurrence between DSM-IV PDs is pervasive in the US general population. Future research is needed on the creation of dimensional representation: of DSH-IV PDs as an adjunct to categorical diagnoses. Published by Elsevier Inc. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov NR 25 TC 94 Z9 95 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JAN-FEB PY 2005 VL 46 IS 1 BP 1 EP 5 DI 10.1016/j.cornppsych.2004.07.019 PG 5 WC Psychiatry SC Psychiatry GA 886YN UT WOS:000226269100001 PM 15714187 ER PT J AU Fukumoto, S Yamada, Y AF Fukumoto, S Yamada, Y TI Review: Extracellular matrix regulates tooth morphogenesis SO CONNECTIVE TISSUE RESEARCH LA English DT Review DE extracellular matrix; basement membrane; tooth; enamel; dentin ID LAMININ ALPHA-5 CHAIN; BASEMENT-MEMBRANE; EPITHELIAL-CELLS; EXPRESSION; GENE; MOUSE; AMELOGENIN; DIFFERENTIATION; AMELOBLASTIN; ENAMELIN AB Mineralized tissues are unique in that they use proteins to attract and organize calcium and phosphate ions into a structured mineral phase, thus precise knowledge of the expression and extracellular distribution of matrix proteins is very important to understand their function. Tooth development is regulated by sequential and reciprocal interactions between neural crest-derived mesenchymal cells and the oral environment. However, the precise molecular mechanisms that mediate interactions between epithelium and mesenchymal cells are not clear, although basement membrane (BM) components have been shown to play important roles in these regulatory events. In addition, the extracellular matrix layer, whose main components are laminin, collagen IV, nidogen, and sulfated proteoglycan, and the BM layer are both considered to be involved with cell proliferation and differentiation. During tooth morphogenesis, extracellular matrices are dramatically changed. Further, the BM components, laminin and collagen IV support dental epithelium; however, in the late stage, they begin the processes of enamel matrix secretion and calcification, after which the BM structure between the dental epithelium and mesenchyme disappears. In addition, tooth abnormalities associated with several kinds of human diseases that cause mutations in the extracellular matrix, as well as the molecular mechanisms of the basement membrane and enamel matrix during tooth morphogenesis, are not clearly understood. In our review, we discuss the role of the extracellular matrix, with focus on the BM and enamel matrix during tooth morphogenesis. C1 Kyushu Univ, Fac Dent Sci, Div Oral Hlth Growth & Dev, Sect Pediat Dent,Higashi Ku, Fukuoka 8128582, Japan. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. RP Fukumoto, S (reprint author), Kyushu Univ, Fac Dent Sci, Div Oral Hlth Growth & Dev, Sect Pediat Dent,Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. EM fukumoto@dent.kyushu-u.ac.jp NR 54 TC 33 Z9 34 U1 2 U2 11 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PY 2005 VL 46 IS 4-5 BP 220 EP 226 DI 10.1080/03008200500344017 PG 7 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA 013TZ UT WOS:000235434000009 PM 16546825 ER PT J AU Nadiminti, H Ehrlich, A Udey, MC AF Nadiminti, H Ehrlich, A Udey, MC TI Oral erosions as a manifestation of allergic contact sensitivity to cinnamon mints SO CONTACT DERMATITIS LA English DT Editorial Material DE allergic contact stomatitis; cinnamic aldehyde; mints; oral erosions ID ALDEHYDE; GUM C1 NCI, Canc Res Ctr, Dermatol Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Med, Dept Dermatol, Washington, DC USA. RP Udey, MC (reprint author), Bldg 10,Room 12N238,10 Ctr Dr, Bethesda, MD 20892 USA. EM udey@helix.nih.gov OI Ehrlich, Alison/0000-0002-4062-5289 NR 8 TC 8 Z9 9 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-1873 J9 CONTACT DERMATITIS JI Contact Dermatitis PD JAN PY 2005 VL 52 IS 1 BP 46 EP 47 DI 10.1111/j.0105-1873.2005.0483c.x PG 2 WC Allergy; Dermatology SC Allergy; Dermatology GA 895YB UT WOS:000226899300015 PM 15701132 ER PT S AU Morris, CR Kuypers, FA Kato, GJ Lavrisha, L Larkin, S Singer, T Vichinsky, EP AF Morris, CR Kuypers, FA Kato, GJ Lavrisha, L Larkin, S Singer, T Vichinsky, EP BE Vichinsky, EP TI Hemolysis-associated pulmonary hypertension in thalassemia SO COOLEY'S ANEMIA EIGHTH SYMPOSIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 8th Cooleys Anemia Symposium CY MAR 17-19, 2005 CL Lake Buena Vista, FL SP New York Acad Sci, Cooleys Anemia Fdn, Apopharm Inc, Natl Inst Hlth, Off Rare Dis, Natl Heart, Lung, & Blood Inst, Natl Inst Diabetes & Digest & Kidney, Genzyme DE thalassemia; nitric oxide; hemolysis; sickle cell disease ID SICKLE-CELL-DISEASE; ARGININE METABOLISM; ARGINASE ACTIVITY; NITRIC-OXIDE; SPLENECTOMIZED PATIENTS; ARTERIAL-HYPERTENSION; HYPERCOAGULABLE STATE; HEMOGLOBIN; ERYTHROCYTES; BIOAVAILABILITY AB Accumulating evidence supports the existence of a condition involving hemolysis-associated pulmonary hypertension (PHT). Hemolysis-induced release of cell-free hemoglobin and red blood cell arginase, resulting in impaired nitric oxide bioavailability, endothelial dysfunction, and PHT, has been reported in sickle cell disease. Since thalassemia is also a condition of chronic hemolysis, these patients are at risk. The data demonstrate that hemolysis-induced dysregulation of arginine metabolism and PHT also occurs in thalassemia. Erythrocyte release of arginase during hemolysis contributes to the development of PHT. Therapies that maximize arginine and nitric oxide bioavailability may benefit patients with thalassemia. C1 Childrens Hosp & Res Ctr Oakland, Dept Emergency Med, Oakland, CA 94609 USA. NHLBI, Crit Care Med Dept, Ctr Clin, NIH, Bethesda, MD 20824 USA. NHLBI, Cardiovasc Branch, Vasc Therapeut Sect, NIH, Bethesda, MD 20824 USA. Childrens Hosp & Res Ctr Oakland, Pediat Clin Res Ctr, Oakland, CA 94609 USA. Childrens Hosp & Res Ctr Oakland, Dept Hematol Oncol, Oakland, CA 94609 USA. RP Morris, CR (reprint author), Childrens Hosp & Res Ctr Oakland, Dept Emergency Med, 747 52nd St, Oakland, CA 94609 USA. EM claudiamorris@comcast.net RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU Intramural NIH HHS [Z99 HL999999, ZIA HL006014-02]; NCRR NIH HHS [M01 RR001271, M01-RR01271]; NHLBI NIH HHS [HL 7890, HL-04386-05, K23 HL004386, T35 HL007890] NR 30 TC 64 Z9 65 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 1-57331-580-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1054 BP 481 EP 485 DI 10.1196/annals.1345.058 PG 5 WC Hematology; Multidisciplinary Sciences SC Hematology; Science & Technology - Other Topics GA BDU40 UT WOS:000235427600058 PM 16339702 ER PT S AU Colby, CL Berman, RA Heiser, LM Saunders, RC AF Colby, CL Berman, RA Heiser, LM Saunders, RC BE Casagrande, VA Guillery, RW Sherman, SM TI Corollary discharge and spatial updating: when the brain is split, is space still unified? SO CORTICAL FUNCTION: A VIEW FROM THE THALAMUS SE Progress in Brain Research LA English DT Review CT Discussion Meeting on the Cortical Function - A View from the Thalamus CY SEP 12-14, 2004 CL Univ Wisconsin, Madison, WI HO Univ Wisconsin ID FRONTAL EYE FIELD; INFERIOR PARIETAL LOBULE; MONKEY SUPERIOR COLLICULUS; RHESUS-MONKEY; CORTICOCORTICAL COMMUNICATION; CORPUS-CALLOSUM; ANTERIOR COMMISSURE; VISUAL ACTIVATION; PULVINAR NEURONS; STEM TELLS AB How does the brain keep track of salient locations in the visual world when the eyes move? In parietal, frontal and extrastriate cortex, and in the superior colliculus, neurons update or 'remap' stimulus representations in conjunction with eye movements. This updating reflects a transfer of visual information, from neurons that encode a salient location before the saccade, to neurons that encode the location after the saccade. Copies of the oculomotor command - corollary discharge signals - must initiate this transfer. We investigated the circuitry that supports spacial updating in the primate brain. Our central hypothesis was that the forebrain commissures provide the primary route for remapping spatial locations across visual hemifields, from one cortical hemisphere to the other. Further, we hypothesized that these commissures provide the primary route for communicating corollary discharge signals from one hemisphere to the other. We tested these hypotheses using the double-step task and subsequent physiological recording in two split-brain monkeys. In the double-step task, monkeys made sequential saccades to two briefly presented targets, T1 and T2. In the visual version of the task, the representation of T2 was updated either within the same hemifield ("visual-within"), or across hemifields ("visual-across"). In the motor version, updating of the visual stimulus was always within-hemifield. The corollary discharge signal that initiated the updating, however, was generated either within the same hemisphere ("motor-within") or in the opposite hemisphere ("motor-across"). We expected that, in the absence of the forebrain commissures, both visual-across and motor-across conditions would be impaired relative to their "within" controls. In behavioral experiments, we observed striking initial impairments in the monkeys' ability to update stimuli across visual hemifields. Surprisingly, however, both animals were ultimately capable of performing the visual-across sequences of the double-step task. In subsequent physiological experiments, we found that neurons in lateral intraparietal cortex (LIP) can remap stimuli across visual hemifields, albeit with a reduction in the strength of remapping activity. These behavioral and neural findings indicate that the transfer of visual information is compromised, but by no means abolished, in the absence of the forebrain commissures. We found minimal evidence of impairment of the motor-across condition. Both monkeys readily performed the motor-across sequences of the doublestep task, and LIP neurons were robustly active when within-hemifield updating was initiated by a saccade into the opposite hemifield. These results indicate that corollary discharge signals are available bilaterally. Altogether, our findings show that both visual and corollary discharge signals from opposite hemispheres can converge to update spatial representations in the absence of the forebrain commissures. These investigations provide new evidence that a unified and stable representation of visual space is supported by a redundant circuit, comprised of cortical as well as subcortical pathways, with a remarkable capacity for reorganization. C1 Univ Pittsburgh, Dept Neurosci, Ctr Neural Basis Cognit, Mellon Inst, Pittsburgh, PA 15213 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Colby, CL (reprint author), Univ Pittsburgh, Dept Neurosci, Ctr Neural Basis Cognit, Mellon Inst, Room 115,4400 5th Ave, Pittsburgh, PA 15213 USA. EM ccolby@cnbc.cmu.edu NR 61 TC 19 Z9 19 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-51679-4 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2005 VL 149 BP 187 EP 205 DI 10.1016/S0079-6123(05)49014-7 PG 19 WC Neurosciences SC Neurosciences & Neurology GA BDA67 UT WOS:000232301900015 PM 16226585 ER PT S AU Wurtz, RH Sommer, MA Cavanaugh, J AF Wurtz, RH Sommer, MA Cavanaugh, J BE Casagrande, VA Guillery, RW Sherman, SM TI Drivers from the deep: the contribution of collicular input to thalamocortical processing SO CORTICAL FUNCTION: A VIEW FROM THE THALAMUS SE Progress in Brain Research LA English DT Review CT Discussion Meeting on the Cortical Function - A View from the Thalamus CY SEP 12-14, 2004 CL Univ Wisconsin, Madison, WI HO Univ Wisconsin ID SACCADIC EYE-MOVEMENTS; TEMPORAL VISUAL AREA; BRAIN-STEM TELLS; SUPERIOR COLLICULUS; CORTICOCORTICAL COMMUNICATION; FRONTAL-CORTEX; MONKEY; NUCLEUS; THALAMUS; ATTENTION AB A traditional view of the thalamus is that it is a relay station which receives sensory input and conveys this information to cortex. This sensory input determines most of the properties of first order thalamic neurons, and so is said to drive, rather than modulate, these neurons. This holds as a rule for first order thalamic nuclei, but in contrast, higher order thalamic nuclei receive much of their driver input back from cerebral cortex. In addition, higher order thalamic neurons receive inputs from subcortical movement-related centers. In the terminology popularized from studies of the sensory system, can we consider these ascending motor inputs to thalamus from subcortical structures to be modulators, subtly influencing the activity of their target neurons, or drivers, dictating the activity of their target neurons? This chapter summarizes relevant evidence front neuronal recording, inactivation, and stimulation of pathways projecting from the superior colliculus through thalamus to cerebral cortex. The study concludes that many inputs to the higher order nuclei of the thalamus from subcortical oculomotor areas - from the superior colliculus and probably other midbrain and pontine regions - should be regarded as motor drivers analogous to the sensory drivers at the first order thalamic nuclei. These motor drivers at the thalamus are viewed as being at the top of a series of feedback loops that provide information on impending actions, just as sensory drivers provide information about the external environment. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Wurtz, RH (reprint author), NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. EM bob@lsr.nei.nih.gov NR 44 TC 12 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-51679-4 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2005 VL 149 BP 207 EP 225 DI 10.1016/S0079-6123(05)49015-9 PG 19 WC Neurosciences SC Neurosciences & Neurology GA BDA67 UT WOS:000232301900016 PM 16226586 ER PT B AU Dufresee, CR Cutler, C Lee, JS Butman, J Fitzgibbon, EJ Kim, HJ Collins, MT AF Dufresee, C. R. Cutler, C. Lee, J. S. Butman, J. Fitzgibbon, E. J. Kim, H. J. Collins, M. T. BE David, DJ TI Surgical concerns in fibrous dysplasia and McCune-Albright Syndrome SO Craniofacial Surgery LA English DT Proceedings Paper CT 11th International Congress of the International-Society-of-Craniofacial-Surgery CY SEP 11-14, 2005 CL Coolum, AUSTRALIA SP Int Soc Cranio Surg C1 Georgetown Univ, NIH, INOVA Fairfax Hosp, Washington, DC 20057 USA. RP Dufresee, CR (reprint author), Georgetown Univ, NIH, INOVA Fairfax Hosp, Washington, DC 20057 USA. NR 0 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 88-7587-216-3 PY 2005 BP 81 EP 81 PG 1 WC Surgery SC Surgery GA BFO02 UT WOS:000243381600019 ER PT B AU Cutler, CM Kelly, MH Brillante, B Kim, JR Brewer, CC Zalewski, CK Lee, JS Butman, JA Fitzgibbon, EJ Robey, PG Dufresne, CR Collins, MT AF Cutler, C. M. Kelly, M. H. Brillante, B., Jr. Kim, J. R. Brewer, C. C. Zalewski, C. K. Lee, J. S. Butman, J. A. Fitzgibbon, E. J. Robey, P. G. Dufresne, C. R. Collins, M. T. BE David, DJ TI Characterization of the craniofacial effects of fibrous dysplasia and McCune-Albright syndrome SO Craniofacial Surgery LA English DT Proceedings Paper CT 11th International Congress of the International-Society-of-Craniofacial-Surgery CY SEP 11-14, 2005 CL Coolum, AUSTRALIA SP Int Soc Cranio Surg C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Sleletal Dis Branch, NIH, Bethesda, MD USA. RP Cutler, CM (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Sleletal Dis Branch, NIH, Bethesda, MD USA. NR 0 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 88-7587-216-3 PY 2005 BP 117 EP 119 PG 3 WC Surgery SC Surgery GA BFO02 UT WOS:000243381600029 ER PT J AU Hayes, LM AF Hayes, Lindsay M. TI Juvenile suicide in confinement in the United States: Results from a national survey SO CRISIS-THE JOURNAL OF CRISIS INTERVENTION AND SUICIDE PREVENTION LA English DT Article DE room confinement; training; suicide prevention policy components AB The first national study of juvenile suicide in confinement in the United States determined the extent and distribution of juvenile suicides (in juvenile detention centers, reception centers, and training schools); as well as gathered descriptive data on demographic characteristics of each victim, characteristics of the incident, and characteristics of the juvenile facility which sustained the suicide. Significant findings were found in the areas of time and location of the deaths, as well as adequacy of suicide prevention measures in facilities sustaining the deaths. C1 Natl Ctr Inst & Alternat, Mansfield, MA 02048 USA. RP Hayes, LM (reprint author), Natl Ctr Inst & Alternat, 40 Lantern Lane, Mansfield, MA 02048 USA. EM Lhayesta@msn.com NR 0 TC 11 Z9 11 U1 0 U2 1 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0227-5910 J9 CRISIS JI Crisis PY 2005 VL 26 IS 3 BP 146 EP 148 DI 10.1027/0227-5910.26.3.146 PG 3 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 204MM UT WOS:000249048100008 PM 16276758 ER PT J AU O'Grady, NP Dezfulian, C AF O'Grady, NP Dezfulian, C TI The femoral site as first choice for central venous access? Not so fast SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE central venous access; central venous catheters; bloodstream access; complications; catheter-related bloodstream infections; quality improvement ID CRITICALLY-ILL PATIENTS; CATHETER-RELATED INFECTIONS; THROMBOSIS; COMPLICATIONS; PREVENTION; MORTALITY; TRIAL; RISK C1 NIH, Bethesda, MD 20892 USA. RP O'Grady, NP (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. OI Dezfulian, Cameron/0000-0002-4486-0446 NR 14 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2005 VL 33 IS 1 BP 234 EP 235 DI 10.1097/01.CCM.0000150758.10396.F3 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 887WN UT WOS:000226336300037 PM 15644678 ER PT J AU Kagan, J Srivastava, S AF Kagan, J Srivastava, S TI Mitochondria as a target for early detection and diagnosis of cancer SO CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES LA English DT Review DE apoptosis; biomarker; diagnosis; differential expression; early detection; homoplasmicity; mitochondria; mitochondrion; mutation; prognosis; protein; proteome ID DIFFERENTIAL GEL-ELECTROPHORESIS; QUANTITATIVE PCR ANALYSIS; DOMINANT OPTIC ATROPHY; IRON-SULFUR CLUSTER; CODED AFFINITY TAGS; DNA MUTATIONS; CYTOCHROME-C; CELL-DEATH; MEMBRANE PERMEABILIZATION; PROTEOMICS APPROACH AB Mitochondrial dysfunction and mutations in mitochandrial DNA (mtDNA) have been frequently reported in cancer neurodegenerative diseases, diabetes, and aging syndromes. The mitochondrion genome (16.5 Kb) codes only for a small fraction (estimated to be 1%) of the proteins housed within this organelle. The other proteins are encoded by, the nuclear DNA (nDNA) and transported into the mitochondria. The identification of mitochondrial proteins that are aberrantly expressed in cancer cells and other diseases is now possible through recent developments in proteomic and bioinformatic technologies. These developments set the stage for a comprehensive organelle-based proteomic approach for the identification Of new markers for the early detection, risk assessment, and diagnosis of cancer, and other diseases and for the identification of new targets for therapeutic prevention and intervention. C1 NCI, Canc Biomarkers Res Grp, Div Canc Prevent, Rockville, MD 20852 USA. RP Kagan, J (reprint author), NCI, Canc Biomarkers Res Grp, Div Canc Prevent, 6130 Execut Blvd,Rm 3146, Rockville, MD 20852 USA. EM kaganj@mail.nih.gov NR 109 TC 16 Z9 18 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8363 J9 CRIT REV CL LAB SCI JI Crit. Rev. Clin. Lab. Sci. PY 2005 VL 42 IS 5-6 BP 453 EP 472 DI 10.1080/10408360500295477 PG 20 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 999YE UT WOS:000234427300002 PM 16390681 ER PT J AU Goggs, R Vaughan-Thomas, A Clegg, PD Carter, SD Innes, JF Mobasheri, A Shakibaei, M Schwab, W Bondy, CA AF Goggs, R Vaughan-Thomas, A Clegg, PD Carter, SD Innes, JF Mobasheri, A Shakibaei, M Schwab, W Bondy, CA TI Nutraceutical therapies for degenerative joint diseases: A critical review SO CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION LA English DT Review DE articular cartilage; essential fatty acids; glucosamine sulphate; glucose transport; nutraceutical; nutrition; osteoarthritis; osteochondritis; vitamin C ID N-3 FATTY-ACIDS; GREEN-LIPPED MUSSEL; FACTOR-KAPPA-B; ARTICULAR-CARTILAGE EXPLANTS; SUGAR/POLYOL TRANSPORT FACILITATORS; HUMAN OSTEOARTHRITIC CHONDROCYTES; QUINOLONE-INDUCED ARTHROPATHY; BLIND CLINICAL-EVALUATION; LIMITED FOOD-CONSUMPTION; GROWTH-PLATE CARTILAGE AB There is growing recognition of the importance of nutritional factors in the maintenance of bone and joint health, and that nutritional imbalance combined with endocrine abnormalities may be involved in the pathogenesis of osteoarthritis (OA) and osteochondritis dissecans (OCD). Despite this, dietary programs have played a secondary role in the management of these connective tissue disorders. Articular cartilage is critically dependent upon the regular provision of nutrients (glucose and amino acids), vitamins (particularly vitamin C), and essential trace elements (zinc, magnesium, and copper). Therefore, dietary supplementation programs and nutraceuticals used in conjunction with non-steroidal, anti- inflammatory drugs (NSAIDs) may offer significant benefits to patients with joint disorders, such as OA and OCD. This article examines the available clinical evidence for the efficacy of nutraceuticals, antioxidant vitamin C, polyphenols, essential fatty acids, and mineral cofactors in the treatment of OA and related joint disorders in humans and veterinary species. This article also attempts to clarify the current state of knowledge. It also highlights the need for additional targeted research to elucidate the changes in nutritional status and potential alterations to the expression of plasma membrane transport systems in synovial structures in pathophysiological states, so that current therapy and future treatments may be better focused. C1 Univ Liverpool, Fac Vet Sci, Connect Tissue Res Grp, Liverpool L69 7ZJ, Merseyside, England. Univ Munich, Inst Anat, Munich, Germany. Charite Med Univ Berlin, Inst Anat, Berlin, Germany. Tech Univ Dresden, Med Fac Carl Gustav Carus, Inst Anat, D-8027 Dresden, Germany. NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD USA. RP Mobasheri, A (reprint author), Univ Liverpool, Fac Vet Sci, Connect Tissue Res Grp, Liverpool L69 7ZJ, Merseyside, England. EM a.mobasheri@liverpool.ac.uk RI Carter, Stuart/D-9374-2013; OI Goggs, Robert/0000-0001-7446-6987; Innes, John/0000-0003-2758-3851; Carter, Stuart/0000-0002-3585-9400 NR 198 TC 39 Z9 44 U1 4 U2 17 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8398 J9 CRIT REV FOOD SCI JI Crit. Rev. Food Sci. Nutr. PY 2005 VL 45 IS 3 BP 145 EP 164 DI 10.1080/10408690590956341 PG 20 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 941IK UT WOS:000230208300001 PM 16048146 ER PT J AU Mor, G Romero, R Aldo, PB Abrahams, VM AF Mor, G Romero, R Aldo, PB Abrahams, VM TI Is the trophoblast an immune regulator?: The role of toll-like receptors during pregnancy SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Review DE TLR; trophoblast; pregnancy; immunology; implantation ID NATURAL-KILLER-CELLS; FEMALE REPRODUCTIVE-TRACT; INTRAUTERINE GROWTH RESTRICTION; LEUKOCYTE PROTEASE INHIBITOR; UTERINE EPITHELIAL-CELLS; NECROSIS-FACTOR-ALPHA; PRETERM DELIVERY; FAS LIGAND; INDUCED APOPTOSIS; CUTTING EDGE AB In the early 1950s, Medawar recognized for the first time the unique immunology of the maternal/fetal interface and its potential relevance for transplantation. In his original work, he described the "fetal allograft analogy" whereby the fetus may be viewed as a semi-allogeneic conceptus that has evaded rejection by the maternal immune system. Although numerous hypotheses have been proposed to prove this observation, none have demonstrated that the maternal immune system is antagonist to the invading trophoblast. In the present article, we have reviewed recent studies demonstrating the expression and function of Toll-like receptors (TLRs) in trophoblast cells, and, based on these data, we propose an alternative view for maternal/fetal immune interactions. C1 Yale Univ, Sch Med, Reprod Immunol Unit, Dept Obstet Gynecol & Reprod Sci, New Haven, CT 06520 USA. NICHD, Perinatol Res Branch, US Dept HHS, NIH, Bethesda, MD USA. NICHD, Perinatol Res Branch, US Dept HHS, NIH, Detroit, MI USA. RP Mor, G (reprint author), Yale Univ, Sch Med, Reprod Immunol Unit, Dept Obstet Gynecol & Reprod Sci, 333 Cedar St,FMB 301, New Haven, CT 06520 USA. EM Gil.Mor@yale.edu NR 108 TC 43 Z9 45 U1 0 U2 2 PU BEGELL HOUSE INC PI NEW YORK PA 145 MADISON AVE, STE 601, NEW YORK, NY 10016-7892 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2005 VL 25 IS 5 BP 375 EP 388 DI 10.1615/CritRevImmunol.v25.i5.30 PG 14 WC Immunology SC Immunology GA 971UX UT WOS:000232411400003 PM 16167887 ER PT J AU Webb, TJ Sumpter, TL Thiele, AT Swanson, KA Wilkes, DS AF Webb, TJ Sumpter, TL Thiele, AT Swanson, KA Wilkes, DS TI The phenotype and function of lung dendritic cells SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Review DE dendritic cells; lung; signaling; T cells; regulatory T cells ID REGULATORY T-CELLS; MHC CLASS-I; ANTIGEN-PRESENTING FUNCTION; TOLL-LIKE RECEPTORS; INDOLEAMINE 2,3-DIOXYGENASE EXPRESSION; EOSINOPHILIC AIRWAY INFLAMMATION; PERIPHERAL LYMPHOID ORGANS; NECROSIS-FACTOR-ALPHA; IFN-GAMMA PRODUCTION; LIGAND-TREATED MICE AB Dendritic cells (DCs) are central to the integration of innate and adaptive immunity. In contrast to B and T lymphocytes, DCs have retained many of the pattern recognition receptors and are thus uniquely able to sense stimuli such as tissue damage, necrosis, and bacterial and viral infection. Also, immature DCs respond to danger signals in the environment, which leads to their maturation, upon which DCs differentiate and acquire the ability to direct the development of the primary immune response. The ability of lung DCs to elicit specific CD4 and CD8 T lymphocyte responses have made them attractive targets for vaccine development strategies in the treatment and prevention of diseases such as allograft rejection responses, allergy, and asthma, as well as autoimmune disease and cancer. C1 Indiana Univ, Sch Med, Ctr Immunobiol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. NIH, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Wilkes, DS (reprint author), Indiana Univ, Sch Med, Ctr Immunobiol, Nuys Med Sci Bldg 224,635 Barnhill Dr, Indianapolis, IN 46202 USA. EM dwilkes@iupui.edu OI Webb, Tonya/0000-0003-3086-6414 FU NHLBI NIH HHS [HL/AI67177, HL60797, T32HL07910-02]; NIAID NIH HHS [T32AI060519] NR 246 TC 20 Z9 23 U1 0 U2 1 PU BEGELL HOUSE INC PI NEW YORK PA 145 MADISON AVE, STE 601, NEW YORK, NY 10016-7892 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2005 VL 25 IS 6 BP 465 EP 491 PG 27 WC Immunology SC Immunology GA 995GV UT WOS:000234089700002 PM 16390323 ER PT J AU Lee, CJ Lee, LH Gu, XX AF Lee, CJ Lee, LH Gu, XX TI Mucosal immunity induced by pneumococcal glycoconjugate SO CRITICAL REVIEWS IN MICROBIOLOGY LA English DT Review DE mucosal immunity; pneumococcal glycoconjugate; CpG adjuvant ID IMMUNODEFICIENCY-VIRUS TYPE-1; HEAT-LABILE ENTEROTOXIN; CPG DNA; INTRANASAL IMMUNIZATION; INTRAMUSCULAR IMMUNIZATION; VACCINE DEVELOPMENT; SYSTEMIC IMMUNITY; BACTERIAL TOXINS; SURFACE-ANTIGEN; IGA ANTIBODIES AB Host defenses against Streptococcus pneumoniae involve opsonophagocytosis mediated by antibodies and complement. Because the pneumococcus is a respiratory pathogen, mucosal immunity may play an important role in the defense against infection. The mechanism for protection in mucosal immunity consists of induction of immunity by the activation of lymphocytes within the mucosal-associated lymphoid tissues, transport of antigen-specific B and T cells from inductive sites through bloodstream and distribute to distant mucosal effector sites. Secretory IgA is primarily involved in protection of mucosal surfaces. Mucosal immunization is an effective way of inducing immune responses at mucosal surfaces. Several mucosal vaccines are in various stages of development. A number of mucosal adjuvants have been proposed. CpG oligodeoxynucleotide (ODN) has been shown to be an effective mucosal adjuvant for various antigens. Mucosal immunity induced by intranasal immunization was studied with a pneumococcal glycoconjugate, using CpG ODN as adjuvant. Mice immunized with type 9V polysaccharide (PS) conjugated to inactivated pneumolysin (Ply) plus CpG produced high levels of 9V PS IgG and IgA antibodies compared to the group that received the conjugate alone. High levels of subclasses of IgG1, IgG2 and IgG3 antibodies were also observed in sera of mice immunized with 9V PS-Ply plus CpG. In addition, high IgG and IgA antibody responses were observed in sera of young mice immunized with 9V PS-Ply plus CpG or the conjugate plus non-CpG compared with the group received the conjugate alone. These results reveal that mucosal immunization with pneumococcal glycoconjugate using CpG as adjuvant can confer protective immunity against pneumococcal infection. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD USA. RP Lee, CJ (reprint author), US FDA, Ctr Biol & Res, Rockville, MD 20852 USA. EM lee_chi@cber.fda.gov NR 65 TC 14 Z9 15 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-841X J9 CRIT REV MICROBIOL JI Crit. Rev. Microbiol. PY 2005 VL 31 IS 3 BP 137 EP 144 DI 10.1080/10408410591005093 PG 8 WC Microbiology SC Microbiology GA 956JY UT WOS:000231297200001 PM 16170904 ER PT J AU Fojo, T Farrell, N Ortuzar, W Tanimura, H Weinstein, J Myers, TG AF Fojo, T Farrell, N Ortuzar, W Tanimura, H Weinstein, J Myers, TG TI Identification of non-cross-resistant platinum compounds with novel cytotoxicity profiles using the NCI anticancer drug screen and clustered image map visualizations SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE platinum; drug discovery; drug screen; chemotherapy; bioinformatics; NCI-60; cisplatin; carboplatin; oxaliplatin ID METASTATIC COLORECTAL-CANCER; TUMOR-CELL-LINES; PHASE-II; MOLECULAR PHARMACOLOGY; ACQUIRED-RESISTANCE; OXALIPLATIN; CISPLATIN; OVARIAN; TRIAL; CIS-DICHLORODIAMMINEPLATINUM(II) AB The widespread clinical use of platinum compounds in cancer chemotherapy has prompted a search for new platinum agents. To search for platinum agents with novel profiles of activity, we used clustered image maps, the COMPARE algorithm, and other numerical methods to analyze platinum compounds submitted to the National Cancer Institute's anticancer drug screen and tested against the screen's 60 diverse human cancer cell lines (the NCI-60). A total of 107 platinum compounds for which the data were adequate could be clustered into 12 groups, 11 of which were characterized by distinctive activity profiles against the cell lines. Each group (except the mixed one) was then found to have a characteristic chemical structure as well. Four of the groups were subjected to further analysis. Mean graph representations of the averaged activity profiles of the different groups served to highlight their similarities and differences. To identify compounds that might retain activity in the setting of resistance to clinically used platinum compounds, we determined the activity levels of 38 of the compounds (representative of the different activity-structure groups) against cisplatin and oxaliplatin-resistant ovarian cancer cell lines. Many of the compounds retained activity against the resistant cells, providing evidence that they differ from cisplatin and oxaliplatin, not only in their selective activity against the various NCI-60 cell types, but are also in their susceptibility to mechanisms of resistance. Since platinum compounds have generally been classified as alkylating agents, we also compared their patterns of activity with those of representative alkylating agents, with NCI-60 growth rates, and with the profiles of 1582 molecular markers in the NCI-60 cells. Much more analysis remains to be done, but the absence of any definitive, biologically interpretable molecular predictor of activity is consistent with the idea that platinum compounds have multiple intracellular targets and that cells can have multiple mechanisms of resistance. (C) 2004 Published by Elsevier Ireland Ltd. C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, NIH, Mol Pharmacol Lab, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Dept Chem, Richmond, VA 23284 USA. NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA. RP Fojo, T (reprint author), NCI, Ctr Canc Res, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM tfojo@helix.nih.gov NR 36 TC 45 Z9 46 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD JAN PY 2005 VL 53 IS 1 BP 25 EP 34 DI 10.1016/j.critervone.2004.09.008 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 887WA UT WOS:000226335000004 PM 15607933 ER PT J AU Lizak, MJ Zigler, JS Bettelheim, FA AF Lizak, MJ Zigler, JS Bettelheim, FA TI Syneretic response to incremental pressures in calf lenses SO CURRENT EYE RESEARCH LA English DT Article DE calf lens; hydrostatic pressure; relaxographic imaging; syneretic response; T-1 and T-2 relaxation ID HUMAN CRYSTALLINE LENS; HUMAN-EYE; WATER; AGE; ACCOMMODATION; STATE; NMR AB Purpose: Syneretic response to pressure variation of 1 atm or more has been demonstrated previously in bovine and human lenses with nuclear magnetic resonance (NMR) relaxation measurements. This study is designed to prove that a similar response is observable in smaller pressure increments closer to the normal physiological range. Methods: Excised calf eyes were enucleated, the lenses dissected out, and immersed in medium. The lenses were exposed to incremental pressures ranging from 1 to 3 atm. At each pressure increment, a series of T-1-weighted and spin echo images were acquired. Each image was segmented into seven regions of interest and tabulated. Longitudinal (T-1) and transverse (T-2) relaxation times were calculated from numerical fits of the experimental values to a one-term exponential expression. Results: The relaxation parameters were obtained from fitting the image intensities to exponential equations, which yielded a relaxation time T and a pre-exponential factor M. The relaxation times and the pre-exponential terms of both parameters displayed linear dependence on pressure. There was no evidence of a threshold for syneretic response. Both T-1 and T-2 relaxation times decreased with increasing pressure. The pre-exponential term M-2 increased with pressure, whereas M-1 decreased with pressure; however, the slope of the latter was statistically not significantly different from zero. Concluslions: Syneretic response to pressure in calf lenses as determined by NMR relaxation measurements proved to be linearly dependent on pressure over a wide range of hydrostatic pressures. There was no range where the syneretic response was absent. These two findings allow the conclusion that the phenomenon observed hitherto at large pressure changes in vitro could be operative in vivo under physiological pressure changes during accommodation. C1 NINDS, MIF, NMR Imaging Res Facil, NIH, Bethesda, MD 20892 USA. NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. Adelphi Univ, Dept Chem, Garden City, NY 11530 USA. RP Lizak, MJ (reprint author), NINDS, MIF, NMR Imaging Res Facil, NIH, Bldg 10,Rm B1D69,9000 Rockville Pike, Bethesda, MD 20892 USA. EM lizakm@ninds.nih.gov NR 21 TC 3 Z9 3 U1 0 U2 1 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD JAN PY 2005 VL 30 IS 1 BP 21 EP 25 DI 10.1080/02713680490894216 PG 5 WC Ophthalmology SC Ophthalmology GA 899XX UT WOS:000227180200004 PM 15875361 ER PT J AU Hinnebusch, BJ AF Hinnebusch, BJ TI The evolution of flea-borne transmission in Yersinia pestis SO CURRENT ISSUES IN MOLECULAR BIOLOGY LA English DT Review ID STORAGE HMS(+) PHENOTYPE; PASTEURELLA-PESTIS; PHOSPHOLIPASE-D; MURINE TOXIN; XENOPSYLLA-CHEOPIS; FEEDING MECHANISM; GENETIC-ANALYSIS; STAPHYLOCOCCUS-EPIDERMIDIS; CAENORHABDITIS-ELEGANS; INTERCELLULAR-ADHESION AB Transmission by fleabite is a recent evolutionary adaptation that distinguishes Yersinia pestis, the agent of plague, from Yersinia pseudotuberculosis and all other enteric bacteria. The very close genetic relationship between Y. pestis and Y. pseudotuberculosis indicates that just a few discrete genetic changes were sufficient to give rise to fleaborne transmission. Y. pestis exhibits a distinct infection phenotype in its. ea vector, and a transmissible infection depends on genes that are specifically required in the. ea, but not the mammal. Transmission factors identified to date suggest that the rapid evolutionary transition of Y. pestis to flea-borne transmission within the last 1,500 to 20,000 years involved at least three steps: acquisition of the two Y. pestis-specific plasmids by horizontal gene transfer; and recruitment of endogenous chromosomal genes for new functions. Perhaps reflective of the recent adaptation, transmission of Y. pestis by fleas is inefficient, and this likely imposed selective pressure favoring the evolution of increased virulence in this pathogen. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Hinnebusch, BJ (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM jhinnebusch@niaid.nih.gov NR 118 TC 76 Z9 89 U1 5 U2 19 PU HORIZON SCIENTIFIC PRESS PI WYMONDHAM PA PO BOX 1, NORFOLK, WYMONDHAM NR18 0JA, ENGLAND SN 1467-3037 J9 CURR ISSUES MOL BIOL JI Curr. Issues Mol. Biol. PY 2005 VL 7 BP 197 EP 212 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 937RQ UT WOS:000229943600001 PM 16053250 ER PT J AU Pacher, P Obrosova, IG Mabley, JG Szabo, C AF Pacher, P Obrosova, IG Mabley, JG Szabo, C TI Role of nitrosative stress and peroxynitrite in the pathogenesis of diabetic complications. Emerging new therapeutical strategies SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE peroxynitrite; nitric oxide; superoxide; nitrotyrosine; diabetes; vascular; cardiomyopathy; nephropathy; neuropathy; retinopathy ID NITRIC-OXIDE SYNTHASE; PROTEIN-KINASE-C; POLY(ADP-RIBOSE) POLYMERASE ACTIVATION; ENDOTHELIUM-DEPENDENT VASODILATION; VASCULAR SUPEROXIDE-PRODUCTION; MYOFIBRILLAR CREATINE-KINASE; NERVE CONDUCTION-VELOCITY; RETRACTED ARTICLE. SEE; ENDONEURIAL BLOOD-FLOW; OXIDATIVE STRESS AB Macro- and microvascular disease are the most common causes of morbidity and mortality in patients with diabetes mellitus. Diabetic cardiovascular dysfunction represents a problem of great clinical importance underlying the development of various severe complications including retinopathy, nephropathy, neuropathy and increase the risk of stroke, hypertension and myocardial infarction. Hyperglycemic episodes, which complicate even well-controlled cases of diabetes, are closely associated with increased oxidative and, nitrosative stress, which can trigger the development of diabetic complications. Hyperglycemia stimulates the production of advanced glycosylated end products, activates protein kinase C, and enhances the polyol. pathway leading to increased superoxide anion formation. Superoxide anion interacts with nitric oxide, forming the potent cytotoxin peroxynitrite, which attacks various biomolecules in the vascular endothelium, vascular smooth muscle and myocardium, leading to cardiovascular dysfunction. The pathogenetic role of nitrosative stress and peroxynitrite, and downstream mechanisms including poly(ADP-ribose) polymerase (PARP) activation, is not limited to the diabetes-induced cardiovascular dysfunction, but also contributes to the development and progression of diabetic nephropathy, retinopathy and neuropathy. Accordingly, neutralization of peroxynitrite or pharmacological inhibition of PARP is a promising new approach in the therapy and prevention of diabetic complications. This review focuses on the role of nitrosative stress and downstream mechanisms including activation of PARP in diabetic complications and on novel emerging therapeutical strategies offered by neutralization of peroxynitrite and inhibition of PARP. C1 NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. Univ Brighton, Sch Pharm & Biomol Sci, Brighton, E Sussex, England. Inotek Pharmaceut, Beverly, MA 01915 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. Semmelweis Univ, Inst Human Physiol & Clin Expt Res, H-1085 Budapest, Hungary. RP Pacher, P (reprint author), NIAAA, Lab Physiol Studies, NIH, 5625 Fishers Lane MSC 9413,Room 2S24, Bethesda, MD 20892 USA. EM ppacher@lycos.com RI Mabley, Jon/D-2296-2010; Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU Intramural NIH HHS [Z01 AA000375-02] NR 106 TC 191 Z9 204 U1 0 U2 12 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PY 2005 VL 12 IS 3 BP 267 EP 275 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 897IM UT WOS:000226997300002 PM 15723618 ER PT J AU Calzada, MJ Roberts, DD AF Calzada, MJ Roberts, DD TI Novel integrin antagonists derived from thrombospondins SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE angiogenesis; cell motility inhibitors; peptides; cell adhesion; antiproliferative peptides; peptide mimetics; integrins ID ENDOTHELIAL-CELL PROLIFERATION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; BREAST-CARCINOMA CELLS; IMMEDIATE-EARLY GENE; LEUKOCYTE ADHESION MOLECULE-1; HUMANIZED MONOCLONAL-ANTIBODY; HEPARAN-SULFATE PROTEOGLYCANS; AMINO-ACID SUBSTITUTIONS; TERMINAL GLOBULAR DOMAIN; HUMAN SKIN FIBROBLASTS AB Specific antagonists have been Successfully developed for several different integrins. Clinical trials have been initiated to study therapeutic uses of these inhibitors in cancer, thrombosis, and inflammatory diseases. Most efforts to date have focused on the platelet integrin alphaIIbbeta3, endothelial alphavbeta3, and the leukocyte integrin alpha4beta1. However, the integrin family contains additional members with interesting tissue specificities and functional properties that could also be useful molecular targets for disease intervention. In many cases, specific recognition motifs for these integrins have not been identified, which has precluded development or specific antagonists. Our recent studies of thrombospondin-1 and thrombospondin-2 recognition by integrins have revealed novel motifs for alpha3beta1 and alpha6beta1 integrins as well as new motifs recognized by the well studied alpha4beta1 integrin. These three integrins play distinct roles in angiogenesis and its modulation by thrombospondins. This review will discuss recent insights into the specificities of alpha3beta1 and alpha6beta1 integrins, their functions in angiogenesis, and potential applications for antagonists of these integrins and of alpha4beta1 to control pathological angiogenesis and other diseases. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Roberts, DD (reprint author), Bldg 10,Room 2A33,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 229 TC 17 Z9 18 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2005 VL 11 IS 7 BP 849 EP 866 DI 10.2174/1381612053381792 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 899RH UT WOS:000227162000005 PM 15777239 ER PT J AU Alper, O Bowden, ET AF Alper, O Bowden, ET TI Novel insights into c-Src SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE c-Src; v-Src; tumorigenesis; angiogenesis; genomics ID FOCAL ADHESION KINASE; HEPATOCYTE GROWTH-FACTOR; PROTEIN-TYROSINE KINASES; TYPE-1 MATRIX-METALLOPROTEINASE; THROMBIN-STIMULATED PLATELETS; MAMMARY EPITHELIAL-CELLS; FAMILY KINASES; ESTROGEN-RECEPTOR; BREAST-CARCINOMA; DOWN-REGULATION AB Since identifying a transmissible agent responsible for tumorigenesis in chickens, the v-Src oncogene, significant progress has been made in determining the functions of its cellular homologue. c-Src is the product of the SRC gene and has been found both over-expressed and highly activated in a number of human cancers. In fact the relationship between c-Src activation and cancer progression is significant. Furthermore. c-Src may play a role in the acquisition of the invasive and metastatic phenotype. In this review we will summarize some of the latest evidence for the role of c-Src in tumorigenesis and particularly in human tumor progression. In this review, specifically, we will address growth signals, adhesion, migration, invasion, angiogenesis and functional genomics. C1 Natl Inst Neurol Disorders, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Vincent T Lombardi Canc Res Ctr, Dept Oncol, Washington, DC USA. RP Alper, O (reprint author), Natl Inst Neurol Disorders, NIH, Bldg 10,Rm 5D37, Bethesda, MD 20892 USA. EM alpero@mail.nih.gov NR 156 TC 36 Z9 37 U1 2 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2005 VL 11 IS 9 BP 1119 EP 1130 DI 10.2174/1381612053507576 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 906SW UT WOS:000227664400005 PM 15853660 ER PT J AU Lee, Y Rodriguez, C Dionne, RA AF Lee, Y Rodriguez, C Dionne, RA TI The role of COX-2 in acute pain and the use of selective COX-2 inhibitors for acute pain relief SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE cyclooxygenase-1; cyclooxygenase-2; non-steroidal anti-inflammatory drugs; selective cyclooxygenase-2 inhibitors; prostaglandins; acute pain; oral surgery model ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ENDOPEROXIDE-H SYNTHASE-1; PROSTAGLANDIN-E SYNTHASE; RAT SPINAL-CORD; CYCLOOXYGENASE-2 MESSENGER-RNA; CYTOSOLIC PHOSPHOLIPASE A(2); PERIPHERAL PROSTANOID LEVELS; RANDOMIZED CONTROLLED-TRIAL; POSTOPERATIVE DENTAL PAIN; ORAL-SURGERY MODEL AB Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of therapy for the management of acute pain. Cyclooxygenase (COX) enzyme is of particular interest because it is the major target of NSAIDs. Although NSAIDs are remarkably effective in the management of pain and inflammation, their use is limited by several adverse effects including gastrointestinal bleeding and ulceration, impaired renal function, and inhibition of platelet aggregation. Discovery of a second cyclooxygenase, COX-2, led to the hypothesis that NSAID side effects could be decreased, as the inhibition of COX-2 is more directly implicated in ameliorating inflammation while the inhibition of COX-1 is related to adverse effects in the GI tract. This stimulated the development of selective COX-2 inhibitors (coxibs) that are better tolerated than nonselective NSAIDs but comparable in analgesic efficacy. This article provides an overview on the therapeutic use of selective COX-2 inhibitors for relief of acute pain, largely based on clinical trials in patients undergoing the surgical removal of impacted third molars, with focus on analgesic efficacy and the potential safety associated with their use compared to dual COX-1/COX-2 inhibitors. C1 Natl Inst Dent & Craniofacial Res, Pain & Neurosurg Mechanisms Branch, NIH, Bethesda, MD 20892 USA. Boston Univ, Goldman Sch Dent Med, Dept Endodont, Boston, MA 02215 USA. RP Dionne, RA (reprint author), Natl Inst Dent & Craniofacial Res, Pain & Neurosurg Mechanisms Branch, NIH, Bldg 10,Rm 1N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM rdionne@dir.nidcr.nih.gov NR 115 TC 25 Z9 27 U1 0 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2005 VL 11 IS 14 BP 1737 EP 1755 DI 10.2174/1381612053764896 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 923LX UT WOS:000228912500002 PM 15892672 ER PT J AU Mahady, GB AF Mahady, GB TI Medicinal plants for the prevention and treatment of bacterial infections SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE antibacterial; antiadhesive; botanicals; infectious disease; medicinal plants; multidrug resistant pumps; traditional medicine ID RESISTANT STAPHYLOCOCCUS-AUREUS; HELICOBACTER-PYLORI INFECTION; FIMBRIATED ESCHERICHIA-COLI; IN-VITRO SUSCEPTIBILITY; TEA TREE OIL; MONGOLIAN GERBILS; ANTIBACTERIAL ACTIVITY; MELALEUCA-ALTERNIFOLIA; ANTIMICROBIAL ACTIVITY; STREPTOCOCCAL INFECTIONS AB Infectious diseases are a significant cause of morbidity and mortality worldwide, accounting for approximately 50% of all deaths in tropical countries and as much as 20% of deaths in the Americas. Despite the significant progress made in microbiology and the control of microorganisms, sporadic incidents of epidemics due to drug resistant microorganisms and hitherto unknown disease-causing microbes pose an enormous threat to public health. These negative health trends call for a global initiative for the development of new strategies for the prevention and treatment of infectious disease. For over 100 years chemical compounds isolated from medicinal plants have served as the models for many clinically proven drugs, and are now being re-assessed as antimicrobial agents. The reasons for this renaissance include a reduction in the new antibacterial drugs in the pharmaceutical pipeline, an increase in antimicrobial resistance, and the need of treatments for new emerging pathogens. Literally thousands of plant species have been tested against hundreds of bacterial strains in vitro and many medicinal plants are active against a wide range of gram positive and gram negative bacteria. However, very few of these medicinal plant extracts have been tested in animal or human studies to determine safety and efficacy. This review focuses on the medicinal plants and bacteria for which there is significant published in vitro, in vivo and clinical data available. The examples provided in this review indicate that medicinal plants offer significant potential for the development of novel antibacterial therapies and adjunct treatments (i.e. MDR pump inhibitors). C1 Univ Illinois, Coll Pharm, Dept Pharm Practice,Collaborating Ctr Tradit Med, Dept Med Chem & Pharmacognosy,WHO, Chicago, IL 60612 USA. RP Mahady, GB (reprint author), Univ Illinois, Coll Pharm, NIH, Bot Ctr Dietary Supplements, 833 S Wood St,MC 877, Chicago, IL 60612 USA. EM mahady@uic.edu FU NCCIH NIH HHS [R21 AT000412-02] NR 121 TC 54 Z9 56 U1 2 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2005 VL 11 IS 19 BP 2405 EP 2427 DI 10.2174/1381612054367481 PG 23 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 935ET UT WOS:000229763100002 PM 16026296 ER PT J AU Suh, KS Yuspa, SH AF Suh, KS Yuspa, SH TI Intracellular chloride channels: Critical mediators of cell viability and potential targets for cancer therapy SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE chloride channel; CFTR; CIC; CLIC; CLCA; cancer therapy; apoptosis; cell cycle ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CYCLE-DEPENDENT EXPRESSION; NECROSIS-FACTOR-ALPHA; HUMAN BREAST-CANCER; ION-CHANNEL; CYSTIC-FIBROSIS; ANION CHANNEL; CYCLOPRODIGIOSIN HYDROCHLORIDE; SUBCELLULAR-DISTRIBUTION; FUNCTIONAL EXPRESSION AB The passage of ions to form and maintain electrochemical gradients is a key element for regulating cellular activities and is dependent on specific channel proteins or complexes. Certain ion channels have been the targets of pharmaceuticals that have had impact on a variety of cardiovascular and neurological diseases. Chloride channels regulate the movement of a major cellular anion, and in so doing they in part determine cell membrane potential, modify transepithelial transport, and maintain intracellular pH and cell volume. There are multiple families of chloride channel proteins, and respiratory, neuromuscular, and renal dysfunction may result from mutations in specific family members. Interest in chloride channels related to cancer first arose when the multidrug resistance protein (MDR/P-glycoprotein) was linked to volume-activated chloride channel activity in cancer cells from patients undergoing chemotherapy. More recently. CLC. CLIC, and CLCA intracellular chloride channels have been recognized for their contributions in modifying cell cycle, apoptosis, cell adhesion, and cell motility. Moreover, advances in structural biology and high-throughput screening provide a platform to identify chemical compounds that modulate the activities of intracellular chloride channels thereby influencing chloride ion transport and altering cell behavior. This review will focus on several chloride channel families that may contribute to the cancer phenotype and suggest how they may serve as novel targets for primary cancer therapy. C1 NCI, Lab Cellular Carcinogenesis & Tumor Promot, Canc Res Ctr, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), NCI, Lab Cellular Carcinogenesis & Tumor Promot, Canc Res Ctr, Bethesda, MD 20892 USA. EM yuspas@dc37a.nci.nih.gov NR 108 TC 33 Z9 33 U1 0 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2005 VL 11 IS 21 BP 2753 EP 2764 DI 10.2174/1381612054546806 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 946ZB UT WOS:000230610700007 PM 16101453 ER PT J AU Cho-Chung, YS AF Cho-Chung, YS TI DNA drug design for cancer therapy SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE antisense; oligonucleotides; DNA drugs; gene expression; cancer; growth inhibition; transcription factor decoy ID PROTEIN-KINASE-A; ENDOTHELIAL GROWTH-FACTOR; RI-ALPHA SUBUNIT; VASCULAR-PERMEABILITY FACTOR; TRANSCRIPTION FACTOR DECOY; C-RAF KINASE; NF-KAPPA-B; ANTISENSE OLIGODEOXYNUCLEOTIDES ENHANCE; MIXED-BACKBONE OLIGONUCLEOTIDES; SERINE THREONINE KINASES AB DNA (antisense and other oligonucleotides) drug design represents a direct genetic approach for cancer treatment. Such an approach takes advantage of mechanisms that activate genes known to confer a growth advantage to neoplastic cells. The ability to block the expression of these genes allows exploration of normal growth regulation. Progress in DNA drug technology has been rapid, and the traditional antisense inhibition of gene expression is now viewed on a genomic scale. This global view has led to a new vision in antisense technology, the elimination of nonspecific and undesirable side effects, and ultimately the generation of more effective and less toxic nucleic acid medicines. Several antisense oligonucleotides are in clinical trials, are well tolerated, and are potentially active therapeutically. DNA drugs are promising molecular medicines for treating human cancer in the near future. C1 NCI, CCR, BRL, Cellular Biochem Sect, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, CCR, BRL, Cellular Biochem Sect, Bldg 10,Rm 5B05,9000 Rockville Pike, Bethesda, MD 20892 USA. EM yc12b@nih.gov FU NCI NIH HHS [N01-BC76212/C2700212] NR 188 TC 7 Z9 7 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2005 VL 11 IS 22 BP 2811 EP 2823 DI 10.2174/1381612054546770 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 946ZC UT WOS:000230610800002 PM 16101439 ER PT J AU Pommier, Y Sordet, O Rao, VA Zhang, HL Kohn, KW AF Pommier, Y Sordet, O Rao, VA Zhang, HL Kohn, KW TI Targeting Chk2 kinase: Molecular interaction maps and therapeutic rationale SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE cell cycle checkpoints; apoptosis; DNA double-strand breaks; DNA repair ID DNA-DAMAGE CHECKPOINT; S-PHASE CHECKPOINT; DOUBLE-STRAND BREAKS; CELL-CYCLE ARREST; ATM-DEPENDENT PHOSPHORYLATION; TELANGIECTASIA-MUTATED ATM; LI-FRAUMENI-SYNDROME; POLO-LIKE KINASE-1; ATAXIA-TELANGIECTASIA; IONIZING-RADIATION AB Most anticancer drugs presently used clinically target genomic DNA. The selectivity of these anticancer drugs for tumor tissues is probably due to tumor-specific defects suppressing cell cycle checkpoints and DNA repair, and enhancing apoptotic response in the tumor. We will review the molecular interactions within the ATM-Chk2 pathway implicating the DNA damage sensor kinases (ATM, ATR and DNA-PK), the adaptor BRCT proteins (Nbs1, Brca1, 53BP1 MDC1) and the effector kinases (Chk2, Chk1, Plk3, JNK.. p38). The molecular interaction map convention (MIM) will be used for presenting this molecular network (http://discover.nci.nih.gov/mim/). A characteristic of the ATM-Chk2 pathway is its redundancy. First, ATM and Chk2 phosphorylate common substrates including p53, E2F1, BRCA1, and Chk2 itself, which suggests that Chk2 (also known as CHECK2, Cds1 in fission yeast, and Dmchk2 or Dmnk or Loki in the fruit fly) acts as a relay for ATM and/or as a salvage pathway when ATM is inactivated. Secondly, redundancy is apparent for the substrates, which can be phosphorylated/activated at similar residues by Chk2, Chk1, and the polo kinases (Plk's). Functionally, Chk2 can activate both apoptosis (via p53, E2F1 and PML) and cell cycle checkpoint (via Cdc25A and Cdc25C, p53, and BRCA1). We will review the short list of published Chk2 inhibitors. We will also propose a novel paradigm for screening interfacial inhibitors of Chk2. Chk2 inhibitors might be used to enhance the tumor selectivity of DNA targeted agents in p53-deficient tumors, and for the treatment of tumors whose growth depends on enhanced Chk2 activity. C1 NIH, Mol Pharmacol Lab, Ctr Canc Res, Natl Canc Inst,DHHS, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NIH, Mol Pharmacol Lab, Ctr Canc Res, Natl Canc Inst,DHHS, Bldg 37,Room 5068, Bethesda, MD 20892 USA. EM Pommier@nih.gov RI Sordet, Olivier/M-3271-2014 NR 224 TC 62 Z9 65 U1 1 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2005 VL 11 IS 22 BP 2855 EP 2872 DI 10.2174/1381612054546716 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 946ZC UT WOS:000230610800005 PM 16101442 ER PT J AU St Georgiev, V AF St Georgiev, V TI Treatment of infectious diseases and drug resistance SO CURRENT PHARMACEUTICAL DESIGN LA English DT Editorial Material ID ANTIRETROVIRAL DRUGS; ENTEROCOCCI C1 NIAID, NIH, Bethesda, MD 20892 USA. RP St Georgiev, V (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. EM vgeorgiev@niaid.nih.gov NR 20 TC 0 Z9 0 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2005 VL 11 IS 24 BP 3073 EP 3075 DI 10.2174/1381612054864966 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 955MJ UT WOS:000231229700001 ER PT J AU Woodard, GE Rosado, JA AF Woodard, GE Rosado, JA TI G-protein coupled receptors and calcium signaling in development SO CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY, VOL 65 SE CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY LA English DT Review ID PANCREATIC ACINAR-CELLS; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; MEDIATED CA2+ ENTRY; CYCLIC ADP-RIBOSE; ADENINE-DINUCLEOTIDE PHOSPHATE; DEPENDENT NA+/CA2+ EXCHANGER; BETA-ADRENERGIC-RECEPTOR; HUMAN PLATELETS; ENDOPLASMIC-RETICULUM; ACTIN CYTOSKELETON C1 NIDDKD, Metab Dis Branch, Bethesda, MD 20892 USA. Univ Extremadura, Dept Physiol, Caceres 10071, Spain. RP Woodard, GE (reprint author), NIDDKD, Metab Dis Branch, Bethesda, MD 20892 USA. RI Woodard, Geoffrey/A-8608-2009; rosado, juan/H-3488-2015 OI rosado, juan/0000-0002-9749-2325 NR 129 TC 2 Z9 3 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 J9 CURR TOP DEV BIOL PY 2005 VL 65 BP 189 EP 210 PG 22 WC Developmental Biology SC Developmental Biology GA BBY01 UT WOS:000228295600007 PM 15642384 ER PT S AU Bianco, C Strizzi, L Normanno, N Khan, N Salomon, DS AF Bianco, C Strizzi, L Normanno, N Khan, N Salomon, DS BE Schatten, GP TI Cripto-1: An oncofetal gene with many faces SO CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY, VOL 67 SE Current Topics in Developmental Biology LA English DT Review ID MAMMARY EPITHELIAL-CELLS; GROWTH-FACTOR-RECEPTOR; EMBRYONIC STEM-CELLS; BREAST-CANCER CELLS; FACTOR-RELATED PROTEINS; ONE-EYED-PINHEAD; LEFT-RIGHT AXIS; EGF-CFC FAMILY; DIFFERENTIAL IMMUNOHISTOCHEMICAL DETECTION; CERVICAL-CARCINOMA CELLS AB Human Cripto-1 (CR-1), a member of the epidermal growth factor (EGF)-CFC family, has been implicated in embryogenesis and in carcinogenesis. During early vertebrate development, CR-1 functions as a co-receptor for Nodal, a transforming growth factor beta (TGF beta) family member and is essential for mesoderm and endoderm formation and anterior-posterior and left-right axis establishment. In adult tissues, CR-1 is expressed at a low level in all stages of mammary gland development and expression increases during pregnancy and lactation. Overexpression of CR-1 in mouse mammary epithelial cells leads to their transformation in vitro and, when injected into mammary glands, produces ductal hyperplasias. CR-1 can also enhance migration, invasion, branching morphogenesis and epithelial to mesenchymal transition (EMT) of several mouse mammary epithelial cell lines. Furthermore, transgenic mouse studies have shown that overexpression of a human CR-1 transgene in the mammary gland under the transcriptional control of the mouse mammary tumor virus (MMTV) promoter results in mammary hyperplasias and papillary adenocarcinomas. Finally, CR-1 is expressed at high levels in approximately 50 to 80% of different types of human carcinomas, including breast, cervix, colon, stomach, pancreas, lung, ovary, and testis. In conclusion, EGF-CFC proteins play dual roles as embryonic pattern formation genes and as oncogenes. While during embryogenesis EGF-CFC proteins perform specific and regulatory functions related to cell and tissue patterning, inappropriate expression of these molecules in adult tissues can lead to cellular proliferation and transformation and therefore may be important in the etiology and/or progression of cancer. (c) 2005, Elsevier Inc. C1 NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. ITN Fdn Pascale, Div Haematol Oncol, I-80131 Naples, Italy. ITN Fdn Pascale, Dept Expt Oncol, I-80131 Naples, Italy. RP Bianco, C (reprint author), NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. OI Normanno, Nicola/0000-0002-7158-2605 NR 214 TC 46 Z9 47 U1 3 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 BN 0-12-153167-8 J9 CURR TOP DEV BIOL JI Curr. Top. Dev. Biol. PY 2005 VL 67 BP 85 EP 133 DI 10.1016/S0070-2153(05)67003-2 PG 49 WC Developmental Biology SC Developmental Biology GA BCM26 UT WOS:000229969000003 PM 15949532 ER PT S AU Sonoyama, W Coppe, C Gronthos, S Shi, ST AF Sonoyama, W Coppe, C Gronthos, S Shi, ST BE Schatten, GP TI Skeletal stem cells in regenerative medicine SO CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY, VOL 67 SE Current Topics in Developmental Biology LA English DT Review ID HUMAN-BONE-MARROW; MESENCHYMAL PROGENITOR CELLS; UMBILICAL-CORD BLOOD; DIFFUSION-CHAMBERS INVIVO; DIFFERENTIATION IN-VITRO; COLONY-FORMING CELLS; HUMAN ADIPOSE-TISSUE; STROMAL CELLS; OSTEOGENESIS IMPERFECTA; ENDOTHELIAL-CELLS AB Postnatal stem cells have been isolated from a variety of tissues and they are highly expected to have potentiality to be utilized for cell-based clinical therapies. Bone marrow stromal stem cells (BMSSCs) derived from bone marrow stromal tissue have been identified as a population of multipotent mesenchymal stem cells that are capable of differentiating into osteoblasts, adipocytes, chondrocytes, muscle cells, and neural cells. The most significant tissue regeneration trait of BMSSCs is their in vivo bone regeneration capability, which has been widely studied for understanding molecular and cellular mechanisms of osteogenesis, and, more importantly, developing into a stem-cell-based therapy. Recent studies further demonstrated that BMSSC-mediated bone regeneration is a promising approach for regenerative medicine in clinical trials. However, there are some fundamental questions that remain to be answered prior to successful utilization of BMSSCs in clinical therapy. For instance, how to maintain sternness of BMSSCs will be a critical issue for developing methodologies to propagate multi-potential stem cells in vitro, in order to allow the development of effective clinical therapies. (c) 2005, Elsevier Inc. C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. Inst Med & Vet Sci, Mesenchymal Stem Cell Grp, Div Haematol, Adelaide, SA 5000, Australia. RP Sonoyama, W (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. NR 121 TC 5 Z9 5 U1 1 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 BN 0-12-153167-8 J9 CURR TOP DEV BIOL JI Curr. Top. Dev. Biol. PY 2005 VL 67 BP 305 EP 323 DI 10.1016/S0070-2153(05)67010-X PG 19 WC Developmental Biology SC Developmental Biology GA BCM26 UT WOS:000229969000010 PM 15949539 ER PT S AU Wu, CY Pike, VW Wang, YM AF Wu, CY Pike, VW Wang, YM BE Ahrens, ET TI Amyloid imaging: From benchtop to bedside SO CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY, VOLUME 70 SE Current Topics in Developmental Biology LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; BLOOD-BRAIN-BARRIER; ALZHEIMERS-DISEASE BRAIN; REPORTER GENE-EXPRESSION; IN-VIVO DETECTION; MONOCLONAL-ANTIBODY; CONGO RED; P COMPONENT; BETA-PEPTIDE; THIOFLAVIN-T AB Tremendous efforts have been made in the search for a cure or effective treatment of Alzheimer's disease (AD) to develop therapies aimed at halting or reversing amyloid plaque deposition in the brain. This necessitates in vivo detection and quantification of amyloid plaques in the brain for efficacy evaluation of anti-amyloid therapies. For this purpose, a wide array of amyloid-imaging probes has been developed, mainly for in vivo studies based on positron emission tomography and single photon emission computed tomography. This review provides a full account of the development of amyloid-imaging agents. The in vitro binding properties and in vivo pharmacokinetic profiles of all amyloid-imaging agents so far reported are comprehensively and uniquely surveyed. Emphasis is placed on the development of small-molecule probes based on amylold dyes, such as Congo red and thioflavin T. Compared to large biomolecules, these small-molecule probes have been systematically investigated through extensive structure activity relationship studies. Many of the probes show favorable properties for in vivo studies. As a result, three lead compounds, termed PIB (Pittsburgh-Compound B, [C-11]6-OH-BTA-1), FDDNP (2-(1-[6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene) malononitrile), and SB-13 (4-N-methylamino-4'-hydroxystilbene), have been identified and evaluated in human subjects. Preliminary studies have indicated that these lead compounds exhibit a characteristic retention in AD subjects that is consistent with the AD pathology, thus proving the concept that amyloid deposits in the brain can be readily detected and quantified in vivo. The progress to date paves the way for further investigation in various aspects of AD research. Once developed, these amyloid-imaging agents could be used as biomarkers to aid in early and definitive diagnosis of AD, facilitate drug discovery and development, and allow pathophysiological studies of the disease mechanism. Furthermore, the success in the development of amyloid-imaging agents helps with the development of imaging agents for in vivo studies of other AD pathologies in particular and of neurodegenerative disorders in general. (c) 2005, Elsevier Inc. C1 Univ Illinois, Coll Pharm, Dept Med Chem, Chicago, IL 60612 USA. Jiangsu Inst Nucl Med, Natl Lab Nucl Med, Jiangsu 214063, Peoples R China. NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Wu, CY (reprint author), Univ Illinois, Coll Pharm, Dept Med Chem, Chicago, IL 60612 USA. FU NIA NIH HHS [AG 22048] NR 134 TC 30 Z9 32 U1 2 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 BN 0-12-153170-8 J9 CURR TOP DEV BIOL JI Curr. Top. Dev. Biol. PY 2005 VL 70 BP 171 EP + DI 10.1016/S0070-2153(05)70008-9 PG 45 WC Developmental Biology SC Developmental Biology GA BDK76 UT WOS:000234003500008 PM 16338342 ER PT J AU Keefer, LK AF Keefer, LK TI Nitric oxide (NO)- and nitroxyl (HNO)-generating diazeniumdiolates (NONOates): Emerging commercial opportunities SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review ID SELECTIVE PULMONARY VASODILATION; EXPERIMENTAL CEREBRAL VASOSPASM; CONTROLLED-RELEASE POLYMER; MUSCLE CELL-PROLIFERATION; IN-VIVO EVALUATION; NO DONOR; SOL-GELS; JS-K; LUNG INJURY; INDUCED HEPATOTOXICITY AB Diazeniumdiolate ions are convenient and, for a variety of applications, uniquely advantageous nitric oxide (NO) dosage forms. Ionic diazeniumcliolates generate bioactive NO in physiological fluids truly spontaneously (i. e., without metabolism or redox activation), with reliable half-lives ranging from 2 seconds to 20 hours depending on the ion's structure. They are generally simple-to-prepare solids with excellent shelf life and high NO content - up to 40% by weight. Very importantly from the pharmaceutical point of view, the ionic diazeniumcliolates can be easily derivatized to prodrug forms that can be activated for NO release enzymatically, photolytically, or by slowed hydrolysis, allowing for rational design of strategies for targeting pharmacological delivery of NO to sites of need Without unwanted collateral exposure of other NO-sensitive compartments. In addition to their world-wide sale for use in probing the chemical biology of NO, published proof-of-concept studies with diazeniumcliolates suggest several more lucrative applications. These include: converting existing drugs and biologicals to NO-releasing form to improve performance and/or extend patent life; diazeniumcliolating medical devices for improved biocompatibility; anticancer drug discovery; use as surgical aids and for wound repair; field generation of NO gas; and nonmedical uses such as extending the post-harvest life of cut flowers. Future work aimed at exploiting the full clinical potential of diazeniumdiolate technology will be pursued in this laboratory and strongly encouraged in others, with a concurrent fundamental research effort to broaden the knowledge base from which further opportunities can be inferred [e. g., exploiting the very recent finding that some diazeniumdiolates appear to offer a versatile platform from which nitroxyl (HNO)-generating prodrugs can be developed]. C1 NCI, Frederick, MD 21702 USA. RP Keefer, LK (reprint author), NCI, Bldg 538, Frederick, MD 21702 USA. EM keefer@ncifcrf.gov RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 96 TC 69 Z9 75 U1 1 U2 22 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 EI 1873-4294 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2005 VL 5 IS 7 BP 625 EP 634 DI 10.2174/1568026054679380 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 957OR UT WOS:000231380300004 PM 16101424 ER PT J AU Joshi, BV Jacobson, KA AF Joshi, BV Jacobson, KA TI Purine derivatives as ligands for A(3) adenosine receptors SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE agonist; antagonist; purine; 7TM receptor; tissue protection; radioligand ID MOUSE INTRAOCULAR-PRESSURE; HIGH-AFFINITY RADIOLIGAND; HIGHLY POTENT; STRUCTURAL DETERMINANTS; ADENINE NUCLEOSIDES; SELECTIVE AGONISTS; MOLECULAR-CLONING; A-3 RECEPTOR; BINDING-SITE; MAST-CELL AB Selective agonists and antagonists for A(3) adenosine receptors (ARs) are being explored for the treatment of a variety of disorders, including brain and heart ischemic conditions, cancer, and rheumatoid arthritis. This review covers both the structure activity relationships of nucleoside agonist ligands and selected antagonists acting at this receptor and the routes of synthesis. Highly selective agonists have been designed, using both empirical approaches and. semi-rational approach based on molecular modeling. The prototypical A(3) agonists 1B-MECA 10 and the more receptor-subtypeselective Cl-IB-MECA 11, both of which have affinity in binding to the receptor of similar to 1 nM, have been used widely as pharmacological probes in the elucidation of the physiological role of this receptor. In addition to the exploration of the effects of structural modification of the adenine and ribose moieties on A(3)AR affinity, the effects of these structural changes on the intrinsic efficacy have also been studied in a systematic fashion. Key structural features determining A3AR interaction include the N-6-benzyl group, 2-position substitution such as halo, substitution of ribose (e.g., the (N)-methanocarba ring system, various 2'- and 3'-substitutions and 4'-thio substitution of oxygen). Conformational studies of the ribose moiety and its equivalents indicate that the ring oxygen is not required and the North (N) ring conformation is preferred in. binding to the A3AR. Using these observations, a series of ring constrained (N)-methanocarba 5'-uronamide derivatives was recently reported to be highly selective A3AR agonists, the most notable amongst them was MRS3558 113 having a K-i value in binding to the human A(3) receptor of 0.3 nM. C1 NIDDK, Mol Recognit Sect, NIH, LBC, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, NIH, LBC, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 65 TC 14 Z9 14 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2005 VL 5 IS 13 BP 1275 EP 1295 DI 10.2174/156802605774463079 PG 21 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 992YF UT WOS:000233919200007 PM 16305531 ER PT J AU Garfinkel, DJ AF Garfinkel, DJ TI Genome evolution mediated by Ty elements in Saccharomyces SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID REVERSE-TRANSCRIPTASE; TRANSPOSABLE ELEMENTS; GENE ORDER; YEAST; CEREVISIAE; RETROTRANSPOSONS; EXPRESSION; MUTATIONS; MAIZE; DNA AB How mobile genetic elements molded eukaryotic genomes is a key evolutionary question that gained wider popularity when mobile DNA sequences were shown to comprise about half of the human genome. Although Saccharomyces cerevisiae does not suffer such "genome obesity", five families of LTR-retrotransposons, Ty1, Ty2, Ty3, Ty4, and Ty5 elements, comprise about 3% of its genome. The availability of complete genome sequences from several Saccharomyces species, including members of the closely related sensu stricto group, present new opportunities for analyzing molecular mechanisms for chromosome evolution, speciation, and reproductive isolation. In this review I present key experiments from both the pre- and current genomic sequencing eras suggesting how Ty elements mediate genome evolution. Copyright (c) 2005 S. Karger AG, Basel. C1 Natl Canc Inst, Ft Detrick, MD 21702 USA. RP Garfinkel, DJ (reprint author), Natl Canc Inst, POB B, Ft Detrick, MD 21702 USA. EM garfinke@ncifcrf.gov NR 62 TC 35 Z9 37 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2005 VL 110 IS 1-4 BP 63 EP 69 DI 10.1159/000084939 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 953GM UT WOS:000231064600007 PM 16093659 ER PT J AU von Sternberg, R Shapiro, JA AF von Sternberg, R Shapiro, JA TI How repeated retroelements format genome function SO CYTOGENETIC AND GENOME RESEARCH LA English DT Review ID X-CHROMOSOME INACTIVATION; TRANSPOSABLE ELEMENTS; REPETITIVE ELEMENTS; L1 RETROTRANSPOSON; EPIGENETIC INHERITANCE; ARABIDOPSIS-THALIANA; CHROMATIN-STRUCTURE; ANTISENSE PROMOTER; MAMMALIAN GENOME; GYPSY INSULATOR AB Genomes operate as sophisticated information storage systems. Generic repeated signals in the DNA format expression of coding sequence files and organize additional functions essential for genome replication and accurate transmission to progeny cells. Retroelements comprise a major fraction of many genomes and contain a surprising diversity of functional signals. In this article, we summarize some features of the taxonomic distribution of retroelements, especially mammalian SINEs, tabulate functional roles documented for different classes of retroelements, and discuss their potential roles as genome organizers. In particular, the fact that certain retroelements serve as boundaries for heterochromatin domains and provide a significant fraction of scaffolding/matrix attachment regions (S/MARs) suggests that the reversed transcribed component of the genome plays a major architectonic role in higher order physical structuring. Employing an information science model, the "functionalist" perspective on repetitive DNA leads to new ways of thinking about the systemic organization of cellular genomes and provides several novel possibilities involving retroelements in evolutionarily significant genome reorganization. Copyright (c) 2005 S. Karger AG, Basel. C1 Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA. Natl Museum Nat Hist, Smithsonian Inst, Dept Systemat Biol, Washington, DC USA. RP Shapiro, JA (reprint author), Univ Chicago, Dept Biochem & Mol Biol, 920 E,58th St, Chicago, IL 60637 USA. EM jsha@uchicago.edu NR 102 TC 14 Z9 15 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 EI 1424-859X J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2005 VL 110 IS 1-4 BP 108 EP 116 DI 10.1159/000084942 PG 9 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 953GM UT WOS:000231064600010 PM 16093662 ER PT J AU Martin, SL Li, WLP Furano, A Boissinot, S AF Martin, SL Li, WLP Furano, A Boissinot, S TI The structures of mouse and human L1 elements reflect their insertion mechanism SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID INTERSPERSED REPETITIVE DNA; LINE-1 RETROTRANSPOSITION; REVERSE TRANSCRIPTION; ORF1 PROTEIN; RNA-BINDING; SEQUENCE; SUBFAMILY; LINEAGE; GENOME; FAMILY AB L1 is an abundant, interspersed repeated DNA element of mammalian genomes. It has achieved its high copy number via retrotransposition. Like other non-LTR retrotransposons, L1 insertion into chromosomal DNA apparently occurs by target-site primed reverse transcription, or TPRT. L1 retrotransposition often generates elements with 5' truncations that are flanked by a duplication of the genomic target site (TSD). It is typically assumed that the 5' truncated elements are the consequence of poor processivity of the L1 reverse transcriptase. However, we find that the majority of young L1 elements from both the human and mouse genomes are truncated at sequences that can basepair with the target site. Thus, to whatever extent truncation is a consequence of poor processivity, we suggest that truncation is likely to occur when target site sequence can basepair with L I sequence. This finding supports a model for insertion that occurs by two sequential TPRT reactions, the second of which relies upon the homology between the target site and L1. Because perfect heteroduplex formation is not required for all insertions, a dynamic relationship between the primer, template and enzyme during reverse transcription is inferred. 5' truncation may be a successful evolutionary strategy that is exploited by L1 as a means to escape host suppression of transposition. Copyright (c) 2005 S. Karger AG, Basel. C1 Univ Colorado, Sch Med, Dept Cell & Dev Biol, Aurora, CO 80045 USA. Univ Colorado, Sch Med, Human Med Genet Program, Aurora, CO USA. NIDDKD, Sect Genom Struct & Funct, Mol & Cellular Biol Lab, NIH, Bethesda, MD USA. CUNY, Queens Coll, Dept Biol, Flushing, NY USA. RP Martin, SL (reprint author), Univ Colorado, Sch Med, Dept Cell & Dev Biol, POB 6511,12801 E 17th Ave,Mail Stop 8108, Aurora, CO 80045 USA. EM sandy.martin@uchsc.edu FU NIGMS NIH HHS [GM40367] NR 40 TC 39 Z9 39 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2005 VL 110 IS 1-4 BP 223 EP 228 DI 10.1159/000084956 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 953GM UT WOS:000231064600024 PM 16093676 ER PT J AU Marino-Ramirez, L Lewis, KC Landsman, D Jordan, IK AF Marino-Ramirez, L Lewis, KC Landsman, D Jordan, IK TI Transposable elements donate lineage-specific regulatory sequences to host genomes SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID INVERTED-REPEAT ELEMENTS; FACTOR-BINDING SITES; LONG TERMINAL REPEAT; GENE-REGULATION; POLYADENYLATION SIGNAL; LTR-RETROTRANSPOSONS; REGIONS; MOUSE; TRANSCRIPTION; EVOLUTION AB The evolutionary implications of transposable element (TE) influences on gene regulation are explored here. An historical perspective is presented to underscore the importance of TE influences on gene regulation with respect to both the discovery of TEs and the early conceptualization of their potential impact on host genome evolution. Evidence that points to a role for TEs in host gene regulation is reviewed, and comparisons between genome sequences are used to demonstrate the fact that TEs are particularly lineage-specific components of their host genomes. Consistent with these two properties of TEs, regulatory effects and evolutionary specificity, human-mouse genome wide sequence comparisons reveal that the regulatory sequences that are contributed by TEs are exceptionally lineage specific. This suggests a particular mechanism by which TEs may drive the diversification of gene regulation between evolutionary lineages. Copyright (c) 2005 S. Karger AG, Basel. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Univ N Carolina, Sch Informat & Lib Sci, Chapel Hill, NC USA. RP Jordan, IK (reprint author), NIH, Natl Ctr Biotechnol Informat, 8600 Rockville Pike,Bldg 38A,Room N511M, Bethesda, MD 20894 USA. EM jordan@ncbi.nlm.nih.gov RI Landsman, David/C-5923-2009; Marino-Ramirez, Leonardo/I-5759-2013; OI Marino-Ramirez, Leonardo/0000-0002-5716-8512; Landsman, David/0000-0002-9819-6675 FU Intramural NIH HHS [Z99 LM999999] NR 58 TC 62 Z9 66 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 EI 1424-859X J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2005 VL 110 IS 1-4 BP 333 EP 341 DI 10.1159/000084965 PG 9 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 953GM UT WOS:000231064600033 PM 16093685 ER PT J AU Boissinot, S Furano, AV AF Boissinot, S Furano, AV TI The recent evolution of human L1 retrotransposons SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID PRIMATE GENOMIC VARIATION; LINE-1 RETROTRANSPOSITION; ELEMENTS; PROTEIN; SEQUENCES; FAMILY; RECOMBINATION; GENES; SITES AB L1 elements are the most successful retrotransposons in mammals and are responsible for at least 30% of human DNA. Far from being indolent genomic parasites, L1 elements have evolved and amplified rapidly during human evolution. Indeed during just the last 25 million years (MY) five distinct L1 families have emerged and generated tens of thousands of copies. The most recently evolved human specific L1 family is currently active and L1 copies have been accumulating in the human genome at about the same rate per generation as the currently active L1 families in Old World rats and mice. At times during the last 2 5 MY L I activity constituted a significant enough genetic load to be subject to negative selection. During these same times, and in apparent response to the host, L1 underwent adaptive evolution. Understanding the molecular basis for these evolutionary changes should help illuminate one of the least understood but most important aspects of L1 biology, namely the extent and nature of the interaction between L1 and its host. Copyright (c) 2005 S. Karger AG, Basel. C1 CUNY Queens Coll, Dept Biol, Flushing, NY 11367 USA. NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD USA. RP Boissinot, S (reprint author), CUNY Queens Coll, Dept Biol, 65-30 Kissena Blvd, Flushing, NY 11367 USA. EM sboissin@qc1.qc.edu NR 36 TC 14 Z9 15 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2005 VL 110 IS 1-4 BP 402 EP 406 DI 10.1159/000084972 PG 5 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 953GM UT WOS:000231064600040 PM 16093692 ER PT J AU Kelly, FD Levin, HL AF Kelly, FD Levin, HL TI The evolution of transposons in Schizosaccharomyces pombe SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID SACCHAROMYCES RETROTRANSPOSON TY5; VIRUS-LIKE PARTICLES; RNA-POLYMERASE-III; REVERSE TRANSCRIPTION; YEAST RETROTRANSPOSON; SILENT CHROMATIN; GENOME SEQUENCE; FISSION YEAST; COMPREHENSIVE SURVEY; CEREVISIAE GENOME AB Recent studies of the LTR-retrotransposons of Schizosaccharomyces pombe have shed considerable light on their evolution and function. The sequencing of the S. pombe genome allowed analysis of its transposon content. This analysis provides information about the maintenance and loss of transposons in the genome. The results of transposition assays and biochemical analyses demonstrate that the N-terminal protein of Tf1 is functionally equivalent to,the Gag proteins of retroviruses and retrotransposons. Despite this conservation of function, the N-terminal protein of Tf1 lacks any sequence similarity to other known Gag proteins. Sequence analysis and experimental data also indicate that the Tf1 transposons of S. pombe target their integration into specific sites in the host genome. Transposition events resulting from the expression of Tf1 reveal a strong preference for intergenic regions, specifically at pol II promoters in a window 100-400 bp upstream of open reading frames. The complete and partial copies of Tf transposons in the sequenced genome of S. pombe show the same association of integration with promoter regions. This body of work explores how the transposon interacts with the host, the balance between the transposons propagation and loss, and how different families of transposons evolve. Copyright (c) 2005 S. Karger AG, Basel. C1 NICHHD, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Levin, HL (reprint author), NICHHD, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. EM levinh@mail.nih.gov NR 31 TC 6 Z9 6 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2005 VL 110 IS 1-4 BP 566 EP 574 DI 10.1159/000084990 PG 9 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 953GM UT WOS:000231064600058 PM 16093710 ER PT J AU Stanyon, R Bruening, R Stone, G Shearin, A Bigoni, F AF Stanyon, R Bruening, R Stone, G Shearin, A Bigoni, F TI Reciprocal painting between humans, De Brazza's and patas monkeys reveals a major bifurcation in the Cercopithecini phylogenetic tree SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID INSITU SUPPRESSION HYBRIDIZATION; IN-SITU HYBRIDIZATION; AFRICAN-GREEN MONKEY; OLD-WORLD MONKEYS; CHROMOSOMAL SPECIATION; SHOWS; DNA; EVOLUTION; CATARRHINI; HOMOLOGIES AB We report on reciprocal painting between humans and two Cercopithecini species, Erythrocebus patas ( patas monkey) and Cercopithecus neglectus (De Brazza's monkey). Both human and monkeys chromosome-specific probes were made by degenerate oligonucleotide primed PCR (DOP-PCR) from flow sorted chromosomes. Metaphases of both monkey species were first hybridized with human chromosome-specific probes and then human metaphases were hybridized with chromosome paints from each monkey species. The human paint probes detected 34 homologous segments on the C. neglectus karyotype, while the C. neglectus probes, including the Y, revealed 41 homologous segments on the human karyotype. The probes specific for human chromosomes detected 29 homologous segments in the E. patas karyotype, while the patas monkey probes painted 34 segments on the human karyotype. We tested various hypotheses of Cercopithecini phylogeny and taxonomy developed by morphologists, molecular biologists and cytogeneticists. Our hybridization data confirm that fissions (both Robertsonian and non-Robertsonian) are the main mechanism driving the evolutionary trend in Cercopithecini toward higher diploid numbers and strongly suggest an early phylogenetic bifurcation in Cercopithecini. One branch leads to Cercopithecus neglectus/Cercopithecus wolfi while the other line leads to Erythrocebus patas/Chlorocebus aethiops. Allenopithecus nigroviridis may have diverged prior to this major phylogenetic node. Copyright (C) 2005 S. Karger AG, Basel. C1 NCI, BRL, Frederick, MD 21702 USA. RP Stanyon, R (reprint author), NCI, BRL, Bldg 560,Room 11-74A, Frederick, MD 21702 USA. EM stanyonr@mail.ncifcrf.gov OI Stanyon, Roscoe/0000-0002-7229-1092 NR 37 TC 10 Z9 10 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2005 VL 108 IS 1-3 BP 175 EP 182 DI 10.1159/000080813 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 883KX UT WOS:000226011700019 PM 15545727 ER PT J AU Pinto, LA Trivett, MT Wallace, D Higgins, J Baseler, M Terabe, M Belyakov, IM Berzofsky, JA Hildesheim, A AF Pinto, LA Trivett, MT Wallace, D Higgins, J Baseler, M Terabe, M Belyakov, IM Berzofsky, JA Hildesheim, A TI Fixation and cryopreservation of whole blood and isolated mononuclear cells: Influence of different procedures on lymphocyte subset analysis by flow cytometry SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE flow cytometry; whole blood; peripheral blood mononuclear cells; cryopreservation; fixation ID ANTIBODY-BINDING CAPACITY; FRESH; STANDARDIZATION; MULTICENTER; ENUMERATION AB Background: Immunophenotyping of whole blood (WB) and isolated peripheral blood mononuclear cells (PBMCs) is a common tool used to evaluate immune system changes in clinical studies. The development of methods that would allow preservation of samples for flow cytometric analysis is important for the extension of this technology to field testing in settings where the equipment might be not readily accessible. Methods: Three-color flow cytometric analysis was used to determine percentages of T cells and their subsets (CD3(+), CD4(+), CD8(+)), B cells (CD19(+)), and natural killer cells (CD16(+)/56(+)) in WB and PBMCs using variations of a standard stain/fix WB staining procedure (Optilyse) that included staining following fixation and freezing of fixed samples before or after staining. Results: Comparable lymphocyte subset percentages in WB or PBMCs were observed regardless of Optliyse method used (all Ps greater than or equal to 0.8). However, differences in fluorescence intensity for several markers were observed across procedures. Compared with the standard stain/fix procedures, fix/stain decreased the mean fluorescence intensities for CD4, CD8, CD19 and CD16/56 in WB and PBMCs (P less than or equal to 0.03 for these markers P = 0.105 for CD8 in PBMCs). Further decreases in mean fluorescence intensity were seen with the fix/stain/freeze procedure. The stain/fix/freeze yielded intensities largely comparable to those seen with standard stain/fix procedure (P greater than or equal to 0.13), suggesting that, when the markers of interest are known at the time of field collection, implementation of this procedure might be desirable. Fix/freeze/stain resulted in diminution of intensity in general, but they tended to be more modest than those seen for fix/stain/freeze and therefore might be applicable to field studies in instances when the specific markers of interest cannot be defined upfront. Conclusions: Freezing of fixed WB and PBMCs before or after cell surface staining is a reliable method for preserving specimens in field sites for later determination of lymphocyte subset percentages, which are commonly assessed in immunodeficient and cancer patients. Published 2004 Wiley-Liss, Inc. C1 NCI Frederick, SAIC Frederick, HPV Immunol Lab, Frederick, MD 21702 USA. Natl Inst Hlth, Clin Res Ctr, Bethesda, MD USA. Natl Inst Hlth, DCEG, Bethesda, MD USA. RP Pinto, LA (reprint author), NCI Frederick, SAIC Frederick, HPV Immunol Lab, POB B, Frederick, MD 21702 USA. EM lpinto@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 17 TC 13 Z9 15 U1 1 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JAN PY 2005 VL 63B IS 1 BP 47 EP 55 DI 10.1002/cyto.b.20038 PG 9 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 890IB UT WOS:000226503800007 PM 15624203 ER PT J AU Webb, GI Zhang, SM AF Webb, GI Zhang, SM TI K-optimal rule discovery SO DATA MINING AND KNOWLEDGE DISCOVERY LA English DT Article DE exploratory rule discovery; association rules; classification rules; rule search; search space pruning ID SEARCH AB K-optimal rule discovery finds the k rules that optimize a user-specified measure of rule value with respect to a set of sample data and user-specified constraints. This approach avoids many limitations of the frequent itemset approach of association rule discovery. This paper presents a scalable algorithm applicable to a wide range of k-optimal rule discovery tasks and demonstrates its efficiency. C1 Monash Univ, Sch Comp Sci & Software Engn, Melbourne, Vic 3800, Australia. US Natl Lib Med, LHC CgSB, NIH, Bethesda, MD 20894 USA. RP Monash Univ, Sch Comp Sci & Software Engn, POB 75, Melbourne, Vic 3800, Australia. EM webb@infotech.monash.edu.au; szhang@nlm.nih.gov RI Webb, Geoffrey/A-1347-2008; OI Webb, Geoffrey/0000-0001-9963-5169 NR 34 TC 56 Z9 56 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1384-5810 EI 1573-756X J9 DATA MIN KNOWL DISC JI Data Min. Knowl. Discov. PD JAN PY 2005 VL 10 IS 1 BP 39 EP 79 DI 10.1007/s10618-005-0255-4 PG 41 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems SC Computer Science GA 899YV UT WOS:000227182600002 ER PT S AU Shears, SB Yang, L Gabriel, S Ribeiro, CMP AF Shears, SB Yang, L Gabriel, S Ribeiro, CMP BE Schultz, C TI Is intervention in inositol phosphate signaling a useful therapeutic option for cystic fibrosis? SO DEFECTS OF SECRETION IN CYSTIC FIBROSIS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Defects of Secretion CY NOV, 2003 CL Heidelberg, GERMANY ID ACTIVATED CHLORIDE CONDUCTANCE; DEPENDENT PROTEIN-KINASE; AIRWAY EPITHELIA; MYOINOSITOL 3,4,5,6-TETRAKISPHOSPHATE; EXTRACELLULAR NUCLEOTIDES; INTRACELLULAR CALCIUM; NASAL EPITHELIA; CL-CONDUCTANCE; NA+ ABSORPTION; ACINAR-CELLS C1 NIEHS, Inositol Signaling Sect, Lab Signal Transduct, NIH,DHSS, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Pediat & Cyst Fibrosis, Pulm Res & Treatment Ctr, Chapel Hill, NC 27599 USA. RP Shears, SB (reprint author), NIEHS, Inositol Signaling Sect, Lab Signal Transduct, NIH,DHSS, Res Triangle Pk, NC 27709 USA. EM shears@niehs.nih.gov RI Ribeiro, Carla Maria/A-6955-2009 NR 52 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 0-387-23076-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2005 VL 558 BP 103 EP 114 PG 12 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BCV12 UT WOS:000231385600008 ER PT J AU Cromer, KR Bernert, RA Murphy, DL Schmidt, NB AF Cromer, KR Bernert, RA Murphy, DL Schmidt, NB TI Investigation of the dimensional nature of OCD: Factor analysis in a non-clinical sample SO DEPRESSION AND ANXIETY LA English DT Meeting Abstract ID OBSESSIVE-COMPULSIVE DISORDER; SCALE C1 Florida State Univ, Tallahassee, FL 32306 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RI Timpano, Kiara/C-8760-2012 NR 7 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2005 VL 22 IS 4 BP 207 EP 208 PG 2 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 999MU UT WOS:000234394500027 ER PT J AU Rich, BA McClure, EB Vinton, DT Roberson-Nay, R Pine, DS Leibenluft, E AF Rich, BA McClure, EB Vinton, DT Roberson-Nay, R Pine, DS Leibenluft, E TI Preliminary investigation of misinterpretation of facial expressions in childhood anxiety, bipolar disorder, and their comorbidity SO DEPRESSION AND ANXIETY LA English DT Meeting Abstract ID MANIA; DEPRESSION; RECOGNITION; COGNITION; DEFICITS; EMOTION; FACES C1 NIMH, Mood & Anxiety Program, NIH, Bethesda, MD 20892 USA. NR 11 TC 1 Z9 1 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2005 VL 22 IS 4 BP 226 EP 227 PG 2 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 999MU UT WOS:000234394500048 ER PT J AU Horsford, DJ Nguyen, MTT Sellar, GC Kothary, R Arnheiter, H McInnes, RR AF Horsford, DJ Nguyen, MTT Sellar, GC Kothary, R Arnheiter, H McInnes, RR TI Chx10 repression of Mitf is required for the maintenance of mammalian neuroretinal identity SO DEVELOPMENT LA English DT Article DE mouse; Mitf; Chx10; FGF; RPE; neuroretina ID RETINAL-PIGMENT EPITHELIUM; EARLY EYE DEVELOPMENT; HOMEOBOX GENE CHX10; TRANSCRIPTION FACTOR; NEURAL RETINA; OCULAR RETARDATION; MICROPHTHALMIA LOCUS; REGENERATION INVIVO; OPTIC VESICLE; CELLS AB During vertebrate eye development, the cells of the optic vesicle (OV) become either neuroretinal progenitors expressing the transcription factor Chx10, or retinal pigment epithelium (RPE) progenitors expressing the transcription factor Mitf. Chx10 mutations lead to microphthalmia and impaired neuroretinal proliferation. Mitf mutants have a dorsal RPE-to-neuroretinal phenotypic transformation, indicating that Mitf is a determinant of RPE identity. We report here that Mitf is expressed ectopically in the Chx10(orJ/or-J) neuroretina (NR), demonstrating that Chx10 normally represses the neuroretinal expression of Mitf. The ectopic expression of Mitf in the Chx10(or-J/or-J) NR deflects it towards an RFE-like identity; this phenotype results not from a failure of neuroretinal specification, but from a partial loss of neuroretinal maintenance. Using Chx10 and Mitf transgenic and mutant mice, we have identified an antagonistic interaction between Chx10 and Mitf in regulating, retinal cell identity. FGF (fibroblast growth factor) exposure in a developing OV has also been shown to repress Mitf expression. We demonstrate that the repression of Mitf by FGF is Chx10 dependent. indicating that FGF, Chx10 and Mitf are components of a pathway that determines and maintains the identity of the NR. C1 Hosp Sick Children, Res Inst, Program Dev Biol, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Res Inst, Genet Program, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada. NINDS, Lab Dev Neurogenet, NIH, Bethesda, MD 20892 USA. Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. Ottawa Hlth Res Inst, Ottawa, ON K1H 8L6, Canada. Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8M5, Canada. Univ Ottawa, Ctr Neuromuscular Dis, Ottawa, ON K1H 8M5, Canada. Univ Toronto, Dept Pediat, Toronto, ON, Canada. RP McInnes, RR (reprint author), Hosp Sick Children, Res Inst, Program Dev Biol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM mcinnes@sickkids.ca OI Kothary, Rashmi/0000-0002-9239-7310 NR 53 TC 108 Z9 110 U1 1 U2 8 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JAN PY 2005 VL 132 IS 1 BP 177 EP 187 DI 10.1242/dev.01571 PG 11 WC Developmental Biology SC Developmental Biology GA 891XN UT WOS:000226614400017 PM 15576400 ER PT S AU Thompson, KG Bichot, NP AF Thompson, KG Bichot, NP BE VanPelt, J Kamermans, M Levelt, CN VanOoyen, A Ramakers, GJA Roelfsema, PR TI A visual salience map in the primate frontal eye field SO DEVELOPMENT, DYNAMICS AND PATHOLOGY OF NEURONAL NETWORKS: FROM MOLECULES TO FUNCTIONAL CIRCUITS SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 23rd International Summer School of Brain Research CY AUG 25-29, 2003 CL Royal Netherlands Acad Arts & Sci, Amstedram, NETHERLANDS SP Royal Netherlands Acad Arts & Sci, Netherlands Inst Brain Res, Roual Netherlands Acad Arts & Sci, Netherlands Ophthalm Res Inst HO Royal Netherlands Acad Arts & Sci ID SACCADE TARGET SELECTION; PARIETAL CORTEX; SUPERIOR COLLICULUS; ATTENTION; MACAQUE; SEARCH; NEURONS; REPRESENTATION; MODEL; INACTIVATION AB Models of attention and saccade target selection propose that within the brain there is a topographic map of visual salience that combines bottom-up and top-down influences to identify locations for further processing. The results of a series of experiments with monkeys performing visual search tasks have identified a population of frontal eye field (FEF) visually responsive neurons that exhibit all of the characteristics of a visual salience map. The activity of these FEF neurons is not sensitive to specific features of visual stimuli; but instead, their activity evolves over time to select the target of the search array. This selective activation reflects both the bottom-up intrinsic conspicuousness of the stimuli and the top-down knowledge and goals of the viewer. The peak response within FEF specifies the target for the overt gaze shift. However, the selective activity in FEF is not in itself a motor command because the magnitude of activation reflects the relative behavioral significance of the different stimuli in the visual scene and occurs even when no saccade is made. Identifying a visual salience map in FEF validates the theoretical concept of a salience map in many models of attention. In addition, it strengthens the emerging view that FEF is not only involved in producing overt gaze shifts, but is also important for directing covert spatial attention. C1 LSR, NEI, NIH, Bethesda, MD 20892 USA. NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Thompson, KG (reprint author), LSR, NEI, NIH, Bldg 49,Rm 2A50,MSC 4435, Bethesda, MD 20892 USA. EM kgt@lsr.nei.nih.gov NR 50 TC 181 Z9 182 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-51663-8 J9 PROG BRAIN RES PY 2005 VL 147 BP 251 EP 262 DI 10.1016/S0079-6123(04)47019-8 PG 12 WC Neurosciences SC Neurosciences & Neurology GA BBH28 UT WOS:000225509400019 PM 15581711 ER PT J AU Kozlowski, DJ Whitfield, TT Hukriede, NA Lam, WK Weinberg, ES AF Kozlowski, DJ Whitfield, TT Hukriede, NA Lam, WK Weinberg, ES TI The zebrafish dog-eared mutation disrupts eya1, a gene required for cell survival and differentiation in the inner ear and lateral line SO DEVELOPMENTAL BIOLOGY LA English DT Article DE eya1; otic vesicle; cristae; fate mapping; zebrafish; bmp4 ID EYES-ABSENT GENE; BRANCHIOOTORENAL SYNDROME; HUMAN HOMOLOG; DANIO-RERIO; EXPRESSION; EMBRYO; HINDBRAIN; DEAFNESS; MICE; PHOSPHATASE AB To understand the molecular basis of sensory organ development and disease, we have cloned and characterized the zebrafish mutation dog-eared (dog) that is defective in formation of the inner ear and lateral line sensory systems. The dog locus encodes the eyes absent-1 (eya1) gene and single point mutations were found in three independent dog alleles, each prematurely truncating the expressed protein within the Eya domain. Moreover, morpholino-mediated knockdown of eya1 gene function phenocopies the dog-eared mutation. In zebrafish, the eya1 gene is widely expressed in placode-derived sensory organs during embryogenesis but Eya 1 function appears to be primarily required for survival of sensory hair cells in the developing ear and lateral line neuromasts. Increased levels of apoptosis occur in the migrating primordia of the posterior lateral line in dog embryos and as well as in regions of the developing otocyst that are mainly fated to give rise to sensory cells of the cristae. Importantly, mutation of the EYA1 or EYA4 gene causes hereditary syndromic deafness in humans. Determination of eya1 gene function during zebrafish organogenesis will facilitate understanding the molecular etiology of human vestibular and hearing disorders. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. Med Coll Georgia, Inst Mol Med & Genet Cellular Biol & Anat, Augusta, GA 30912 USA. Univ Sheffield, Sch Med & Biomed Sci, Dept Biomed Sci, Ctr Dev Genet, Sheffield S10 2TN, S Yorkshire, England. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Weinberg, ES (reprint author), Univ Penn, Dept Biol, 415 S Univ Ave, Philadelphia, PA 19104 USA. EM eweinber@sas.upenn.edu RI Whitfield, Tanya/E-6203-2010; OI Whitfield, Tanya/0000-0003-1575-1504 FU NIDCD NIH HHS [F32-DC0311, R01-DC03080] NR 57 TC 77 Z9 79 U1 1 U2 6 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 2005 VL 277 IS 1 BP 27 EP 41 DI 10.1016/j.ydbio.2004.08.033 PG 15 WC Developmental Biology SC Developmental Biology GA 879TG UT WOS:000225741200003 PM 15572137 ER PT J AU Kenworthy, LE Black, DO Wallace, GL Ahluvalia, T Wagner, AE Sirian, LM AF Kenworthy, LE Black, DO Wallace, GL Ahluvalia, T Wagner, AE Sirian, LM TI Disorganization: The forgotten executive dysfunction in high-functioning autism (HFA) spectrum disorders SO DEVELOPMENTAL NEUROPSYCHOLOGY LA English DT Article ID ASPERGERS-DISORDER; JOINT ATTENTION; YOUNG-CHILDREN; BRAIN; MIND; INDIVIDUALS; MEMORY; PERFORMANCE; DEFICIT; INTACT AB Executive function (EF) abilities were investigated in 72 children with high-functioning autism (HFA) spectrum disorders through the collection of parent ratings and performance on laboratory measures of EF. In addition, discrepancy analysis was used to isolate executive functioning on tasks that carry multiple demands. Comparison of HFA and Asperger Disorder (AD) groups did not reveal consistent differences in EF. Results did indicate global EF deficits in the combined group of children with HFA and AD. Within the EF domain, specific deficits in flexibility and organization were most prominent. C1 Ctr Autism Spectrum Disorders, Childrens Natl Med Ctr, Rockville, MD 20850 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Div Pediat Translat Res & Treatment Dev, Bethesda, MD 20892 USA. American Univ, Dept Psychol, Washington, DC 20016 USA. RP Kenworthy, LE (reprint author), Ctr Autism Spectrum Disorders, Childrens Natl Med Ctr, 14801 Phys Lane,Ste 173, Rockville, MD 20850 USA. EM lkenwort@cnmc.org RI Wallace, Gregory/A-4789-2008 NR 53 TC 45 Z9 46 U1 3 U2 16 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 2005 VL 28 IS 3 BP 809 EP 827 DI 10.1207/s15326942dn2803_4 PG 19 WC Psychology, Developmental; Psychology; Psychology, Experimental SC Psychology GA 987UC UT WOS:000233541800004 PM 16266250 ER PT J AU Waage-Baudet, H Dunty, WC Dehart, DB Hiller, S Sulik, KK AF Waage-Baudet, H Dunty, WC Dehart, DB Hiller, S Sulik, KK TI Immunohistochemical and microarray analyses of a mouse model for the Smith-Lemli-Opitz syndrome SO DEVELOPMENTAL NEUROSCIENCE LA English DT Review DE Smith-Lemli-Opitz syndrome; autism; sonic hedgehog; netrin; microarray; cholesterol biosynthesis ID CILIARY NEUROTROPHIC FACTOR; DEFECTIVE CHOLESTEROL-BIOSYNTHESIS; MICROTUBULE-ASSOCIATED PROTEINS; MULTIPLE CONGENITAL-ANOMALIES; COLORECTAL-CANCER DCC; II-DEFICIENT MICE; ALZHEIMERS-DISEASE; AXON GUIDANCE; SONIC-HEDGEHOG; OLIGONUCLEOTIDE ARRAYS AB The Smith-Lemli-Opitz syndrome is a mental retardation/malformation syndrome with behavioral components of autism. It is caused by a deficiency in 3 beta-hydroxysteroid-Delta(7)-reductase (DHCR7), the enzyme required for the terminal enzymatic step of cholesterol biosynthesis. The availability of Smith-Lemli-Opitz syndrome mouse models has made it possible to investigate the genesis of the malformations associated with this syndrome. Dhcr7 gene modification (Dhcr7-/-) results in neonatal lethality and multiple organ system malformations. Pathology includes cleft palate, pulmonary hypoplasia, cyanosis, impaired cortical response to glutamate, and hypermorphic development of hindbrain serotonergic neurons. For the current study, hindbrain regions microdissected from gestational day 14 Dhcr7-/-, Dhcr7+/- and Dhcr7+/+ fetuses were processed for expression profiling analyses using Affymetrix oligonucleotide arrays and filtered using statistical significance (S-score) of change in gene expression. Of the 12,000 genes analyzed, 91 were upregulated and 98 were downregulated in the Dhcr7-/- hindbrains when compared to wild-type animals. Fewer affected genes, representing a reduced affect on these pathways, were identified in heterozygous animals. Hierarchical clustering identified altered expression of genes associated with cholesterol homeostasis, cell cycle control and apoptosis, neurodifferentiation and embryogenesis, transcription and translation, cellular transport, neurodegeneration, and neuronal cytoskeleton. Of particular interest, Dhcr7 gene modification elicited dynamic changes in genes involved in axonal guidance. In support of the microarray findings, immunohistochemical analyses of the netrin/deleted in colorectal cancer axon guidance pathway illustrated midline commissural deficiencies and hippocampal pathfinding errors in Dhcr7-/- mice. The results of these studies aid in providing insight into the genesis of human cholesterol-related birth defects and neurodevelopmental disorders and highlight specific areas for future investigation. Copyright (c) 2005 S. Karger AG, Basel. C1 Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA. Univ N Carolina, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA. NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA. RP Sulik, KK (reprint author), Univ N Carolina, Sch Med, Ctr Alcohol Studies, 3019A Thurston Bowles Bldg,CB 7178, Chapel Hill, NC 27599 USA. EM mouse@med.unc.edu NR 116 TC 16 Z9 17 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2005 VL 27 IS 6 BP 378 EP 396 DI 10.1159/000088453 PG 19 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 982ZT UT WOS:000233201600003 PM 16280635 ER PT J AU Allhusen, V Belsky, J Kersey, HB Booth-Laforce, C Bradley, R Brownell, CA Burchinal, M Campbell, SB Clarke-Stewart, KA Cox, M Friedman, SL Hirsh-Pasek, K Houts, R Huston, A Kelly, JF Lanza, S Marshall, N Mason, T McCartney, K McLeod, L Morrison, FJ O'Brien, M Owen, MT Payne, CC Pianta, R Robeson, WW Serpell, Z Spieker, S Teufel, J Vandell, DL Weintraub, M AF Allhusen, V Belsky, J Kersey, HB Booth-Laforce, C Bradley, R Brownell, CA Burchinal, M Campbell, SB Clarke-Stewart, KA Cox, M Friedman, SL Hirsh-Pasek, K Houts, R Huston, A Kelly, JF Lanza, S Marshall, N Mason, T McCartney, K McLeod, L Morrison, FJ O'Brien, M Owen, MT Payne, CC Pianta, R Robeson, WW Serpell, Z Spieker, S Teufel, J Vandell, DL Weintraub, M CA NICHD Early Child Care Res Network TI Predicting individual differences in attention, memory, and planning in first graders from experiences at home, child care, and school SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID EXECUTIVE FUNCTION; LANGUAGE-DEVELOPMENT; PRESCHOOL-CHILDREN; FAMILY PREDICTORS; BEHAVIOR; ENTRY; PERFORMANCE; ENVIRONMENT; READINESS; DEFICITS AB This study adds to the growing literature linking children's experiences in the environment to individual differences in their developing skills in attention, memory. and planning. The authors asked about the extent to which stimulating and sensitive care in the family and in the child-care or school environments would predict these cognitive outcomes. The authors also questioned the primacy of experiences in the first 3 years of life. Data from a sample of 700 first graders whose experiences in the home and in child care or school were evaluated since early infancy revealed that the cumulative quality of the child-rearing environment was related to attention and memory but not to planning and that the quality of the family environment was more strongly associated with outcomes than was the quality of child care and of school. The quality of both children's early (6 through 36 months) and later (54 months and first grade) environments predicted performance on the attention and memory tasks. C1 NICHD, Early Child Care Res Network, Rockville, MD 20852 USA. RP Allhusen, V (reprint author), NICHD, Early Child Care Res Network, 6100 Executive Blvd,Room 2C01, Rockville, MD 20852 USA. RI Marshall, Nancy/C-3428-2012 NR 86 TC 84 Z9 84 U1 8 U2 24 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 EI 1939-0599 J9 DEV PSYCHOL JI Dev. Psychol. PD JAN PY 2005 VL 41 IS 1 BP 99 EP 114 DI 10.1037/0012-1649.41.1.99 PG 16 WC Psychology, Developmental SC Psychology GA 887IE UT WOS:000226298400009 ER PT J AU Kino, T De Martino, MU Charmandari, E Ichijo, T Outas, T Chrousos, GP AF Kino, T De Martino, MU Charmandari, E Ichijo, T Outas, T Chrousos, GP TI HIV-1 accessory protein Vpr inhibits the effect of insulin on the Foxo subfamily of forkhead transcription factors by interfering with their binding to 14-3-3 proteins - Potential clinical implications regarding the insulin resistance of HIV-1-infected patients SO DIABETES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CELL-CYCLE; GENE-EXPRESSION; GLUCOCORTICOID-RECEPTOR; FACTOR FKHR; DIFFERENTIAL REGULATION; ANTIRETROVIRAL THERAPY; MYOCARDIAL-INFARCTION; T-CELLS; INFECTION AB HIV-1 accessory protein Vpr arrests host cells at the G2/M phase of the cell cycle by interacting with members of the protein family 14-3-3, which regulate the activities of "partner" molecules by binding to their phosphorylated serine or threonine residues and changing their intracellular localization and/or stability. Vpr does this by facilitating the association of 14-3-3 to its partner protein Cdc25C, independent of the latter's phosphorylation status. Here we report that the same viral protein interfered with and altered the activity of another 14-3-3 partner molecule, Foxo3a, a subtype of the forkhead transcription factors, by inhibiting its association with 14-3-3. Foxo3a's transcriptional activity is normally suppressed by insulin-induced translocation of this protein from the nucleus into the cytoplasm. Vpr inhibited the ability of insulin or its downstream protein kinase Akt to change the intracellular localization of Foxo3a preferentially to the cytoplasm. This HIV-1 protein also interfered with insulin-induced co-precipitation of 14-3-3 and Foxo3a in vivo and antagonized the negative effect of insulin on Foxo3a-induced transactivation of a FOXO-responsive promoter. Moreover, Vpr antagonized insulin-induced suppression of the mRNA expression of the glucose 6-phosphatase, manganese superoxide dismutase, and sterol carrier protein 2 genes, which are known targets of insulin and FOXO, in HepG2 cells. These findings indicate that Vpr interferes with the suppressive effects of insulin on FOXO-mediated transcription of target genes via 14-3-3. Vpr thus may contribute to the tissue-selective insulin resistance often observed in HIV-1-infected individuals. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Clin Res Ctr, Bethesda, MD 20892 USA. NCI, Womens Canc Sect, Pathol Branch, Bethesda, MD 20892 USA. RP Kino, T (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Clin Res Ctr, 10 Ctr Dr,MSC 1109,Bldg 10,Room 1-3140, Bethesda, MD 20892 USA. EM kinot@mail.nih.gov RI Charmandari, Evangelia/B-6701-2011 NR 56 TC 33 Z9 34 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2005 VL 54 IS 1 BP 23 EP 31 DI 10.2337/diabetes.54.1.23 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 886SA UT WOS:000226247500004 PM 15616007 ER PT J AU Obrosova, IG Pacher, P Szabo, C Zsengeller, Z Hirooka, H Stevens, MJ Yorek, MA AF Obrosova, IG Pacher, P Szabo, C Zsengeller, Z Hirooka, H Stevens, MJ Yorek, MA TI Aldose reductase inhibition counteracts oxidative-nitrosative stress and poly(ADP-ribose) polymerase activation in tissue sites for diabetes complications SO DIABETES LA English DT Article ID PROTEIN-KINASE-C; NERVE-CONDUCTION-VELOCITY; ENDOTHELIAL GROWTH-FACTOR; CULTURED RETINAL PERICYTES; PIGMENT EPITHELIAL-CELLS; POLYOL PATHWAY; PERIPHERAL-NERVE; FACTOR OVEREXPRESSION; VASCULAR REACTIVITY; LIPOIC ACID AB This study evaluated the effects of aldose reductase inhibition on diabetes-induced oxidative-nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation. In animal experiments, control and streptozotocin-induced diabetic rats were treated with or without the aldose reductase inhibitor (ARI) fidarestat (16 mg kg(-1) - day(-1)) for 6 weeks starting from induction of diabetes. Sorbitol pathway intermediate, but not glucose, accumulation in sciatic nerve and retina was completely prevented in diabetic rats treated with fidarestat. Sciatic motor nerve conduction velocity, hindlimb digital sensory nerve conduction velocity, and sciatic nerve concentrations of two major nonenzymatic antioxidants, glutathione and ascorbate, were reduced in diabetic versus control rats, and these changes were prevented in diabetic rats treated with fidarestat. Fidarestat prevented the diabetes-induced increase in nitrotyrosine (a marker of peroxynitrite-induced injury) and poly(ADP-ribose) immunoreactivities in sciatic nerve and retina. Fidarestat counteracted increased superoxide formation in aorta and epineurial vessels and in in vitro studies using hyperglycemia-exposed endothelial cells, and the DCF test/flow cytometry confirmed the endothelial origin of this phenomenon. Fidarestat did not cause direct inhibition of PARP activity in a cell-free system containing PARP and NAD+ but did counteract high-glucose-induced PARP activation in Schwann cells. In conclusion, aldose reductase inhibition counteracts diabetes-induced nitrosative stress and PARP activation in sciatic nerve and retina. These findings reveal the new beneficial properties of fidarestat, thus further justifying the ongoing clinical trials of this specific, potent, and low-toxic ARI. C1 Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. NIH, Lab Physiol Studies, NIAAA, Bethesda, MD 20892 USA. Inotek Pharmaceut, Beverly, MA USA. Drug Dev Res Labs, Kenkyusho, Mie, Japan. Univ Iowa, Vet Affairs Med Ctr, Iowa City, IA 52242 USA. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. RP Obrosova, IG (reprint author), Louisiana State Univ, Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. EM obrosoig@pbrc.edu RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU Intramural NIH HHS [Z99 AA999999]; NHLBI NIH HHS [HL/DK71215-01]; NIDDK NIH HHS [DK058005-04, DK59809-01, K01 DK059809, R01 DK058005] NR 65 TC 110 Z9 116 U1 0 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2005 VL 54 IS 1 BP 234 EP 242 DI 10.2337/diabetes.54.1.234 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 886SA UT WOS:000226247500031 PM 15616034 ER PT J AU Duttaroy, A Kanakaraj, P Osborn, BL Schneider, H Pickeral, OK Chen, C Zhang, GY Kaithamana, S Singh, M Schulingkamp, R Crossan, D Bock, J Kaufman, TE Reavey, P Carey-Barber, M Krishnan, SR Garcia, A Murphy, K Siskind, JK McLean, MA Cheng, S Ruben, S Birse, CE Blondel, O AF Duttaroy, A Kanakaraj, P Osborn, BL Schneider, H Pickeral, OK Chen, C Zhang, GY Kaithamana, S Singh, M Schulingkamp, R Crossan, D Bock, J Kaufman, TE Reavey, P Carey-Barber, M Krishnan, SR Garcia, A Murphy, K Siskind, JK McLean, MA Cheng, S Ruben, S Birse, CE Blondel, O TI Development of a long-acting insulin analog using albumin fusion technology SO DIABETES LA English DT Article ID RECEPTOR-BINDING; HIGH-AFFINITY; C-PEPTIDE; GLARGINE; EXPRESSION; PROTEIN; PHARMACOKINETICS; PHARMACODYNAMICS; INFUSION; THERAPY AB The primary therapeutic goal for the treatment of diabetes is maintenance of along-term, near-normoglycemic condition and prevention of the onset or progression of the complications associated with the disease. Although several analogs of human insulin have been developed, the currently prescribed long-acting insulin analogs do not provide a stable basal glycemia for more than a few hours. Here, we report the development of Albulin, a long-acting insulin analog obtained by direct gene fusion of a singlechain human insulin to human serum albumin. Albulin showed an elimination t(1/2) of similar to7 h in normoglycemic mice. In vitro pharmacodynamic profiles for Albulin characterized by receptor binding, inhibition of gluconeogenesis, induction of glucose uptake, and global regulation of gene expression in relevant cell types showed that Albulin produced similar activity profiles compared with that of recombinant human insulin. A single Albulin administration in vivo normalized blood glucose level in diabetic mice in a relatively peakless and sustained (24-h) fashion. A further reduction in glucose levels was achieved by administering a recombinant human insulin a few hours after Albulin injection in mice, indicating the potential for Albulin therapy in combination with available fast-acting insulin derivatives. In summary, Albulin displays characteristics of a potent long-acting insulin analog that can be evaluated for use as a novel insulin therapy for patients with insulin-dependent diabetes. C1 NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. RP Blondel, O (reprint author), NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, 6707 Democracy Blvd,Rm 606,MSC5460, Bethesda, MD 20892 USA. EM olivier.blondel@verizon.net NR 33 TC 71 Z9 80 U1 1 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2005 VL 54 IS 1 BP 251 EP 258 DI 10.2337/diabetes.54.1.251 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 886SA UT WOS:000226247500033 PM 15616036 ER PT J AU de Courten, BV Hanson, RL Funahashi, T Lindsay, RS Matsuzawa, Y Tanaka, S Thameem, F Gruber, JD Froguel, P Wolford, JK AF de Courten, BV Hanson, RL Funahashi, T Lindsay, RS Matsuzawa, Y Tanaka, S Thameem, F Gruber, JD Froguel, P Wolford, JK TI Common polymorphisms in the adiponectin gene ACDC are not associated with diabetes in Pima Indians SO DIABETES LA English DT Article ID AUTOSOMAL GENOMIC SCAN; INSULIN SENSITIVITY; MATHEMATICAL APPROACH; SUSCEPTIBILITY GENES; METABOLIC SYNDROME; GLUCOSE-TOLERANCE; OBESITY; PROTEIN; LOCI; POPULATION AB Adiponectin is an abundant adipose tissue-derived protein with important metabolic effects. Plasma adiponectin levels are decreased in obese individuals, and low adiponectin levels predict insulin resistance and type 2 diabetes. Two variants in the adiponectin gene ACDC have been previously associated with plasma adiponectin levels, obesity, insulin resistance, and type 2 diabetes. To determine the role of genetic variation in ACDC in susceptibility to obesity and type 2 diabetes in Pima Indians, we screened the promoter, exons, and exonintron boundaries of the gene to identify allelic variants. We identified 17 informative polymorphisms that comprised four common (minor allele frequency > 15%) linkage disequilibrium clusters consisting of 1-4 variants each. We genotyped one representative polymorphism from each cluster in 1,338 individuals and assessed genotypic association with type 2 diabetes, BMI, serum lipid levels, serum adiponectin levels, and measures of insulin sensitivity and secretion. None of the ACDC variants were associated with type 2 diabetes, BMI, or measures of insulin sensitivity or secretion. One variant, single nucleotide polymorphism (SNP)12823, was associated with serum adiponectin levels (P = 0.002), but this association explained only 2% of the variance of serum adiponectin levels. Our findings suggest that these common ACDC polymorphisms do not play a major role in susceptibility to obesity or type 2 diabetes in this population. C1 Translat Genomics Res Inst, Diabet Res Unit, Phoenix, AZ USA. NIDDK, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ USA. Osaka Univ, Grad Sch Med, Dept Internal Med & Mol Sci, Osaka, Japan. Inst Pasteur, Inst Biol, CNRS, F-59019 Lille, France. RP Wolford, JK (reprint author), Translat Genomics Res Inst, Diabet Res Unit, 400 N 5th St, Phoenix, AZ USA. EM jwolford@tgen.org RI Hanson, Robert/O-3238-2015; OI Hanson, Robert/0000-0002-4252-7068; de Courten, Barbora/0000-0001-8760-2511 NR 25 TC 53 Z9 55 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2005 VL 54 IS 1 BP 284 EP 289 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 886SA UT WOS:000226247500037 ER PT J AU Saremi, A Nelson, RG Tulloch-Reid, M Hanson, RL Sievers, ML Taylor, GW Shlossman, M Bennett, PH Genco, R Knowler, WC AF Saremi, A Nelson, RG Tulloch-Reid, M Hanson, RL Sievers, ML Taylor, GW Shlossman, M Bennett, PH Genco, R Knowler, WC TI Periodontal disease and mortality in type 2 diabetes SO DIABETES CARE LA English DT Article ID CORONARY-HEART-DISEASE; PIMA-INDIANS; CARDIOVASCULAR-DISEASE; GLYCEMIC CONTROL; MELLITUS; RISK; POPULATION; PREVALENCE; WEIGHT; INDEX AB OBJECTIVE - Periodontal disease may contribute to the increased mortality associated with diabetes. RESEARCH DESIGN AND METHODS - In a prospective longitudinal study of 628 subjects aged greater than or equal to35 years, we examined the effect of periodontal disease on overall and cardiovascular disease mortality in Pima Indians with type 2 diabetes. Periodontal abnormality was classified as no or mild, moderate, and severe, based on panoramic radiographs and clinical dental examinations. RESULTS - During a median follow-up of 11 years (range 0.3-16), 204 subjects died. The age- and sex-adjusted death rates for all natural causes expressed as the number of deaths per 1,000 person-years of follow-up were 3.7 (95% Cl 0.7-6.6) for no or mild periodontal disease, 19.6 (10.7-28.5) for moderate periodontal disease, and 28.4 (22.3-34.6) for severe periodontal disease. Periodontal disease predicted deaths from ischemic heart disease (IHD) (P trend = 0.04) and diabetic nephropathy (P trend < 0.01). Death rates from other causes were riot associated with periodontal disease. After adjustment for age, sex, duration of diabetes, HbA(lc), macroalbuminuria, BMI, serum cholesterol concentration, hypertension, electrocardiographic abnormalities, and current smoking in a proportional hazards model, subjects with severe periodontal disease had 3.2 tunes the risk (95% Cl 1.1-9.3) of cardiorenal mortality (IHD and diabetic nephropathy combined) compared with the reference group (no or mild periodontal disease and moderate periodontal disease combined). CONCLUSIONS - Periodontal disease is a strong predictor of mortality from IHD and diabetic nephropathy in Pima Indians with type 2 diabetes. The effect of periodontal disease is in addition to the effects of traditional risk factors lot these diseases. Diabetes Care 28:27-32, 2005. C1 NIDDKD, Phoenix, AZ USA. Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. SUNY Buffalo, Buffalo, NY USA. RP Nelson, RG (reprint author), 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM rgnelson@mail.nih.gov RI Nelson, Robert/B-1470-2012; Tulloch-Reid, Marshall/E-4383-2012; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU NIDCR NIH HHS [DE-06514] NR 35 TC 165 Z9 175 U1 2 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2005 VL 28 IS 1 BP 27 EP 32 DI 10.2337/diacare.28.1.27 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 886SC UT WOS:000226247700006 PM 15616229 ER PT J AU Armoni, M Harel, C Krits, N Chen, H Quon, MJ Karnieli, E AF Armoni, M Harel, C Krits, N Chen, H Quon, MJ Karnieli, E TI FOXO1 as a master regulator of PPAR gamma and GLUT4 gene promoters in adipocytes: a novel paradigm to increase insulin sensitivity SO DIABETOLOGIA LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 10-15, 2005 CL Athens, GREECE SP European Assoc Study Diabet C1 Technion Israel Inst Technol, Inst Endocrinol Diabet & Metab, Rambam Med Ctr, Haifa, Israel. Technion Israel Inst Technol, Fac Med, Haifa, Israel. NIH, NCCAM, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PY 2005 VL 48 SU 1 MA 564 BP A208 EP A208 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962OX UT WOS:000231743201163 ER PT J AU Berger, K Hun, CY Manganiello, VC Stenson-Holst, L Degerman, E AF Berger, K Hun, CY Manganiello, VC Stenson-Holst, L Degerman, E TI The role of adipose tissue and adipose tissue-derived factors in the development of type 2 diabetes. Studies in a new type 2 diabetes animal model lacking phosphodiesterase 3B SO DIABETOLOGIA LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 10-15, 2005 CL Athens, GREECE SP European Assoc Study Diabet C1 Lund Univ, Lund, Sweden. NIH, Pulm Crit Care Med Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PY 2005 VL 48 SU 1 MA 555 BP A205 EP A205 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962OX UT WOS:000231743201154 ER PT J AU Cali, AMG Ma, L Hanson, RL Que, LN Kobes, S Bogardus, C Sabra, M Shuldiner, AR Baier, LJ AF Cali, AMG Ma, L Hanson, RL Que, LN Kobes, S Bogardus, C Sabra, M Shuldiner, AR Baier, LJ TI A non-synonymous substitution (R1467H) in ARHGEF11 is associated with insulin resistance and type 2 diabetes in Pima Indians SO DIABETOLOGIA LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 10-15, 2005 CL Athens, GREECE SP European Assoc Study Diabet C1 Univ Verona, Dept Biomed & Surg Sci, Sect Endocrinol & Metab Dis, I-37100 Verona, Italy. NIDDK, NIH, Phoenix, AZ USA. Univ Maryland, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PY 2005 VL 48 SU 1 MA 373 BP A140 EP A140 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962OX UT WOS:000231743200374 ER PT J AU Egan, JM Zhou, J Carlson, OD Kim, BJ Wustner, J Sadeghi, H AF Egan, JM Zhou, J Carlson, OD Kim, BJ Wustner, J Sadeghi, H TI Glucagon-like peptide-1, fused to human transferrin, is a long-acting and potent anti-hyperglycemic agent SO DIABETOLOGIA LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 10-15, 2005 CL Athens, GREECE SP European Assoc Study Diabet C1 NIA, Diabet Sect 23, NIH, Baltimore, MD 21224 USA. Biorexis Pharmaceut Corp, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PY 2005 VL 48 SU 1 MA 548 BP A202 EP A202 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962OX UT WOS:000231743201147 ER PT J AU Kataja-Tuomola, M Sundell, J Mannisto, S Virtanen, MJ Albanes, D Virtamo, J AF Kataja-Tuomola, M Sundell, J Mannisto, S Virtanen, MJ Albanes, D Virtamo, J TI Effect of alpha-tocopherol and beta-carotene supplementation on the incidence of type 2 diabetes in Finnish male smokers SO DIABETOLOGIA LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 10-15, 2005 CL Athens, GREECE SP European Assoc Study Diabet C1 Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PY 2005 VL 48 SU 1 MA 362 BP A137 EP A137 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962OX UT WOS:000231743200363 ER PT J AU Martinez-Calatrava, MJ Gonzalez-Sanchez, JL Franks, PW Martinez-Larrad, MT Barroso, I Wareham, NJ Zabena, CA Serrano-Rios, M AF Martinez-Calatrava, MJ Gonzalez-Sanchez, JL Franks, PW Martinez-Larrad, MT Barroso, I Wareham, NJ Zabena, CA Serrano-Rios, M TI A haplotype combination in endothelial nitric oxide synthase gene is associated with metabolic syndrome and related parameters SO DIABETOLOGIA LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 10-15, 2005 CL Athens, GREECE SP European Assoc Study Diabet C1 Hosp Clin San Carlos, Madrid, Spain. NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. Wellcome Trust Sanger Inst, Metab Dis Grp, Cambridge, England. MRC, Epidemiol Unit, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PY 2005 VL 48 SU 1 MA 323 BP A122 EP A122 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962OX UT WOS:000231743200324 ER PT J AU Nilsson, R Andersson, U Sward, K Ahmad, F Manganiello, V Degerman, E AF Nilsson, R Andersson, U Sward, K Ahmad, F Manganiello, V Degerman, E TI Functional role of caveolae in insulin-induced activation of phosphodiesterase 3B in primary adipocytes SO DIABETOLOGIA LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 10-15, 2005 CL Athens, GREECE SP European Assoc Study Diabet C1 Div Diabet Metab & Endocrinol, Lund, Sweden. NHLBI, Pulm & Crit Care Med Branch, Bethesda, MD USA. RI sward, karl/J-5798-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PY 2005 VL 48 SU 1 MA 655 BP A240 EP A240 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962OX UT WOS:000231743201253 ER PT J AU Nishikawa, T Ito, Y Saito, J Soyama, A Ito, H Kino, T Chrousos, G AF Nishikawa, T Ito, Y Saito, J Soyama, A Ito, H Kino, T Chrousos, G TI Possible involvement of local aldosterone production by renal mesangial cells in diabetic nephropathy SO DIABETOLOGIA LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 10-15, 2005 CL Athens, GREECE SP European Assoc Study Diabet C1 Yokohama Rosai Hosp, Yokohama, Kanagawa, Japan. NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PY 2005 VL 48 SU 1 MA 9 BP A6 EP A6 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962OX UT WOS:000231743200010 ER PT J AU Zeggini, E Rayner, W Groves, CJ Hanson, RL Mitchell, BD O'Connell, J Vaxillaire, M Froguel, P Hunt, S Cardon, L Elbein, SC Shuldiner, A Deloukas, P McCarthy, MI AF Zeggini, E Rayner, W Groves, CJ Hanson, RL Mitchell, BD O'Connell, J Vaxillaire, M Froguel, P Hunt, S Cardon, L Elbein, SC Shuldiner, A Deloukas, P McCarthy, MI TI Linkage disequilibrium mapping of the type 2 diabetes susceptibility variants on chromosome Iq in European populations SO DIABETOLOGIA LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Association-for-the-Study-of-Diabetes CY SEP 10-15, 2005 CL Athens, GREECE SP European Assoc Study Diabet C1 Univ Oxford, Oxford OX1 2JD, England. NIDDK, NIH, Phoenix, AZ USA. Univ Maryland, College Pk, MD 20742 USA. Inst Pasteur, F-59019 Lille, France. Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England. Wellcome Trust Sanger Inst, Hinxton, England. Univ Arkansas, Fayetteville, AR 72701 USA. RI Deloukas, Panos/B-2922-2013 OI Deloukas, Panos/0000-0001-9251-070X NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PY 2005 VL 48 SU 1 MA 340 BP A128 EP A128 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 962OX UT WOS:000231743200341 ER PT J AU Bloss, G AF Bloss, G TI Measuring the health consequences of alcohol consumption: Current needs and methodological challenges SO DIGESTIVE DISEASES LA English DT Article DE mortality, alcohol-attributable; health consequences, alcohol; alcohol abuse ID CORONARY-HEART-DISEASE; POPULATION HEALTH; AVERAGE VOLUME; UNITED-STATES; MORTALITY; DRINKING; RISK; METAANALYSIS; MORBIDITY; PATTERNS AB Background/Aims: Extensive research has shown that alcohol consumption leads to poor health and premature death through its causal or contributing roles in numerous chronic health conditions and acute health outcomes, including various cancers, liver disease, and injuries. Paradoxically, advances in understanding of the causal associations between alcohol consumption and various conditions have complicated our ability to discern trends in the health consequences of alcohol consumption over time. Methods: Four distinct needs for information on alcohol's role in causing adverse health outcomes are identified. Estimates of alcohol-attributable mortality from two US studies are compared and differences identified. Results: Differences in the conditions included and alcohol-attributable fractions employed accounted for large differences in the estimated alcohol-attributable mortality for several health outcomes. Conclusion: Despite the broad consensus on many health consequences of alcohol consumption, further research is needed to clarify the conditions that are caused by alcohol consumption, magnitudes of causal relationships, and effects of different patterns of consumption and individual characteristics. Comparisons over time are needed to identify areas where improvements in public health may be occurring or are most needed, to support evaluation of specific interventions, and to encourage the public awareness of alcohol problems that is necessary to change attitudes and behaviors involving alcohol consumption. Copyright (C) 2005 S. Karger AG, Basel. C1 NIAAA, Div Epidemiol & Prevent Res, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bloss, G (reprint author), NIAAA, Div Epidemiol & Prevent Res, NIH, US Dept Hlth & Human Serv, 5635 Fishers Lane,Room 2075, Bethesda, MD 20892 USA. EM gbloss@mail.nih.gov NR 33 TC 5 Z9 5 U1 1 U2 11 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-2753 J9 DIGEST DIS JI Dig. Dis. PY 2005 VL 23 IS 3-4 BP 162 EP 169 DI 10.1159/000090162 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 015WT UT WOS:000235582700002 PM 16508279 ER PT J AU Tomkowicz, B Singh, SP Lai, DS Singh, A Mahalingham, S Joseph, J Srivastava, S Srinivasan, A AF Tomkowicz, B Singh, SP Lai, DS Singh, A Mahalingham, S Joseph, J Srivastava, S Srinivasan, A TI Mutational analysis reveals an essential role for the LXXLL motif in the transformation function of the human herpesvirus-8 oncoprotein, Kaposin SO DNA AND CELL BIOLOGY LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; PROTEIN-COUPLED RECEPTOR; DNA-SEQUENCES; NUCLEAR-RECEPTOR; GLUCOCORTICOID-RECEPTOR; ENDOTHELIAL-CELLS; MULTIPLE LOCI; KSHV; VIRUS; GENE AB Human herpesvirus-8 (HHV-8) is causally linked to Kaposi's sarcoma (KS). Sequence analysis of the genome and subsequent studies revealed several genes including kaposin, with transformation properties in cell culture. In this study, we have analyzed the requirement of Kaposin A for cellular transformation in an effort to understand its contribution towards KS pathogenesis. Comparative analysis of Kaposin with other proteins identified the LXXLL motif spanning from residues 31 - 35 (LVCLL). The observation that the LXXLL motif is present in nuclear receptor coactivators that mediate the interaction of coactivators with nuclear receptors has prompted us to investigate the relevance of this motif for Kaposin's function(s). Kaposin A coding sequences were cloned into a eukaryotic expression plasmid with the Flag (FL) epitope fused in-frame at the C-terminus (Kap-FL). To evaluate the role of leucine residues in the motif, site-directed mutagenesis was utilized, whereby alanine was substituted for the leucine residues (Kap-AXXAA-FL). Both Kap-FL and Kap-AXXAA-FL exhibited similar levels of expression in cells. Interestingly, the Kap-AXXAA-FL mutant failed to show transforming activity by two independent assays: anchorage-independent growth, and focus formation. Immunofluorescence (IFA) and FACS analysis indicated that Kap-FL was localized around the nucleus and at the cell surface, respectively. However, Kap-AXXAA-FL exhibited diffuse cytoplasmic staining as measured by IFA yet was still detectable on the cell surface by FACS. Ironically, both Kap-FL and Kap-AXXAA-FL were able to activate the AP-1 promoter. These results support an important role for the LXXLL motif in the ability of Kaposin to induce transformation. C1 Thomas Jefferson Univ, Dept Microbiol & Immunol, Kimmel Canc Inst, Philadelphia, PA 19107 USA. NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. Ctr DNA Fingerprinting & Diagnost, Hyderabad 500076, Andhra Pradesh, India. USUHS, Ctr Prostate Dis Res, Dept Surg, Rockville, MD USA. RP Srinivasan, A (reprint author), Thomas Jefferson Univ, Dept Microbiol & Immunol, Kimmel Canc Inst, 1020 Locust St,JAH Rm 461, Philadelphia, PA 19107 USA. EM alagarsamy.srinivasan@mail.tju.edu FU NCI NIH HHS [CA99914]; NIAID NIH HHS [AI29306, T32AI07492]; PHS HHS [T3209678] NR 54 TC 13 Z9 13 U1 0 U2 2 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD JAN PY 2005 VL 24 IS 1 BP 10 EP 20 DI 10.1089/dna.2005.24.10 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 886GQ UT WOS:000226215300002 PM 15684715 ER PT J AU Minneci, PC Deans, KJ Haley, M Cui, XZ Natanson, C Eichacker, PQ AF Minneci, Peter C. Deans, Katherine J. Haley, Michael Cui, Xizhong Natanson, Charles Eichacker, Peter Q. BE Gad, SC TI FACTORS INFLUENCING THE EFFICACY OF MEDIATOR-SPECIFIC ANTI-INFLAMMATORY, GLUCOCORTICOID, AND ANTICOAGULANT THERAPIES FOR SEPSIS SO DRUG DISCOVERY HANDBOOK SE Pharmaceutical Development Series LA English DT Article; Book Chapter ID TUMOR-NECROSIS-FACTOR; PLACEBO-CONTROLLED TRIAL; INTERLEUKIN-1 RECEPTOR ANTAGONIST; FACTOR PATHWAY INHIBITOR; RANDOMIZED CONTROLLED-TRIAL; ACTIVATING-FACTOR ACETYLHYDROLASE; INFLAMMATORY RESPONSE SYNDROME; HIGH-DOSE METHYLPREDNISOLONE; CONTROLLED MULTICENTER TRIAL; FACTOR ANTIBODY-FRAGMENT C1 [Minneci, Peter C.; Deans, Katherine J.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Minneci, Peter C.; Deans, Katherine J.; Haley, Michael; Cui, Xizhong; Natanson, Charles; Eichacker, Peter Q.] Massachusetts Gen Hosp, Dept Chem, Boston, MA 02114 USA. RP Minneci, PC (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NR 112 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-47172-878-8 J9 PHARM DEV PY 2005 BP 937 EP 959 DI 10.1002/0471728780.ch20 D2 10.1002/0471728780 PG 23 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BYH31 UT WOS:000298786800022 ER PT J AU Berger, VW AF Berger, VW TI A novel criterion for selecting covariates SO DRUG INFORMATION JOURNAL LA English DT Article DE confounding; covariate adjustment; ranking and selection; selection bias; Simpson's paradox ID BASE-LINE COMPARISONS; CLINICAL-TRIALS; CATEGORICAL-DATA; ADJUSTMENT; RANDOMIZATION; IMBALANCE; BALANCE; BIAS AB Through a combination of bad luck and possibly selection bias, imbalances in prognostic baseline variables across treatment groups have plagued many randomized clinical trials. It is common, in practice, to test for imbalances and adjust for variables observed to be sufficiently unbalanced at baseline. Yet, the literature condemns these practices on the grounds that imbalances are necessarily random when observed in the context of a randomized trial (hence, testing is illogical), and suggests that all prognostic covariates, unbalanced or not, should be included in the model used for analysis. When there are a large number of covariates relative to the sample size, decisions need to be made regarding which covariates to actually include in a suitably parsimonious model. Proponents of the approach to model-building by testing for baseline imbalances might suggest reaching these decisions by considering the degree of imbalance of each covariate; those that criticize this approach might instead consider the ability of the covariate to predict the outcome of interest. Some hybrid approaches have been explored as well. We introduce a criterion that allows for the specification of an optimal hybrid approach. C1 NCI, Bethesda, MD 20892 USA. Univ Maryland Baltimore Cty, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), NCI, EPN 3131,6130 Execut Blvd,MSC 7354, Bethesda, MD 20892 USA. EM vb78c@nih.gov NR 25 TC 2 Z9 2 U1 0 U2 2 PU DRUG INFORMATION ASSOCIATION PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2005 VL 39 IS 3 BP 233 EP 241 PG 9 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 954FX UT WOS:000231140600003 ER PT J AU Lafite, P Macherey, AC Dijols, S Dansette, PM Zeldin, DC Mansuy, D AF Lafite, P Macherey, AC Dijols, S Dansette, PM Zeldin, DC Mansuy, D TI Selective inhibition of human CYP 2J2 by ebastine analogs SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 9th European ISSX Meeting CY JUN 12-17, 2005 CL Nice, FRANCE C1 Univ Paris 05, CNRS, UMR8601, Paris, France. NIEHS, Lab Pulm Pathol, Res Triangle Pk, NC 27709 USA. RI DANSETTE, Patrick/B-8384-2014; Lafite, Pierre/F-6806-2011 OI Lafite, Pierre/0000-0003-1637-4966 NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2005 VL 37 SU 1 MA 44 BP 21 EP 21 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 973PP UT WOS:000232535400045 ER PT J AU Belsky, J Booth-LaForce, CL Bradley, R Brownell, CA Burchinal, M Campbell, SB Clarke-Stewart, KA Friedman, SL Hirsh-Pasek, K Huston, A Jaeger, E Johnson, DJ Kelly, JF Knoke, B Marshall, N McCartney, K O'Brien, M Owen, MT Payne, C Pianta, R Randolph, SM Robeson, W Spieker, S Vandell, DL Weinraub, M AF Belsky, J Booth-LaForce, CL Bradley, R Brownell, CA Burchinal, M Campbell, SB Clarke-Stewart, KA Friedman, SL Hirsh-Pasek, K Huston, A Jaeger, E Johnson, DJ Kelly, JF Knoke, B Marshall, N McCartney, K O'Brien, M Owen, MT Payne, C Pianta, R Randolph, SM Robeson, W Spieker, S Vandell, DL Weinraub, M CA Natl Inst Child Hlth Human Dev TI A day in third grade: A large-scale study of classroom quality and teacher and student behavior SO ELEMENTARY SCHOOL JOURNAL LA English DT Article ID CHILD-CARE; CLASS SIZE; KINDERGARTEN; PREDICTORS; SCHOOLS AB Observations of 780 third-grade classrooms described classroom activities, child-teacher interactions, and dimensions of the global classroom environment, which were examined in relation to structural aspects of the classroom and child behavior. 1 child per classroom was targeted for observation in relation to classroom quality and teacher and child behavior. These children were enrolled in the ongoing NICHD Study of Early Child Care and Youth Development: 80% of the sample was Caucasian, 22% had a family income-to-needs ratio of 2.0 or less, and 26% of mothers had a high school education or less. Classrooms were observed for a minimum of eight, 30-minute cycles over the course of the day, beginning at the start of the school day, with an intention of observing during academic instruction time. Time samplings of activities, teacher behaviors, and child behaviors as well as global ratings of the classroom environment were obtained. The most frequently observed forms of activity were whole-group instruction or individual seatwork. As expected, the largest portion of time was allocated to literacy-related activities. By a ratio of nearly 11:1, instructional activities (across any content area) were basic-skill-focused versus focused on analysis/inference or synthesis of information. There was wide variation in the frequency of most activities across classrooms. Global ratings also demonstrated significant variability across classrooms. Global and time-sampled codes of teacher behavior and classroom climate were only slightly related to a range of structural factors, such as class size, child-teacher ratio, or teacher experience. Students' engagement in academic activities was higher when classrooms provided more instructional and emotional support. From first to third grade, global aspects of the classroom, such as positive climate or teacher sensitivity, had significant but low stability; time devoted to literacy or math activities was uncorrelated across the two grade levels. These findings suggest that third grade is a highly variable context for children in the United States with a strong emphasis on learning basic skills and that structural factors, such as class size and teacher education and experience, show little relation to the experiences of children in classrooms. C1 NICHD, CRMC, Early Child Care Res Network, Rockville, MD 20852 USA. RP Belsky, J (reprint author), NICHD, CRMC, Early Child Care Res Network, 6100 Execut Blvd,4B05, Rockville, MD 20852 USA. RI Marshall, Nancy/C-3428-2012 NR 38 TC 0 Z9 0 U1 3 U2 9 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0013-5984 J9 ELEM SCHOOL J JI Elem. Sch. J. PD JAN PY 2005 VL 105 IS 3 BP 305 EP 323 PG 19 WC Education & Educational Research SC Education & Educational Research GA 888KF UT WOS:000226372100004 ER PT J AU Zhang, MD Sun, XD Mark, SD Chen, W Wong, L Dawsey, SM Qiao, YL Fraumeni, JF Taylor, PR O'Brien, TR AF Zhang, MD Sun, XD Mark, SD Chen, W Wong, L Dawsey, SM Qiao, YL Fraumeni, JF Taylor, PR O'Brien, TR TI Hepatitis C virus infection, Linxian, China SO EMERGING INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 11th International Symposium on Viral Hepatitis and Liver Disease CY APR 06-10, 2003 CL Sydney, AUSTRALIA ID COMMERCIAL PLASMA DONORS; RISK-FACTORS; HEPATOCELLULAR-CARCINOMA; EASTERN CHINA; PREVALENCE; POPULATION; EGYPT; COMMUNITY AB Bloodborne viruses may have spread in rural China during the past 25 years, but population-based prevalence estimates are lacking. We examined the frequency of hepatitis C virus (HCV) and HIV type 1 (HIV-1) among residents of Linxian, a rural community in Henan Province. In 2000, blood was collected from participants ( 55 years of age) who had enrolled in a population-based nutritional intervention trial in 1985. We randomly selected 500 participants for HCV testing and 200 participants for HIV-1 testing. For HCV, 48 (9.6%) of 500 participants were positive by enzyme immunoassay and recombinant immunoblot assay (95% confidence interval, 7.0%-12.2%), and prevalence was lowest in the most geographically isolated participants. Among the HCV-infected participants, 42 had a specimen available from 1985, of which 16 (38.1%) were positive for HCV. For HIV-1, 0/200 participants were positive. We conclude that HCV is now a common infection among older adults in Linxian, China. C1 NIH, Baltimore, MD USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. RP O'Brien, TR (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7082, Rockville, MD 20852 USA. EM obrient@exchange.nih.gov RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 FU NCI NIH HHS [N01 CO 12400, N01 SC 91030, N01CO12400] NR 27 TC 21 Z9 24 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 PY 2005 VL 11 IS 1 BP 17 EP 21 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 885HI UT WOS:000226147300004 PM 15705317 ER PT J AU Stratakis, CA Rennert, OM AF Stratakis, CA Rennert, OM TI Turner syndrome - An update SO ENDOCRINOLOGIST LA English DT Review DE Turner syndrome; genetics; adult patients; phenotype; genotype ID BONE-MINERAL DENSITY; CONGENITAL HEART-DISEASE; Y-CHROMOSOME SEQUENCES; CARDIOVASCULAR RISK-FACTORS; GROWTH-HORMONE TREATMENT; X-CHROMOSOME; FINAL HEIGHT; PARENTAL ORIGIN; ESTROGEN REPLACEMENT; LIVER ABNORMALITIES AB It has been 10 years since our last review on Turner syndrome for The Endocrinologist. At the time, we focused on the recognition of this condition and the understanding, in the last 50 years, of its many clinical sequelae, starting from what Dr Turner had described; we also noted the first steps that the Genome Project had undertaken towards the molecular elucidation of the condition. As it befits any genetic condition in the early 21st century, the issues of the current review are quite different: the then-experimental treatment with recombinant growth hormone (rGH) is now approved and considered standard of practice (albeit not without significant controversy); patients with Turner syndrome, treated and untreated with rGH, are getting older, have entered the workforce, and have families of their own, and, thus, a previously unstudied phenotype emerges, that of the older adult with complete or partial chromosome X monosomy; and, finally, significant advances have been made in the molecular understanding of the condition that go well beyond chromosomal studies. The molecular biology of the X chromosome holds promise for the elucidation of such important and complex questions as what determines gender (and to some extent, perhaps, sexual identity), ovarian function (and, consequently, reproduction); processes such as skeletal maturation, proportions, and final height; and many other biologic parameters that are known to demonstrate X-linked differences. C1 NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NICHHD, Lab Clin Genom, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHD, Sect Endocrinol & Genet, DEB, NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC 1862, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov NR 111 TC 6 Z9 7 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD JAN-FEB PY 2005 VL 15 IS 1 BP 27 EP 36 DI 10.1097/01.ten.0000152836.30636.a7 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 893QN UT WOS:000226734400008 ER PT J AU Herkenham, M AF Herkenham, M TI Folliculo-stellate (FS) cells of the anterior pituitary mediate interactions between the endocrine and immune systems SO ENDOCRINOLOGY LA English DT Editorial Material ID LIPOPOLYSACCHARIDE; COMMUNICATION; INTERLEUKIN-6; HORMONE; GLAND; LOCALIZATION; ACTIVATION; SECRETION; RELEASE; PATHWAY C1 NIMH, Funct Neuroanat Sect, NIH, Bethesda, MD 20892 USA. RP Herkenham, M (reprint author), NIMH, Funct Neuroanat Sect, NIH, Bldg 35,Room 1C913, Bethesda, MD 20892 USA. EM herkenh@mail.nih.gov OI Herkenham, Miles/0000-0003-2228-4238 NR 21 TC 14 Z9 15 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2005 VL 146 IS 1 BP 33 EP 34 DI 10.1210/en.2004-1269 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 880CN UT WOS:000225766500007 PM 15601904 ER PT J AU Walker, NJ Crockett, PW Nyska, A Brix, AE Jokinen, MP Sells, DM Hailey, JR Easterling, M Haseman, JK Yin, M Wyde, ME Bucher, JR Portier, CJ AF Walker, NJ Crockett, PW Nyska, A Brix, AE Jokinen, MP Sells, DM Hailey, JR Easterling, M Haseman, JK Yin, M Wyde, ME Bucher, JR Portier, CJ TI Dose-additive carcinogenicity of a defined mixture of "dioxin-like compounds" SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE carcinogenicity; dioxin; mixtures; PCBs; persistent organochlorine pollutants; polychlorinated bipheryls; POPs; risk assessment; TEF; toxic equivalency factor ID TOXIC EQUIVALENCY FACTORS; CYP1A2 ENZYME-ACTIVITY; FACTORS TEFS; DIBENZOFURANS; PCBS; BIPHENYLS; PCDFS; PCDDS; LIVER; RATS AB Use of the dioxin toxic equivalency factor (TEF) approach in human risk assessments assumes that the combined effects of dioxin-like compounds in a mixture can be predicted based on a potency-adjusted dose-additive combination of constituents of the mixture. In this study, we evaluated the TEF approach in experimental 2-year rodent cancer bioassays with female Harlan Sprague-Dawley rats receiving 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5-pentachlorobiphenyl (PCB-126), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), or a mixture of the three compounds. Statistically based dose-response modeling indicated that the shape of the dose-response curves for hepatic, lung, and oral mucosal neoplasms was the same in studies of the three individual chemicals and the mixture. In addition, the dose response for the mixture could be predicted from a combination of the potency-adjusted doses of the individual compounds. Finally, we showed that use of the current World Health Organization dioxin TEF values adequately predicted the increased incidence of liver tumors (hepatocellular adenoma and cholangiocarcinoma) induced by exposure to the mixture. These data support the use of the TEF approach for dioxin cancer risk assessments. C1 Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27705 USA. Constella Grp, Res Triangle Pk, NC USA. A Charles River Co, Pathol Associates, Durham, NC USA. Expt Pathol Labs, Res Triangle Pk, NC USA. Battelle Columbus Labs, Columbus, OH USA. RP Walker, NJ (reprint author), Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, 111 Alexander Dr, Res Triangle Pk, NC 27705 USA. EM walker3@niehs.nih.gov RI Portier, Christopher/A-3160-2010; Walker, Nigel/D-6583-2012 OI Portier, Christopher/0000-0002-0954-0279; Walker, Nigel/0000-0002-9111-6855 NR 17 TC 63 Z9 67 U1 0 U2 9 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2005 VL 113 IS 1 BP 43 EP 48 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 885ZQ UT WOS:000226196300028 PM 15626646 ER PT J AU De Roos, AJ Blair, A Rusiecki, JA Hoppin, JA Svec, M Dosemeci, M Sandler, DP Alavanja, MC AF De Roos, AJ Blair, A Rusiecki, JA Hoppin, JA Svec, M Dosemeci, M Sandler, DP Alavanja, MC TI Cancer incidence among glyphosate-exposed pesticide applicators in the agricultural health study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cancer; cohort study; farming; glyphosate; pesticide ID NON-HODGKINS-LYMPHOMA; MULTIPLE-MYELOMA; HERBICIDE GLYPHOSATE; IN-VITRO; ACTIVE INGREDIENT; MICRONUCLEUS TEST; RISK-FACTORS; LIFE-STYLE; ROUNDUP; MUTAGENICITY AB Glyphosate is a broad-spectrum herbicide that is one of the most frequently applied pesticides in the world. Although there has been little consistent evidence of genotoxicity or carcinogenicity from in vitro and animal studies, a few epidemiologic reports have indicated potential health effects of glyphosate. We evaluated associations between glyphosate exposure and cancer incidence in the Agricultural Health Study (AHS), a prospective cohort study of 57,311 licensed pesticide applicators in Iowa and North Carolina. Detailed information on pesticide use and other factors was obtained from a self-administered questionnaire completed at time of enrollment (1993-1997). Among private and commercial applicators, 75.5% reported having ever used glyphosate, of which > 97% were men. In this analysis, glyphosate exposure was defined as a) ever personally mixed or applied products containing glyphosate; b) cumulative lifetime days of use, or "cumulative exposure days" (years of use X days/year); and c) intensity-weighted cumulative exposure days (years of use X days/year X estimated intensity level). Poisson regression was used to estimate exposure-response relations between glyphosate and incidence of all cancers combined and 12 relatively common cancer subtypes. Glyphosate exposure was not associated with cancer incidence overall or with most of the cancer subtypes we studied. There was a suggested association with multiple myeloma incidence that should be followed up as more cases occur in the AHS. Given the widespread use of glyphosate, future analyses of the AHS will allow further examination of long-term health effects, including less common cancers. C1 Univ Washington, Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98109 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98109 USA. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Natl Inst Environm Hlth Sci, Program Epidemiol, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP De Roos, AJ (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Program Epidemiol, 1100 Fairview Ave N,M4-B874, Seattle, WA 98109 USA. EM deroos@u.washington.edu OI Sandler, Dale/0000-0002-6776-0018 NR 56 TC 77 Z9 85 U1 9 U2 70 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2005 VL 113 IS 1 BP 49 EP 54 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 885ZQ UT WOS:000226196300029 PM 15626647 ER PT J AU Goehl, TJ AF Goehl, TJ TI Giving a voice to environmental health research SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Goehl, TJ (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM goehl@niehs.nih.gov NR 9 TC 0 Z9 0 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PY 2005 SI SI BP 64 EP 69 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 910TW UT WOS:000227956100008 ER PT J AU Huang, LS Cox, C Myers, GJ Davidson, PW Cernichiari, E Shamlaye, CF Sloane-Reeves, J Clarkson, TW AF Huang, LS Cox, C Myers, GJ Davidson, PW Cernichiari, E Shamlaye, CF Sloane-Reeves, J Clarkson, TW TI Exploring nonlinear association between prenatal methylmercury exposure from fish consumption and child development: evaluation of the Seychelles Child Development Study nine-year data using semiparametric additive models SO ENVIRONMENTAL RESEARCH LA English DT Article DE child development; fish consumption; generalized additive models; methylmercury; serniparametric models ID IN-UTERO EXPOSURE; NEURODEVELOPMENTAL OUTCOMES; FETAL METHYLMERCURY; DIET; MERCURY; AGE; MILESTONES; POPULATION AB Studies of the association between prenatal methylmercury exposure from maternal fish consumption and neurodevelopmental test scores in the Seychelles Child Development Study have not found adverse effects through age 9 years. The analysis for the most recent 9-year data (Lancet 361 (2003) 1686) employed conventional linear regression models. In this study we reanalyzed the same Seychelles 9-year data using semiparametric additive models with different degrees of smoothing to explore whether nonlinear effects of prenatal exposure were present. Of 21 endpoints in the linear analysis, we chose only those with a two-tailed P value less than 0.2 for the effect of prenatal exposure. Six endpoints met the criterion. A nonlinear effect was identified with the more smooth model for only one endpoint. The test for an overall effect of prenatal exposure was also significant, with a P value of 0.04, while the corresponding P value in the linear regression analysis was 0.08. The nonlinear curve appeared to be nearly flat when the level was below approximately 12 ppm in maternal hair, with a linear trend above that level, suggesting a possible adverse effect in the uppermost range of prenatal exposure included in this cohort. Because of the descriptive nature of semiparametric additive models, the P values are not precise, and certainly there are fewer data above 12 ppm. We conclude that this reanalysis supports the primary linear analysis, showing little evidence for a prenatal adverse effect. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Rochester, Ctr Med, Dept Biostat & Computat Biol, Sch Med & Dent, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. NICHD, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bethesda, MD 20892 USA. Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Environm Med, Rochester, NY 14642 USA. Minist Hlth, Victoria, Mahe, Seychelles. RP Huang, LS (reprint author), Univ Rochester, Ctr Med, Dept Biostat & Computat Biol, Sch Med & Dent, 601 Elmwood Ave,Box 630, Rochester, NY 14642 USA. EM lhuang@bst.rochester.edu RI Myers , Gary /I-4901-2013 OI Myers , Gary /0000-0003-4317-015X FU NIEHS NIH HHS [ES-01247, R01-ES10219, T32 ES-007271]; PHS HHS [R01-08442] NR 36 TC 17 Z9 18 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD JAN PY 2005 VL 97 IS 1 BP 100 EP 108 DI 10.1016/j.envres.2004.05.004 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 866SC UT WOS:000224792300012 PM 15476739 ER PT J AU Hatch, M Ron, E Bouville, A Zablotska, L Howe, G AF Hatch, M Ron, E Bouville, A Zablotska, L Howe, G TI The Chernobyl disaster: Cancer following the accident at the Chernobyl nuclear power plant SO EPIDEMIOLOGIC REVIEWS LA English DT Article ID CHILDHOOD THYROID CARCINOMAS; IN-UTERO EXPOSURE; POST-CHERNOBYL; INFANT LEUKEMIA; RADIATION RISKS; HIGH PREVALENCE; PAPILLARY CARCINOMAS; EXTERNAL RADIATION; RUSSIAN-FEDERATION; EMERGENCY WORKERS C1 NCI, Chernobyl Res Unit, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet,NIH,Dept Hlth & Human, Rockville, MD 20852 USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. RP Hatch, M (reprint author), NCI, Chernobyl Res Unit, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet,NIH,Dept Hlth & Human, 6120 Execut Blvd, Rockville, MD 20852 USA. EM hatchm@mail.nih.gov NR 93 TC 51 Z9 51 U1 0 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X EI 1478-6729 J9 EPIDEMIOL REV JI Epidemiol. Rev. PY 2005 VL 27 BP 56 EP 66 DI 10.1093/epirev/mxi012 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 939KR UT WOS:000230072100008 PM 15958427 ER PT J AU Wacholder, S AF Wacholder, S TI The impact of a prevention effort on the community SO EPIDEMIOLOGY LA English DT Editorial Material ID LUNG-CANCER; ATTRIBUTABLE RISK; WOMEN; EXPOSURE AB Commonly used measures of the impact of an exposure on disease are inadequate for assessing the potential benefit of community-based efforts to prevent disease caused by the exposure in question. Because relative measures of effect, including the risk ratio, odds ratio, and population attributable risk (PAR) do not account for the absolute risk of disease, they lack the most crucial element for evaluating the opportunity for prevention of disease caused by the exposure. Attributable community risk (ACR), defined as the difference between the crude risk (or overall risk in the population) and the risk in the unexposed, better captures the potential impact of a prevention effort. PAR can be expressed as the proportion of the disease incidence in a population that is attributable to the exposure. ACR, by contrast, is the proportion of the population that is affected with the disease due to the exposure. Therefore, unlike PAR, risk ratio or odds ratio, ACR is useful for comparing the potential benefit of programs aimed at the prevention of different diseases. For example, ACR provides a useful comparison of the potential benefits of efforts to prevent breast cancer and to prevent ovarian cancer among women with a BRCA1 or BRCA2 mutation. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Wacholder, S (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM Wacholder@NIH.gov NR 13 TC 27 Z9 27 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 2005 VL 16 IS 1 BP 1 EP 3 DI 10.1097/01.ede.0000147633.09891.16 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 884JA UT WOS:000226079600001 PM 15613938 ER PT J AU Schisterman, EF Perkins, NJ Liu, A Bondell, H AF Schisterman, EF Perkins, NJ Liu, A Bondell, H TI Optimal cut-point and its corresponding youden index to discriminate individuals using pooled blood samples SO EPIDEMIOLOGY LA English DT Article ID CHARACTERISTIC ROC CURVES; ESTIMATING PREVALENCE; ASSESSMENTS; BIOMARKERS; ACCURACY; DISEASE AB Costs can hamper the evaluation of the effectiveness of new biomarkers. Analysis of smaller numbers of pooled specimens has been shown to be a useful cost-cutting technique. The Youden index (J), a function of sensitivity (q) and specificity (p), is a commonly used measure of overall diagnostic effectiveness. More importantly, J is the maximum vertical distance or difference between the ROC curve and the diagonal or chance line; it occurs at the cut-point that optimizes the biomarker's differentiating ability when equal weight is given to sensitivity and specificity. Using the additive property of the gamma and normal distributions, we present a method to estimate the Youden index and the optimal cut-point, and extend its applications to pooled samples. We study the effect of pooling when only a fixed number of individuals are available for testing, and pooling is carried out to save on the number of assays. We measure loss of information by the change in root mean squared error of the estimates of the optimal cut-point and the Youden index, and we study the extent of this loss via a simulation study. In conclusion, pooling can result in a substantial cost reduction while preserving the effectiveness of estimators, especially when the pool size is not very large. C1 NICHHD, NICHD, Div Epidemiol Stat & Prevent Res, NIH,DHHS, Bethesda, MD 20852 USA. American Univ, Dept Math & Stat, Washington, DC 20016 USA. Rutgers State Univ, Dept Stat, Piscataway, NJ USA. RP Schisterman, EF (reprint author), NICHHD, NICHD, Div Epidemiol Stat & Prevent Res, NIH,DHHS, 6100 Execut Blvd, Bethesda, MD 20852 USA. EM schistee@mail.nih.gov OI Perkins, Neil/0000-0002-6802-4733; Liu, Aiyi/0000-0002-6618-5082; Schisterman, Enrique/0000-0003-3757-641X NR 19 TC 298 Z9 303 U1 1 U2 11 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 2005 VL 16 IS 1 BP 73 EP 81 DI 10.1097/01.ede.0000147512.81966.ba PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 884JA UT WOS:000226079600011 PM 15613948 ER PT J AU Daniels, JL Longnecker, MP Rowland, AS Golding, J AF Daniels, JL Longnecker, MP Rowland, AS Golding, J TI Measuring mercury concentration SO EPIDEMIOLOGY LA English DT Letter C1 Univ N Carolina, Chapel Hill, NC 27514 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Univ Bristol, Bristol, Avon, England. RP Daniels, JL (reprint author), Univ N Carolina, Chapel Hill, NC 27514 USA. EM julie_daniels@unc.edu NR 4 TC 0 Z9 0 U1 1 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 2005 VL 16 IS 1 BP 134 EP 134 DI 10.1097/01.ede.0000147361.21851.3f PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 884JA UT WOS:000226079600025 ER PT J AU Theodore, WH Juhasz, C Savic, V Drevets, W AF Theodore, WH Juhasz, C Savic, V Drevets, W TI Serotonin, depression, and epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 NINDS, NIH, Bethesda, MD 20892 USA. Wayne State Univ, Sch Med, Detroit, MI 48202 USA. Karolinska Inst, Stockholm, Sweden. NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 3 EP 3 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540100009 ER PT J AU Rogawski, MA AF Rogawski, MA TI Neurosteroids and brain excitability SO EPILEPSIA LA English DT Meeting Abstract CT 26th International Epilepsy Congress CY AUG 28-SEP 01, 2005 CL Paris, FRANCE SP Int League Against Epilepsy, Int Bureau Epilepsy C1 NIH, Epilepsy Res Sect, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 6 BP 11 EP 11 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 964MN UT WOS:000231885300034 ER PT J AU Gaillard, WD AF Gaillard, WD TI Imaging pediatric functional and structural anatomy with MRI SO EPILEPSIA LA English DT Meeting Abstract CT 26th International Epilepsy Congress CY AUG 28-SEP 01, 2005 CL Paris, FRANCE SP Int League Against Epilepsy, Int Bureau Epilepsy C1 George Washington Univ, Childrens Natl Med Ctr, Dept Neurosci, Washington, DC USA. NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 6 BP 27 EP 27 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 964MN UT WOS:000231885300093 ER PT J AU Theodore, WH AF Theodore, WH TI Can we image epileptogenesis? SO EPILEPSIA LA English DT Meeting Abstract CT 26th International Epilepsy Congress CY AUG 28-SEP 01, 2005 CL Paris, FRANCE SP Int League Against Epilepsy, Int Bureau Epilepsy C1 NIH, Clin Epilepsy Sect, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 6 BP 27 EP 27 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 964MN UT WOS:000231885300094 ER PT J AU Boudreau, EA Liow, K Frattali, TM Wiggs, E Turner, JT Feuillan, J Sato, S Patsalides, B Patronas, N Biesecker, LG Theodore, WH AF Boudreau, EA Liow, K Frattali, TM Wiggs, E Turner, JT Feuillan, J Sato, S Patsalides, B Patronas, N Biesecker, LG Theodore, WH TI Hypothalamic hamartomas and seizures: Distinct natural history of isolated and Pallister-Hall syndrome cases SO EPILEPSIA LA English DT Article DE hypothalamic hamartoma; Pallister-Hall syndrome; precocious puberty ID GELASTIC SEIZURES; PRECOCIOUS PUBERTY; TUBER CINEREUM; GROWTH-HORMONE; LAUGHTER; EPILEPSY AB Purpose: Hypothalamic hamartomas (HHs) have been associated with uncontrolled seizures, and aggressive therapy including surgery is often recommended. However, some patients, particularly those with other findings associated with Pallister-Hall syndrome (PHS), have a more benign course. Methods: Thirty-seven of 40 PHS patients and 16 of 16 patients with isolated HH had a lesion confirmed on magnetic resonance imaging (MRI). Records for all patients were reviewed for the following information: presence of seizures, age at seizure onset, seizure type, seizure frequency, number of antiepileptic medications (AEDs) at the time of evaluation, past AEDs, MRI characteristics of the HH, presence of endocrine dysfunction, and presence of developmental and behavioral problems. Results: All isolated HH patients had a history of seizures, compared with 13 of 40 PHS patients (all PHS patients with seizures had hamartomas). In isolated HH, seizures started earlier in life, occurred more frequently, and were harder to control than those in patients with PHS. Isolated HH patients were more likely to have behavioral and developmental problems than were PHS patients. The T-2 signal of the hamartoma was isointense to gray matter in the majority of PHS patients, but showed a significant increase in all but one patient with isolated HH. Conclusions: Patients with isolated HH have a distinct clinical phenotype, showing more severe seizures and neurologic dysfunction, HH showing increased T-2 signal, and are more likely to have precocious puberty. In contrast, PHS patients usually have well-controlled seizures and other endocrine disturbances than precocious puberty. Patients with HH with or without seizures should be evaluated carefully for other clinical manifestations of PHS, particularly before surgery is considered. C1 Natl Inst Neurol Disorders & Stroke, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, EEG & Sleep Sect, Bethesda, MD 20892 USA. Warren G Magnuson Clin Ctr, Speech Language Pathol Sect, Bethesda, MD USA. Warren G Magnuson Clin Ctr, Rehabil Med Dept, Bethesda, MD USA. Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD USA. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Theodore, WH (reprint author), Natl Inst Neurol Disorders & Stroke, Clin Epilepsy Sect, NIH, 10 Ctr Dr,Bldg 10,Room 5N250,MSC 1408, Bethesda, MD 20892 USA. EM Theodorw@ninds.nih.gov NR 29 TC 25 Z9 25 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JAN PY 2005 VL 46 IS 1 BP 42 EP 47 DI 10.1111/j.0013-9580.2005.68303.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 894RT UT WOS:000226810000006 PM 15660767 ER PT J AU Moore, EN Berl, MM Ritzl, EK Cho, YW Weber, D Pearl, PL Weinstein, SL Conry, JA Sato, S Theodore, WH Gaillard, WD AF Moore, EN Berl, MM Ritzl, EK Cho, YW Weber, D Pearl, PL Weinstein, SL Conry, JA Sato, S Theodore, WH Gaillard, WD TI Association between epilepsy etiology and atypical language dominance assessed by a panel of fMRI tasks SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 53 EP 54 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540100158 ER PT J AU Cho, YW Moore, EN Bonwetsch, R Ritzl, EK Birn, R Luh, WM Gaillard, WD Theodore, WH AF Cho, YW Moore, EN Bonwetsch, R Ritzl, EK Birn, R Luh, WM Gaillard, WD Theodore, WH TI Pulsed arterial spin labeling mr imaging in temporal lobe epilepsy: A comparison with O-15-H2O pet SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 Keimyung Univ, Dongsan Med Ctr, Taegu, South Korea. NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 54 EP 54 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540100160 ER PT J AU Kaminski, RM Marini, H Ortinski, PI Yonekawa, W Vicini, S Rogawski, MA AF Kaminski, RM Marini, H Ortinski, PI Yonekawa, W Vicini, S Rogawski, MA TI Androstenol (5 alpha-androst-16-en-3 alpha-ol) - A novel neurosteroid? SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 NINDS, Epilepsy Res Sect, Bethesda, MD 20892 USA. Univ Messina, Fac Med & Surg, AOUG Martino, I-98100 Messina, Italy. Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20057 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 109 EP 109 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540100316 ER PT J AU Gaillard, WD Weinstein, S Conry, J Pearl, PL Fazilat, S Vezina, G Revees-Tyer, P Theodore, WH AF Gaillard, WD Weinstein, S Conry, J Pearl, PL Fazilat, S Vezina, G Revees-Tyer, P Theodore, WH TI Serial (18)FDG-PET in children with partial epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 149 EP 149 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540100436 ER PT J AU Bagic, A Balish, M Bonwetsch, R Theodore, WH Heiss, JD Sato, S AF Bagic, A Balish, M Bonwetsch, R Theodore, WH Heiss, JD Sato, S TI Correlation of simultaneously recorded scalp EEG and magnetoencephalography (MEG) with invasive EEG in neurosurgical SO EPILEPSIA LA English DT Meeting Abstract CT 26th International Epilepsy Congress CY AUG 28-SEP 01, 2005 CL Paris, FRANCE SP Int League Against Epilepsy, Int Bureau Epilepsy C1 NINDS, CES, NIH, Bethesda, MD USA. NINDS, EEG Sect, NIH, Bethesda, MD USA. NINDS, Neruosurg Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 6 BP 164 EP 165 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 964MN UT WOS:000231885300599 ER PT J AU Bagic, D Balish, M Sato, S Theodore, WH Bagic, A AF Bagic, D Balish, M Sato, S Theodore, WH Bagic, A TI Civic knowledge and attitude towards epilepsy in Croatia SO EPILEPSIA LA English DT Meeting Abstract CT 26th International Epilepsy Congress CY AUG 28-SEP 01, 2005 CL Paris, FRANCE SP Int League Against Epilepsy, Int Bureau Epilepsy C1 NINDS, EEG Sect, NIH, Bethesda, MD 20892 USA. Univ Zagreb, Dept Sociol, Zagreb 41000, Croatia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 6 BP 191 EP 192 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 964MN UT WOS:000231885300702 ER PT J AU Landemberger, MC Machado, CF Mallucci, G Chesebro, B Walz, R Martins, VR AF Landemberger, MC Machado, CF Mallucci, G Chesebro, B Walz, R Martins, VR TI Cellular prion protein levels are associated with seizure threshold in null mice and transgenic strains SO EPILEPSIA LA English DT Meeting Abstract CT 26th International Epilepsy Congress CY AUG 28-SEP 01, 2005 CL Paris, FRANCE SP Int League Against Epilepsy, Int Bureau Epilepsy C1 Ludwig Inst Canc Res, Sao Paulo, Brazil. CTP Hosp Canc, Sao Paulo, Brazil. UCL Natl Hosp Neurol & Neurosurg, Inst Neurol, London WC1N 3BG, England. NIAID, Hamilton, NY USA. Univ Fed Santa Catarina, Florianopolis, SC, Brazil. RI Machado, Cleiton Fagundes/I-5907-2014; Landemberger, Michele Christine/P-3014-2014; Martins, Vilma/E-2547-2012 OI Machado, Cleiton Fagundes/0000-0002-3313-3868; Landemberger, Michele Christine/0000-0002-3513-3554; Martins, Vilma/0000-0002-2909-8502 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 6 BP 211 EP 211 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 964MN UT WOS:000231885301069 ER PT J AU Bagic, A Theodore, WH Bonwetsch, R Greenfield, J Sato, S AF Bagic, A Theodore, WH Bonwetsch, R Greenfield, J Sato, S TI Treating epilepsy with head-neck cooling without sedation SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 NINDS, EEG Sect, NIH, Bethesda, MD 20892 USA. NINDS, Clin Epidemiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 233 EP 233 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540101068 ER PT J AU Gasior, M Tang, R White, N Rogawski, MA AF Gasior, M Tang, R White, N Rogawski, MA TI Local CED infusion of botulinum toxins type A and B produces long-lasting protection against amygdala-kindled seizures in rats SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 NINDS, NIH, Epilepsy Res Sect, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 0 TC 0 Z9 0 U1 2 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 286 EP 286 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540101221 ER PT J AU White, HS Schmutz, M Pozza, M Wolf, H Stables, J Kupferberg, H AF White, HS Schmutz, M Pozza, M Wolf, H Stables, J Kupferberg, H TI The anticonvulsant profile and tolerability of rufinamide in mice and rats SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 Univ Utah, Salt Lake City, UT USA. Novartis Inst BioMed Res, Basel, Switzerland. NINDS, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 7 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 305 EP 306 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540101274 ER PT J AU Fiol, ME Hejazi, N Koul, R Xu, KE AF Fiol, ME Hejazi, N Koul, R Xu, KE TI Novel sequence variants in the glycine promoter region in Omani family with hyperekplexia SO EPILEPSIA LA English DT Meeting Abstract CT Joint Annual Meeting of the American-Epilepsy-Society/American-Clinical-Neurophsiology-Society CY DEC 02-06, 2005 CL Washington, DC SP Amer Epilepsy Soc, Amer Clin Neurophysiol Soc C1 Univ Minnesota, Minneapolis, MN 55455 USA. NIH, Neurogenet Lab, Bethesda, MD 20892 USA. Sultan Qaboos Univ, Coll Med, Muscat, Oman. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 8 BP 367 EP 367 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 973RK UT WOS:000232540101455 ER PT J AU White, S Schmutz, M Pozza, MF Franklin, MR Wolf, HH Woodhead, J Stables, J Kupferberg, HJ AF White, S Schmutz, M Pozza, MF Franklin, MR Wolf, HH Woodhead, J Stables, J Kupferberg, HJ TI Rufinamide (CGP 33101): A broad-spectrum anticonvulsant with excellent tolerability profile in rodents SO EPILEPSIA LA English DT Meeting Abstract CT 26th International Epilepsy Congress CY AUG 28-SEP 01, 2005 CL Paris, FRANCE SP Int League Against Epilepsy, Int Bureau Epilepsy C1 Univ Utah, Salt Lake City, UT USA. Novartis Inst BioMed Res, CH-4002 Basel, Switzerland. NINDS, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2005 VL 46 SU 6 BP 373 EP 373 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 964MN UT WOS:000231885302170 ER PT S AU Ye, YH AF Ye, YH BE Mayer, RJ Layfield, R TI The role of the ubiquitin-proteasome system in ER quality control SO ESSAYS IN BIOCHEMISTRY, VOL 41: THE UBIQUITIN-PROTEASOME SYSTEM SE ESSAYS IN BIOCHEMISTRY LA English DT Review; Book Chapter ID ENDOPLASMIC-RETICULUM STRESS; RECOGNIZES SUGAR CHAINS; PROTEIN-DEGRADATION; RETRO-TRANSLOCATION; MISFOLDED PROTEINS; LIGASE; MEMBRANE; CYTOSOL; COMPLEX; P97 AB Misfolded endoplasmic reticulum (ER) proteins are eliminated by the retrotranslocation pathway in eukaryotes, which is an important physiological adaptation to ER stress. This pathway can be hijacked by certain viruses to destroy folded cellular proteins, such as MHC class I heavy chain. Recent studies have highlighted the importance of the ubiquitin-proteasome system (UPS) in this process. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Ye, YH (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM yihongy@mail.nih.gov NR 45 TC 22 Z9 22 U1 0 U2 1 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON W1N 3AJ, ENGLAND SN 0071-1365 BN 1-85578-153-0 J9 ESSAYS BIOCHEM JI Essays Biochem. PY 2005 VL 41 BP 99 EP 112 DI 10.1042/EB0410099 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDG15 UT WOS:000233336000007 PM 16250900 ER PT J AU Berlin, I Vorspan, F Singleton, EG Warot, D Notides, C Heishman, SJ AF Berlin, I Vorspan, F Singleton, EG Warot, D Notides, C Heishman, SJ TI Reliability and validity of the French version of the Tobacco Craving Questionnaire SO EUROPEAN ADDICTION RESEARCH LA English DT Article DE smokers; tobacco craving; self-report questionnaire, multidimensional ID INITIAL VALIDATION; INSTRUMENT; URGE AB Objectives: ( 1) To assess the factorial structure, reliability and validity of the French language version of the Tobacco Craving Questionnaire (TCQ), a multidimensional, self-report instrument evaluating tobacco craving, to allow its use in French-speaking populations. ( 2) To compare the two different language versions of the same instrument in 2 independent samples from 2 cultures in 2 distinct time periods. Methods: The French TCQ was administered to 226 current cigarette smokers after at least 2 h of abstinence. Results: Despite the substantial difference in population characteristics between the French and American samples of smokers, both exploratory and confirmatory factor analyses indicated that the French version was best described by a 4-factor solution, similar to the original English version. Reliability estimates were 0.83, 0.79, 0.69 and 0.66 for the French and 0.82, 0.70, 0.75 and 0.48 for the English version for 'emotionality' ( factor 1), 'expectancy' ( factor 2), 'compulsivity' ( factor 3) and ` purposefulness' ( factor 4), respectively. The 4 factors accounted for 11.6, 17.1, 9.0, and 9.5% of the total variance in emotionality, expectancy, compulsivity, and purposefulness, respectively, for the French compared to 14.2, 12.5, 14.4 and 5% of the total variance for the English version, respectively. Conclusion: The French version of the TCQ is as valid and reliable instrument as the original English version and assesses the same 4 dimensions of craving for tobacco. Copyright (C) 2005 S. Karger AG, Basel. C1 CHU Pitie Salpetriere, Serv Pharmacol, FR-75013 Paris, France. Howard Univ, Ctr Drug Abuse Res, Washington, DC 20059 USA. NIDA, NIH, DHHS, Baltimore, MD USA. RP Berlin, I (reprint author), CHU Pitie Salpetriere, Serv Pharmacol, 47 Bd Hop, FR-75013 Paris, France. EM ivan.berlin@psl.ap-hop-paris.fr OI Singleton, Edward G./0000-0003-3442-877X; Vorspan, Florence/0000-0001-5168-3727 NR 25 TC 6 Z9 7 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1022-6877 J9 EUR ADDICT RES JI Eur. Addict. Res. PY 2005 VL 11 IS 2 BP 62 EP 68 DI 10.1159/000083034 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 909UZ UT WOS:000227887500002 PM 15785066 ER PT J AU Drenth, JPH Martina, JA te Morsche, RHM Jensen, JBMJ Bonifacino, JS AF Drenth, JPH Martina, JA te Morsche, RHM Jensen, JBMJ Bonifacino, JS TI Molecular characterization of hepatocystin, the protein that is defective in autosomal dominant polycystic liver disease. SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Meeting Abstract C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Med Ctr St Radboud, Dept Med, Div Gastroenterol & Hepatol, Nijmegen, Netherlands. RI Drenth, J.P.H./H-8025-2014; te Morsche, Rene/P-9143-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD JAN PY 2005 VL 17 IS 1 BP A20 EP A20 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 893LF UT WOS:000226719800084 ER PT J AU Drenth, JPH Tahvanainen, E Morsche, RHMT Tahvanainen, P Kaarianen, H Hockerstedt, K van de Kamp, JM Breuning, MH Jansen, JBMJ AF Drenth, JPH Tahvanainen, E Morsche, RHMT Tahvanainen, P Kaarianen, H Hockerstedt, K van de Kamp, JM Breuning, MH Jansen, JBMJ TI Abnormal hepatocystin caused by truncating PRKCSH mutations lead to autosomal dominant polycystic liver disease. SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Meeting Abstract C1 Univ Med Ctr St Radboud, Dept Med, Div Gastroenterol & Hepatol, Nijmegen, Netherlands. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Helsinki, Dept Med Genet, Helsinki, Finland. Natl Publ Hlth Inst, Dept Human Mol Genet, Helsinki, Finland. Univ Turku, Dept Med Genet, SF-20500 Turku, Finland. Univ Turku, Cent Hosp, Dept Pediat, SF-20500 Turku, Finland. Helsinki Univ Hosp, Transplantat & Liver Surg Unit, FIN-00170 Helsinki, Finland. Leiden Univ, Ctr Med, Dept Human & Clin Genet, Leiden, Netherlands. RI Drenth, J.P.H./H-8025-2014; te Morsche, Rene/P-9143-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD JAN PY 2005 VL 17 IS 1 BP A11 EP A12 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 893LF UT WOS:000226719800058 ER PT J AU Zwiers, A Konijn, T Borm, MEA Pena, AS Strober, W Bouma, G AF Zwiers, A Konijn, T Borm, MEA Pena, AS Strober, W Bouma, G TI Polymorphism in the interleukin 12B gene in colitis susceptible mice affects formation of biologically active IL-12 heterodimers. SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Meeting Abstract C1 Vrije Univ Amsterdam, Ctr Med, Immunogenet Lab, Amsterdam, Netherlands. NIH, Mucosal Immun Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD JAN PY 2005 VL 17 IS 1 BP A33 EP A34 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 893LF UT WOS:000226719800123 ER PT J AU Properzi, F Carulli, D Asher, RA Muir, E Camargo, LM van Kuppevelt, TH ten Dam, GB Furukawa, Y Mikami, T Sugahara, K Toida, T Geller, HM Fawcett, JW AF Properzi, F Carulli, D Asher, RA Muir, E Camargo, LM van Kuppevelt, TH ten Dam, GB Furukawa, Y Mikami, T Sugahara, K Toida, T Geller, HM Fawcett, JW TI Chondroitin 6-sulphate synthesis is up-regulated in injured CNS, induced by injury-related cytokines and enhanced in axon-growth inhibitory glia SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE astrocyte; axon regeneration; CNS repair; oligodendrocyte; proteoglycan; sulfotransferase ID SPINAL-CORD-INJURY; ACETYLGALACTOSAMINE 4-SULFATE 6-O-SULFOTRANSFERASE; OLIGODENDROCYTE PRECURSOR CELLS; DERMATAN SULFATE BIOSYNTHESIS; OUTGROWTH-PROMOTING ACTIVITY; CENTRAL-NERVOUS-SYSTEM; ADULT-RAT BRAIN; NEURITE OUTGROWTH; MOLECULAR-CLONING; EXTRACELLULAR-MATRIX AB Chondroitin sulphate proteoglycans (CSPGs) are up-regulated in the CNS after injury and inhibit axon regeneration mainly through their glycosaminoglycan (CS-GAG) chains. We have analysed the mRNA levels of the CS-GAG synthesizing enzymes and measured the CS-GAG disaccharide composition by chromatography and immunocytochemistry. Chondroitin 6-sulfotransferase 1 (C6ST1) is up-regulated in most glial types around cortical injuries, and its sulphated product CS-C is also selectively up-regulated. Treatment with TGFalpha and TGFbeta, which are released after brain injury, promotes the expression of C6ST1 and the synthesis of 6-sulphated CS-GAGs in primary astrocytes. Oligodendrocytes, oligodendrocyte precursors and meningeal cells are all inhibitory to axon regeneration, and all express high levels of CS-GAG, including high levels of 6-sulphated GAG. In axon growth-inhibitory Neu7 astrocytes C6ST1 and 6-sulphated GAGs are expressed at high levels, whereas in permissive A7 astrocytes they are not detectable. These results suggest that the up-regulation of CSPG after CNS injury is associated with a specific sulphation pattern on CS-GAGs, mediating the inhibitory properties of proteoglycans on axonal regeneration. C1 Univ Cambridge, Ctr Brain Repair, Cambridge CB2 2PY, England. Univ Cambridge, Dept Anat, Cambridge, England. Merck Sharp & Dohme Ltd, Neurosci Res Ctr, Harlow CM20 2QR, Essex, England. Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, Dept Biochem, Nijmegen, Netherlands. Chiba Univ, Grad Sch Pharmaceut Sci, Chiba, Japan. Kobe Pharmaceut Univ, Dept Biochem, Kobe, Hyogo, Japan. NHLBI, NIH, Bethesda, MD 20892 USA. RP Fawcett, JW (reprint author), Univ Cambridge, Ctr Brain Repair, Forvie Site, Cambridge CB2 2PY, England. EM jf108@cam.ac.uk RI Kuppevelt, A.H.M.S.M./L-4463-2015; OI Carulli, Daniela/0000-0003-1365-7063; Geller, Herbert/0000-0002-7048-6144; Fawcett, James/0000-0002-7990-4568 NR 73 TC 105 Z9 107 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JAN PY 2005 VL 21 IS 2 BP 378 EP 390 DI 10.1111/j.1460-9568.2005.03876.x PG 13 WC Neurosciences SC Neurosciences & Neurology GA 891IP UT WOS:000226574800007 PM 15673437 ER PT J AU Green, PG Levine, JD AF Green, PG Levine, JD TI Sexual dimorphism in the effect of nonhabituating stress on neurogenic plasma extravasation SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE bradykinin; gender; HPA; inflammation; sound stress; sympathoadrenal stress axis ID BETA-ADRENERGIC-RECEPTORS; NERVOUS-SYSTEM; INFLAMMATORY RESPONSE; VASCULAR-PERMEABILITY; INDUCED MODULATION; GENDER-DIFFERENCES; ENDOTHELIAL-CELLS; IMMUNE FUNCTION; ADRENAL-GLAND; JOINT INJURY AB The sympathoadrenal axis contributes to the sexual dimorphism of the inflammatory response. As stress both activates the sympathoadrenal axis and profoundly affects inflammation and inflammatory disease, we evaluated whether stress exerts a sexually dimorphic effect on a major component of the inflammatory response, plasma extravasation. We evaluated the effect of a nonhabituating stress, repeated intermittent sound (30 min/day for 4 days), on neurogenic synovial plasma extravasation, induced by bradykinin in the rat knee joint. Sound stress profoundly inhibited bradykinin-induced plasma extravasation in male rats, but profoundly enhanced it in female rats. These effects took 24 h to fully develop after the last exposure to stress. In gonadectomized males, bradykinin-induced plasma extravasation was lower than intact males, and sound stress now enhanced it, i.e. gonadectomized males were phenotypically like intact females. In gonadectomized females, bradykinin-induced plasma extravasation was greater than in intact adult females, and sound stress still enhanced it. Adrenal enucleation significantly attenuated the effect of sound stress on bradykinin-induced plasma extravasation in both male and female rats. We tested the hypothesis that these effects of sound stress were due to sustained enhanced plasma levels of stress hormones. Corticosterone and epinephrine, only when administered in combination, over five days, produced a qualitatively similar effect as sound stress, i.e. bradykinin-induced plasma extravasation was significantly decreased in males and increased in females. These findings suggest that a combined effect of the hypothalamic-pituitary adrenal and sympathoadrenal stress axes are responsible for the marked sexual dimorphism in the effect of stress on the inflammatory response. C1 Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, NIH Pain Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Green, PG (reprint author), Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, NIH Pain Ctr, C522 Box 0440,521 Parnassus Ave, San Francisco, CA 94143 USA. EM paul@itsa.ucsf.edu RI Green, Paul/C-5943-2011 NR 69 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JAN PY 2005 VL 21 IS 2 BP 486 EP 492 DI 10.1111/j.1460-9568.2005.03872.x PG 7 WC Neurosciences SC Neurosciences & Neurology GA 891IP UT WOS:000226574800017 PM 15673447 ER PT J AU Gohagan, JK Marcus, PM Fagerstrom, RM Black, WC Kramer, BS Pinsky, PF Prorok, PC AF Gohagan, John K. Marcus, Pamela M. Fagerstrom, Richard M. Black, William C. Kramer, Barnett S. Pinsky, Paul F. Prorok, Philip C. BE Gibson, PG TI Screening for lung cancer SO EVIDENCE-BASED RESPIRATORY MEDICINE LA English DT Article; Book Chapter ID SPIRAL COMPUTED-TOMOGRAPHY; RANDOMIZED FEASIBILITY; ACTION PROJECT; CT; NEUROBLASTOMA; IMPACT; TRIAL C1 [Gohagan, John K.; Pinsky, Paul F.] NCI, Early Detect Res Grp, Bethesda, MD 20892 USA. [Marcus, Pamela M.; Fagerstrom, Richard M.; Prorok, Philip C.] NCI, Biometry Res Grp, Bethesda, MD 20892 USA. [Black, William C.] Dartmouth Hitchcock Med Ctr, Dept Radiol, Lebanon, NH 03766 USA. RP Gohagan, JK (reprint author), NCI, Early Detect Res Grp, Bethesda, MD 20892 USA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-98737-7 PY 2005 BP 81 EP 87 DI 10.1002/9780470987377.ch6 D2 10.1002/9780470987377 PG 7 WC Respiratory System SC Respiratory System GA BXZ83 UT WOS:000297724800006 ER PT J AU Ramat, S Leigh, RJ Zee, DS Optican, LM AF Ramat, S Leigh, RJ Zee, DS Optican, LM TI Ocular oscillations generated by coupling of brainstem excitatory and inhibitory saccadic burst neurons SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE brainstem; burst neurons; postinhibitory rebound discharge; saccadic mechanism; saccadic oscillations ID ALERT SQUIRREL-MONKEY; EYE-MOVEMENTS; SUPERIOR COLLICULUS; HORIZONTAL SACCADES; OMNIPAUSE NEURONS; DISTRIBUTED MODEL; VISUAL FIXATION; LOCAL FEEDBACK; CEREBELLUM; PHYSIOLOGY AB The human saccadic system is potentially unstable and may oscillate if the burst neurons, which generate saccades, are not inhibited by omnipause neurons. A previous study showed that combined saccade vergence movements can evoke oscillations in normal subjects. We set out to determine: 1) whether similar oscillations can be recorded during other paradigms associated with inhibition of omnipause neurons; 2) whether lesions of the fastigial nuclei disrupt such oscillations; and 3) whether such oscillations can be reproduced using a model based on the coupling of excitatory and inhibitory burst neurons. We recorded saccadic oscillations during vergence movements, combined saccade-vergence movements, vertical saccades, pure vergence and blinks in three normal subjects, and in a patient with saccadic hypermetria due to a surgical lesion affecting both fastigial nuclei. During combined saccade-vergence, normal subjects and the cerebellar patient developed small-amplitude (0.1 - 0.5degrees), high-frequency (27 - 35 Hz), conjugate horizontal saccadic oscillations. Oscillations of a similar amplitude and frequency occurred during blinks, pure vergence and vertical saccades. One normal subject could generate saccadic oscillations voluntarily (similar to0.7degrees amplitude, 25 Hz) during sustained convergence. Previous models proposed that high-frequency eye oscillations produced by the saccadic system ( saccadic oscillations), occur because of a delay in a negative feedback loop around high-gain, excitatory burst neurons in the brainstem. The feedback included the cerebellar fastigial nuclei. We propose another model that accounts for saccadic oscillations based on 1) coupling of excitatory and inhibitory burst neurons in the brainstem and 2) the hypothesis that burst neurons show post-inhibitory rebound discharge. When omnipause neurons are inhibited ( as during saccades, saccade-vergence movements and blinks), this new model simulates oscillations with amplitudes and frequencies comparable to those in normal human subjects. The finding of saccadic oscillations in the cerebellar patient is compatible with the new model but not with the recent models including the fastigial nuclei in the classic negative-feedback loop model. Our model proposes a novel mechanism for generating oscillations in the oculomotor system and perhaps in other motor systems too. C1 Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21231 USA. Case Western Reserve Univ, Vet Affairs Med Ctr, Dept Neurol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Univ Hosp, Cleveland, OH 44106 USA. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Ramat, S (reprint author), Johns Hopkins Univ, Dept Neurol, Pathol Bldg,Suite 2-210,600 N Wolfe Str, Baltimore, MD 21231 USA. EM stefano@dizzy.med.jhu.edu RI Ramat, Stefano/E-6495-2011 OI Ramat, Stefano/0000-0001-5932-186X FU NEI NIH HHS [EY01849, EY06717] NR 56 TC 52 Z9 54 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JAN PY 2005 VL 160 IS 1 BP 89 EP 106 DI 10.1007/s00221-004-1989-8 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 875IM UT WOS:000225413700009 PM 15289966 ER PT J AU Hanes, DP Smith, MK Optican, LM Wurtz, RH AF Hanes, DP Smith, MK Optican, LM Wurtz, RH TI Recovery of saccadic dysmetria following localized lesions in monkey superior colliculus SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE superior colliculus; saccade; recovery of function; saccadic dysmetria; saccade latency; saccade velocity; monkey; oculomotor; topographic reorganization ID FRONTAL EYE-FIELD; RESTRICTED DEAFFERENTATION; TARGET SELECTION; BEHAVING MONKEY; CORTICAL AREAS; ADULT MONKEYS; MOVEMENTS; CORTEX; PLASTICITY; NEURONS AB Damage to the monkey superior colliculus (SC) produces deficits in the generation of saccadic eye movements. Recovery of the accuracy of saccades is rapid, but saccadic latency and peak velocity recover slowly or not at all. In the present experiments we revisited the issue of recovery of function following localized lesions of the SC using three methodological advances: implantation of wire recording electrodes into the SC for the duration of the experiment to ensure that we were recording from the same site on the SC map on successive days; quantification of changes in saccadic accuracy, latency, and velocity using a standard grid of target points in the visual field contralateral to the SC lesion; measurement of movement field size to quantitatively determine any changes following the lesion. We confirmed a decrease in saccadic accuracy following electrolytic lesions of the SC, and we found that this dysmetria recovered within about 4 days. Saccadic latency increased for saccades to the lesion area and this deficit persisted. Peak saccadic velocity decreased immediately after the lesion and decreased further during the 10 days to 2 weeks of the experiment. We found no indication of an expansion of the movement fields of neurons adjacent to the lesion area. This lack of reorganization suggests that movement field changes within the SC cannot mediate the recovery in accuracy of the saccade. The persistence of the latency and velocity deficits despite the recovery of amplitude deficits indicates that saccadic latency and peak velocity are dependent upon the SC whereas saccadic amplitude is not. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Wurtz, RH (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM bob@lsr.nei.nih.gov NR 43 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JAN PY 2005 VL 160 IS 3 BP 312 EP 325 DI 10.1007/s00221-004-2013-z PG 14 WC Neurosciences SC Neurosciences & Neurology GA 887JT UT WOS:000226302800005 PM 15448959 ER PT J AU Khanna-Gupta, A Zibello, T Idone, V Sun, H Lekstrom-Himes, J Berliner, N AF Khanna-Gupta, A Zibello, T Idone, V Sun, H Lekstrom-Himes, J Berliner, N TI Human neutrophil collagenase expression is C/EBP-dependent during myeloid development SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID LACTOFERRIN GENE PROMOTER; DISPLACEMENT PROTEIN CDP/CUT; TRANSCRIPTION FACTOR; CELL LINE; C-MYB; EPSILON; DIFFERENTIATION; ALPHA; PU.1; GRANULOCYTE AB Objective. Human neutrophil collagenase (HNC) is one of several secondary granule proteins (SGP) expressed late in the myeloid maturation pathway. SGPs are encoded by unlinked and functionally diverse genes that are hypothesized to be coordinately regulated at the transcriptional level and demonstrate uniform dysregulation in leukemic cells. In support of the hypothesis that tissue and stage-specific expression of SGP genes is regulated by shared factor(s), we sought to identify factors responsible for positive regulation of the SGP genes. Methods. Using 5' deletion analysis, we identified a minimal HNC promoter located within the first 193 bp upstream of the transcription start site. Three CCAAT enhancer binding protein (C/EBP) sites were identified within this region and their functional importance was confirmed by mutational analysis, gel retardation, and oligonucleotide pulldown assays. Using chromatin immunoprecipitation (ChIP), we demonstrated that C/EBPalpha binds to the SGP gene promoters lactoferrin and HNC in nonexpressing cells. Upon induction of maturation, C/EBPalpha binds to these promoters and this binding correlates with the expression of both SGP genes. Conclusion. We conclude that in the later stages of myeloid development, SGP genes are coordinately upregulated, and that members of the C/EBP family of transcription factors, in particular C/EBPalpha and C/EBPepsilon, play specific and unique roles in upregulating their expression. (C) 2005 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Yale Univ, Sch Med, Dept Internal Med, Sect Hematol, New Haven, CT 06510 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Berliner, N (reprint author), Yale Univ, Sch Med, Dept Internal Med, Sect Hematol, 333 Cedar St, New Haven, CT 06510 USA. EM nancy.berliner@yale.edu FU NHLBI NIH HHS [P01-HL63357]; NIDDK NIH HHS [R01-DK53471] NR 41 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JAN PY 2005 VL 33 IS 1 BP 42 EP 52 DI 10.1016/j.exphem.2004.09.009 PG 11 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 894TV UT WOS:000226815400006 PM 15661397 ER PT J AU Czapiga, M Gao, JL Kirk, A Lekstrom-Himes, J AF Czapiga, M Gao, JL Kirk, A Lekstrom-Himes, J TI Human platelets exhibit chemotaxis using functional N-formyl peptide receptors SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID SOLUBLE CD40 LIGAND; MESSENGER-RNA EXPRESSION; HUMAN-NEUTROPHILS; STAPHYLOCOCCUS-AUREUS; CD40-CD40 LIGAND; ACTIVATED PLATELETS; UP-REGULATION; GUINEA-PIGS; IN-VITRO; CELL AB Objective. Activated platelets participate in inflammatory and microbicidal processes by upregulation of surface selectins, shedding of CD40 ligand, and release of platelet microbicidal proteins and microparticles. Given their myeloid lineage, we hypothesized that platelets express functional N-formyl peptide receptors and respond to the bacterially derived chemotactic peptide N-formyl peptide with gradient-driven chemotaxis. Methods and Results. Here we show specific binding of N-formyl peptides to the surface of activated platelets. Platelet expression and function of the formyl peptide receptor, FPR, was verified by RT-PCR of the differentiated megakaryocyte MEG-01 cell line, immunoblotting of platelet proteins, and calcium mobilization in platelets with formyl peptide binding. Furthermore, we demonstrate gradient-driven chemotaxis of platelets by video microscopy and transwell migration toward formyl peptides. We also show that endogenous formyl peptides, released by eukaryotic mitochondria from necrotic cells, induce chemotaxis using formyl peptide receptors expressed by thrombin-activated platelets. Conversely, supernatants from cells undergoing apoptotic cell death do not induce platelet chemotaxis. Platelet chemotaxis to formyl peptides was blocked with FPR-specific antibody as well as by pertussis toxin inhibition of the formyl peptide G-coupled receptor. Conclusion. These data establish a new role for platelets in host defense and suggest reexamination of their active function in microbicidal and other host defense activities. (C) 2005 International Society for Experimental Hematology. Published by Elsevier Inc. C1 NIAID, Host Def Lab, Bethesda, MD 20892 USA. NIDDKD, Transplantat & Autoimmun Branch, Bethesda, MD 20892 USA. USN, Med Res Ctr, Bethesda, MD 20084 USA. RP Lekstrom-Himes, J (reprint author), Millennium Pharmaceut Inc, 35 Landsdowne St, Cambridge, MA 02139 USA. EM lekstrom@mpi.com NR 57 TC 44 Z9 45 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JAN PY 2005 VL 33 IS 1 BP 73 EP 84 DI 10.1016/j.exphem.2004.09.010 PG 12 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 894TV UT WOS:000226815400009 PM 15661400 ER PT J AU De Flora, S Izzotti, A D'Agostini, F Bennicelli, C You, M Lubet, RA Balansky, RM AF De Flora, S Izzotti, A D'Agostini, F Bennicelli, C You, M Lubet, RA Balansky, RM TI Induction and modulation of lung tumors: Genomic and transcriptional alterations in cigarette smoke-exposed mice SO EXPERIMENTAL LUNG RESEARCH LA English DT Article; Proceedings Paper CT 4th International Mouse Lung Tumorigenesis Symposium CY OCT 23-26, 2003 CL Jackson Lab, Bar Harbor, ME HO Jackson Lab DE chemoprevention; cigarette smoke; genomic alterations; lung tumors; murine models; transcriptional alterations ID ENVIRONMENTAL TOBACCO-SMOKE; RESPIRATORY-TRACT; CHEMOPREVENTIVE AGENTS; N-ACETYLCYSTEINE; HAIRLESS MICE; END-POINTS; CARCINOGENICITY; CANCER; MOUSE; A/J AB Cigarette smoke plays a major role in the epidemiology of lung cancer, and smoke components have extensively been investigated in carcinogenicity and chemoprevention studies in experimental animals. However, it is much more difficult to reproduce the tumorigenicity of the whole complex mixture, in preclinical models. The authors review here some results obtained in their laboratories, dealing with the induction of lung tumors, and genomic and transcriptional alterations in smoke-exposed mice. The authors were successful in inducing lung tumors in 4 strains of mice exposed whole-body to environmental cigarette smoke, including Swiss albino, A/J, SKH-1 hairless, and p53 mutant (UL533 x A/J)F-1 mice. However the tumor genic response was rather weak in all strains. Much more intense were the smoke-induced alterations of a variety of intermediate biomarkers, such as cytogenetic end points in pulmonary alveolar macrophages, bone marrow, and peripheral blood erythrocytes; apoptosis, p53 oncoprotein, and proliferating cell nuclear antigen in the bronchial epithelium; bulky DNA adducts, 8-hydroxy-2-deoxyguanosine; multigene expression, and thiobarbituric acid-reactive aldehydes in whole lung and several other organs. Smoke-induced genomic and transcriptional alterations were suitable for evaluating their modulation by chemopreventive agents, as shown in studies using the thiol N-acetylcysteine and the nonsteroidal anti-inflammatory drug sulindac. C1 Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy. Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA. NCI, Div Canc Prevent, Chemoprevent Agent Dev Grp, Bethesda, MD USA. Natl Oncol Ctr, Lab Chem Mutagenesis & Carcinogenesis, Sofia, Bulgaria. RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, Via Pastore 1, I-16132 Genoa, Italy. EM sdf@unige.it OI izzotti, alberto/0000-0002-8588-0347 FU NCI NIH HHS [N01-CN-05122, N01-CN-75008] NR 37 TC 12 Z9 12 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD JAN-FEB PY 2005 VL 31 IS 1 BP 19 EP 35 DI 10.1080/01902140490494986 PG 17 WC Respiratory System SC Respiratory System GA 885DN UT WOS:000226137400003 PM 15765917 ER PT J AU Linnoila, RI Naizhen, X Meuwissen, R Berns, A DeMayo, FJ AF Linnoila, RI Naizhen, X Meuwissen, R Berns, A DeMayo, FJ TI Mouse lung neuroendocrine carcinomas: Distinct morphologies, same transcription factors SO EXPERIMENTAL LUNG RESEARCH LA English DT Article; Proceedings Paper CT 4th International Mouse Lung Tumorigenesis Symposium CY OCT 23-26, 2003 CL Jackson Lab, Bar Harbor, ME HO Jackson Lab DE achaete-scute homolog-1; Clara cell; conditional; lung cancer; mouse; neuroendocrine; p53; premalignant changes; Rb-1; transcription factors; transgenic ID ACHAETE-SCUTE HOMOLOG-1; CLARA CELL; SV40-TRANSFORMED CELLS; CANCER; EXPRESSION; MODEL; DIFFERENTIATION; CLASSIFICATION; ANTIGEN; TUMORS AB Constitutive expression of human achaete-scute homolog-1 (hASH-1) in combination with simian virus large T antigen under the Clara cell 10-kDa secretary protein (CC10) promoter results in adenocarcinomas with focal neuroendocrine (NE) differentiation. Mice carrying conditional alleles for both Rb-1 and p53 in lung epithelial cells develop aggressive lung tumors with similarities to human small cell lung cancers, including high level expression of ASH-1, NE markers, and extrapulmonary metastases. Tumors in both models originate from bronchiolar epithelium, reveal a range of Premalignant changes, express thyroid transcription factor-1 (TTF-1), a marker of peripheral airway cell lineage, and display varying degrees of bidirectional epithelial/NE differentiation. C1 NCI, Cell & Canc Biol Branch, Canc Res Ctr, NIH, Rockville, MD 20850 USA. Netherlands Canc Inst, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands. Netherlands Canc Inst, Ctr Biomed Genet, Amsterdam, Netherlands. Baylor Univ, Sch Med, Dept Mol & Cell Biol, Houston, TX USA. RP Linnoila, RI (reprint author), NCI, Cell & Canc Biol Branch, Canc Res Ctr, NIH, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. EM ill7@nih.gov NR 40 TC 8 Z9 9 U1 1 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD JAN-FEB PY 2005 VL 31 IS 1 BP 37 EP 55 DI 10.1080/01902140490495002 PG 19 WC Respiratory System SC Respiratory System GA 885DN UT WOS:000226137400004 PM 15765918 ER PT J AU Maciag, A Anderson, LM AF Maciag, A Anderson, LM TI Reactive oxygen species and lung tumorigenesis by mutant K-ras: A working hypothesis SO EXPERIMENTAL LUNG RESEARCH LA English DT Article; Proceedings Paper CT 4th International Mouse Lung Tumorigenesis Symposium CY OCT 23-26, 2003 CL Jackson Lab, Bar Harbor, ME HO Jackson Lab DE cyclooxygenase; K-ras mutant; lung tumor; reactive oxygen ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; DIESEL EXHAUST PARTICLES; OXIDATIVE DNA-DAMAGE; INTESTINAL EPITHELIAL-CELLS; MESSENGER-RNA EXPRESSION; PROTEIN-KINASE-C; MOUSE LUNG; HA-RAS; CANCER-RISK; ANTIOXIDANT ENZYMES AB Wild-type K-ras is tumor suppressive in mouse lung, but mutant K-ras is actively oncogenic. Thus, the mutant protein must acquire new, dominant protumorigenic properties. Generation of reactive oxygen species could be one such property. The authors demonstrate increased peroxides in lung epithelial cells (E10)-transfected with mutant hK-ras(va112). An associated increase in DNA damage (comet assay) correlates with increased cyclooxygenase-2 protein. This DNA damage is completely abrogated by a specific cyclooxygenase-2 inhibitor (SC58125) or by a cell-permeable modified catalase. Literature is reviewed regarding generation of reactive oxygen and cyclooxygenase-2 induction by ras, cyclooxygenase-2 release of DNA-damaging reactive oxygen, and involvement Of cyclooxygenase-2 and reactive oxygen in lung cancer. C1 NCI, Comparat Carcinogenesis Lab, Ft Detrick, MD 21702 USA. RP Anderson, LM (reprint author), NCI, Comparat Carcinogenesis Lab, Bldg 538, Ft Detrick, MD 21702 USA. EM Andersol@mail.ncifcrf.gov NR 127 TC 10 Z9 10 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD JAN-FEB PY 2005 VL 31 IS 1 BP 83 EP 104 DI 10.1080/01902140490495048 PG 22 WC Respiratory System SC Respiratory System GA 885DN UT WOS:000226137400006 PM 15765920 ER PT J AU Lubet, R Wang, Y Zhang, ZQ You, M AF Lubet, R Wang, Y Zhang, ZQ You, M TI Mouse models incorporating alterations in the major tumor suppressor genes P53 and p16: Their use in screening for potential carcinogens, developing further relevant mouse models, and screening for potential chemopreventive and chemotherapetutic agents SO EXPERIMENTAL LUNG RESEARCH LA English DT Article; Proceedings Paper CT 4th International Mouse Lung Tumorigenesis Symposium CY OCT 23-26, 2003 CL Jackson Lab, Bar Harbor, ME HO Jackson Lab DE P16; P53; carcinogens; lung cancer; mice ID A/J MICE; CIGARETTE-SMOKE; PULMONARY CARCINOGENESIS; TRANSGENIC MOUSE; TOBACCO-SMOKE; KNOCKOUT MICE; LUNG-TUMORS; CANCER; SUSCEPTIBILITY; COMBINATION AB This review is primarily a follow up to an initial review on this subject that the authors published 4 years ago [Lubet et al., Exp Lung Res. 2000; 581-593]. The present review gives a brief discussion of certain background points and rationale for development of these specific models, which had been presented in greater detail in the earlier article. In that initial article the authors identified the potential use of mutant mice in screening for carcinogens as well as preventive or therapeutic agents, discussed the relevance of the dominant-negative P53 mutation, as contrasted with knockout P53 mice, and briefly discussed the pros and cons of mice with a germline mutation in tumor suppressor genes in developing mouse models. The primary objective of the present review is to describe more recent studies using mice the dominant-negative P53 mutation as well as to introduce studies with mice with a heterozygous knockout of the P16/Ink4A ARF locus. C1 NCI, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. RP Lubet, R (reprint author), NCI, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. EM lubetr@mail.nih.gov NR 30 TC 9 Z9 9 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD JAN-FEB PY 2005 VL 31 IS 1 BP 117 EP 133 DI 10.1080/01902140490495499 PG 17 WC Respiratory System SC Respiratory System GA 885DN UT WOS:000226137400008 PM 15765922 ER PT J AU Allers, KA Bergstrom, DA Ghazi, LJ Kreiss, DS Walters, JR AF Allers, KA Bergstrom, DA Ghazi, LJ Kreiss, DS Walters, JR TI MK801 and amantadine exert different effects on subthalamic neuronal activity in a rodent model of Parkinson's disease SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Parkinson's disease; dyskinesias; basal ganglia; amantadine; dopamine; glutamate; NMDA antagonists; subthalamic nucleus; MK801; oscillations ID METHYL-D-ASPARTATE; DEEP-BRAIN-STIMULATION; DOPAMINE-RECEPTOR STIMULATION; LEVODOPA-INDUCED DYSKINESIAS; ECHO-PLANAR MRI; SUBSTANTIA-NIGRA; GLOBUS-PALLIDUS; BASAL GANGLIA; MULTISECOND OSCILLATIONS; MOTOR FLUCTUATIONS AB Efforts to develop adjuvant therapies for the treatment of Parkinson's disease (PD) have led to interest in drugs that could mimic the therapeutic effects of lesion or deep brain stimulation of the subthalamic nucleus (STN). Extracellular single unit recordings were conducted to determine whether noncompetitive NMDA receptor blockade, suggested to have potential as an adjuvant treatment in PD, attenuates rate increases and firing pattern changes observed in the STN in a rodent model of PD. Systemic administration of the noncompetitive NMDA antagonist MK801 to rats with unilateral dopamine cell lesions did not significantly alter burstiness or interspike interval coefficient of variation, although mean firing rate decreased by a modest 20% with 50% of neurons showing decreases in rate >15% and spike train power in the 3-8-Hz (theta) range was reduced. MK801, combined with the D1 dopamine agonist SKF 38393 in intact rats or administered alone in lesioned rats, also significantly reduced incidence of multisecond (2-60 s) periodic oscillatory activity. Amantadine, a drug currently used as an adjuvant agent in PD whose beneficial effects are commonly attributed to its noncompetitive NMDA antagonist properties, had effects that contrasted with those of MK801. In both intact and lesioned animals, amantadine significantly increased STN firing rates and total spike train power in the 8-50-Hz range and did not alter spike power in the 3-8-Hz range or multisecond oscillatory activity. These observations show that an effective noncompetitive NMDA antagonist such as MK801 induces modest change in STN activity in 6-hydroxydopamine (6-OHDA)-lesioned rats, with the most notable effect on multisecond periodicities in firing rate and theta frequency total spike power. Amantadine's effects differed from MK801's, raising questions about its primary mechanism of action and the role in PD pharmacotherapy of the STN rate increases induced by this drug. Published by Elsevier Inc. C1 NINDS, Neurophysiol Pharmacol Sect, NIH, Porter Neurosci Ctr, Bethesda, MD 20892 USA. RP Allers, KA (reprint author), Univ Oxford, Dept Pharmacol, Mansfield Rd, Oxford OX1 3QT, England. EM Kelly.allers@pharm.ox.ac.uk NR 88 TC 17 Z9 19 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JAN PY 2005 VL 191 IS 1 BP 104 EP 118 DI 10.1016/j.expneurol.2004.08.030 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 886KK UT WOS:000226225900011 PM 15589517 ER PT J AU Driscoll, CT AF Driscoll, CT TI NIH data and resource sharing, data release and intellectual property policies for genomics community resource projects SO EXPERT OPINION ON THERAPEUTIC PATENTS LA English DT Editorial Material DE community resource project; database; data release; data sharing; genomics; HapMap; human genome project (HGP); intellectual property (IP); Human Genome Sequencing Consortium (IHGSC); International Sequencing Consortium (ISC); licensing; Mammalian Gene Collection (MGC); National Human Genome Research Institute (NHGRI); open access; patent; policy; research tool; Trans-NIH Mouse Initiative; The SNP Consortium (TSC); US National Institutes of Health (NIH) ID PATENTS AB The rationale behind the development and adoption of various data release, data and research resource sharing, and patent policies for 'pre-competitive' biological information and critical reagents, notably DNA sequence information, genomic data and research tools generated by National Institutes of Health (NIH) partners and deposited in open access databases and repositories, is described. Specifically covered are the relevant policies implemented by NIH-supported public-private consortia efforts such the International Human Genome Sequencing Consortium (IHGSC), the Trans-NIH Mouse Initiative, the Mammalian Gene Collection (MGC) and the International Haplotype Map Project (HapMap). All of these research initiatives are considered to be community resource projects. In addition, a few key genomics research-related intellectual property (IP) concerns are discussed in conjunction with some proposed possible policy and legal remedies. The hope is that the knowledge gained from the use of the biological resources and the analysis of data generated from these large-scale genomics; projects will be a catalyst for future innovative research including the commercial development of new medicines. C1 NHGRI, Technol Transfer Off, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Driscoll, CT (reprint author), NHGRI, Technol Transfer Off, NIH, US Dept HHS, 12 South Dr MSC 5612, Bethesda, MD 20892 USA. NR 20 TC 0 Z9 0 U1 2 U2 4 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1354-3776 J9 EXPERT OPIN THER PAT JI Expert Opin. Ther. Patents PD JAN PY 2005 VL 15 IS 1 BP 1 EP 8 DI 10.1517/13543776.15.1.1 PG 8 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 892IH UT WOS:000226643300001 ER PT J AU Vadaparampil, ST Ropka, M Stefanek, ME AF Vadaparampil, ST Ropka, M Stefanek, ME TI Measurement of psychological factors associated with genetic testing for hereditary breast, ovarian and colon cancers SO FAMILIAL CANCER LA English DT Article; Proceedings Paper CT 8th International Meeting on Psycho-Social Aspects of Herediatry Cancer CY 2003 CL Barcelona, SPAIN DE anxiety; cancer genetic testing (CGT); depression; distress; psychological factors; psychometrics ID NONPOLYPOSIS COLORECTAL-CANCER; HIGH-RISK BREAST; PSYCHOSOCIAL ISSUES; EVENT SCALE; PSYCHOMETRIC PROPERTIES; FOLLOW-UP; BRCA1; IMPACT; WOMEN; SUSCEPTIBILITY AB Despite numerous individual studies of psychological factors (depression, anxiety, distress) related to genetic testing for inherited cancer syndromes (CGT), there has been no systematic review of the psychological factors are measured among individuals at increased risk for hereditary breast, ovarian, or colon cancer. Our review provides an analysis of psychological factors in studies of CGT and discusses the instruments most commonly used to measure them. We performed a literature search using three major OVID databases from 1993 to January 2003. In the 19 studies that met our inclusion criteria, the most commonly assessed psychological factors were distress, anxiety, and depression. These factors were most often measured by the impact of event scale (IES), the state-trait anxiety inventory (STAI), and the Centers for Epidemiologic Studies and Depression scale (CES-D), respectively., Our results show deficits in the existing body of literature on psychological factors associated with CGT including limited documentation of psychometrics and variability in instrumentation. C1 H Lee Moffit Canc Ctr & Res Inst, Hlth Outcomes & Behav Program, Tampa, FL 33612 USA. Univ Virginia, Sch Med, Dept Hlth Evaluat Sci, Charlottesville, VA 22908 USA. Univ Virginia, Sch Nursing, Charlottesville, VA 22908 USA. Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA. RP Vadaparampil, ST (reprint author), H Lee Moffit Canc Ctr & Res Inst, Hlth Outcomes & Behav Program, 12902 Magnolid Dr,LCS-FOW, Tampa, FL 33612 USA. EM vadapast@moffitt.usf.edu NR 57 TC 25 Z9 25 U1 1 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9600 J9 FAM CANCER JI Fam. Cancer PY 2005 VL 4 IS 2 BP 195 EP 206 DI 10.1007/s10689-004-1446-7 PG 12 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 991GY UT WOS:000233801600020 PM 15951974 ER PT J AU Nieddu, E Melchiori, A Pescarolo, MP Bagnasco, L Biasotti, B Licheri, B Malacarne, D Tortolina, L Castagnino, N Pasa, S Cimoli, G Avignolo, C Ponassi, R Balbi, C Patrone, E D'Arrigo, C Barboro, P Vasile, F Orecchia, P Carnemolla, B Damonte, G Millo, E Palomba, D Fassina, G Mazzei, M Parodi, S AF Nieddu, E Melchiori, A Pescarolo, MP Bagnasco, L Biasotti, B Licheri, B Malacarne, D Tortolina, L Castagnino, N Pasa, S Cimoli, G Avignolo, C Ponassi, R Balbi, C Patrone, E D'Arrigo, C Barboro, P Vasile, F Orecchia, P Carnemolla, B Damonte, G Millo, E Palomba, D Fassina, G Mazzei, M Parodi, S TI Sequence specific peptidomimetic molecules inhibitors of a protein-protein interaction at the helix 1 level of c-Myc SO FASEB JOURNAL LA English DT Article DE D-peptides; protein-protein contacts; growth inhibition; structural studies ID CIRCULAR-DICHROISM; SECONDARY STRUCTURE; CELL-GROWTH; DNA-BINDING; INTERNALIZATION; CONFORMATION; RECOGNITION; NETWORK; COMPLEX; DOMAIN AB Our work is focused in the broad area of strategies and efforts to inhibit protein - protein interactions. The possible strategies in this field are definitely much more varied than in the case of ATP-pocket inhibitors. In our previous work ( 10), we reported that a retro-inverso ( RI) form of Helix1 (H1) of c-Myc, linked to an RI-internalization sequence arising from the third alpha-helix of Antennapedia (Int) was endowed with an antiproliferative and proapoptotic activity toward the cancer cell lines MCF-7 and HCT-116. The activity apparently was dependent upon the presence of the Myc motif. In this work, by ala-scan mapping of the H1 portion of our molecules with Daa, we found two amino acids necessary for antiproliferative activity: D-Lys in 4 and D-Arg in 5 ( numbers refer to L-forms). In the natural hetero-dimer, these two side chains project to the outside of the four alpha-helix bundle. Moreover, we were able to obtain three peptides more active than the original lead. They strongly reduced cell proliferation and survival (RI-Int-VV-H1-E2A, S6A, F8A; RI-Int-VV-H1-S6A, F8A, R11A; RI-Int-VV-H1-S6A, F8A, Q13A): after 8 days at 10 muM total cell number was similar to 1% of the number of cells initially seeded. In these more potent molecules, the ablated side chains project to the inside in the corresponding natural four alpha-helix bundle. In the present work, we also investigated the behavior of our molecules at the biochemical level. Using both a circular dichroism (CD) and a fluorescence anisotropy approach, we noted that side chains projecting at the interior of the four alpha-helix bundle are needed for inducing the partial unfolding of Myc-H2, without an opening of the leucine zipper. Side chains projecting at the outside are not required for this biochemical effect. However, antiproliferative activity had the opposite requirements: side chains projecting at the outside of the bundle were essential, and, on the contrary, ablation of one side chain at a time projecting at the inside increased rather than decreased biological activity. We conclude that our active molecules probably interfere at the level of a protein - protein interaction between Myc-Max and a third protein of the transcription complex. Finally, CD and nuclear magnetic resonance (NMR) data, plus dynamic simulations, suggest a prevalent random coil conformation of the H1 portion of our molecules, at least in diluted solutions. The introduction of a kink ( substitution with proline in positions 5 or 7) led to an important reduction of biological activity. We have also synthesized a longer peptido-mimetic molecule (RI-Int-H1-S6A, F8A-loop-H2) with the intent of obtaining a wider zone of interaction and a stronger interference at the level of the higher-order structure (enhanceosome). RI-Int-H1-S6A, F8A-loop-H2 was less active rather than more active in respect to RI-Int-VV-H1-S6A, F8A, apparently because it has a clear bent to form a - sheet ( CD and NMR data). C1 Univ Genoa, Dept Pharmaceut Sci, I-16132 Genoa, Italy. Natl Canc Inst, Expt Oncol Lab, Genoa, Italy. Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy. Inst Study Macromol, Genoa Sect, Genoa, Italy. Univ Genoa, Dept Biophys Sci & Technol, Genoa, Italy. Natl Canc Inst, Cell Biol Lab, Genoa, Italy. Inst Giannina Gaslini, Genoa, Italy. Ctr Excellence Biomed Res, Dept Expt Med, Biochem Sect, Genoa, Italy. Xeptagen SpA, Naples, Italy. RP Nieddu, E (reprint author), Univ Genoa, Dept Pharmaceut Sci, I-16132 Genoa, Italy. EM erika.nieddu@unige.it OI D'Arrigo, Cristina/0000-0002-5352-5287; VASILE, FRANCESCA/0000-0002-3926-8261; orecchia, paola/0000-0003-0556-9784 NR 24 TC 16 Z9 18 U1 0 U2 5 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 2005 VL 19 IS 1 BP 632 EP + DI 10.1096/fj.04-2369fje PG 26 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 891JH UT WOS:000226576600006 PM 15671156 ER PT J AU Snasel, J Krejcik, Z Jencova, V Rosenberg, I Ruml, T Alexandratos, J Gustchina, A Pichova, I AF Snasel, J Krejcik, Z Jencova, V Rosenberg, I Ruml, T Alexandratos, J Gustchina, A Pichova, I TI Integrase of Mason-Pfizer monkey virus SO FEBS JOURNAL LA English DT Article DE integrase; Mason-Pfizer monkey virus; HIV-1; specificity; structure ID HUMAN-IMMUNODEFICIENCY-VIRUS; PHOTO-CROSS-LINKING; VIRAL-DNA BINDING; HIV-1 INTEGRASE; CATALYTIC DOMAIN; ACTIVE-SITE; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; DIVALENT-CATIONS; TYPE-1 INTEGRASE AB The gene encoding an integrase of Mason-Pfizer monkey virus (M-PMV) is located at the 3'-end of the pol open reading frame. The M-PMV integrase has not been previously isolated and characterized. We have now cloned, expressed, isolated, and characterized M-PMV integrase and compared its activities and primary structure with those of HIV-1 and other retroviral integrases. M-PMV integrase prefers untranslated 3'-region-derived long-terminal repeat sequences in both the 3'-processing and the strand transfer activity assays. While the 3'-processing reaction catalyzed by M-PMV integrase was significantly increased in the presence of Mn2+ and Co2+ and was readily detectable in the presence of Mg2+ and Ni2+ cations, the strand transfer activity was strictly dependent only on Mn2+. M-PMV integrase displays more relaxed substrate specificity than HIV-1 integrase, catalyzing the cleavage and the strand transfer of M-PMV and HIV-1 long-terminal repeat-derived substrates with similar efficiency. The structure-based sequence alignment of M-PMV, HIV-1, SIV, and ASV integrases predicted critical amino acids and motifs of M-PMV integrase for metal binding, interaction with nucleic acids, dimerization, protein structure maintenance and function, as well as for binding of human immunodeficiency virus type 1 and Rous avian sarcoma virus integrase inhibitors 5-CI-TEP, DHPTPB and Y-3. C1 Acad Sci Czech Republ, Inst Organ Chem & Biochem, CR-16610 Prague 6, Czech Republic. Acad Sci Czech Republ, Inst Mol Genet, CR-16610 Prague, Czech Republic. Acad Sci Czech Republ, Ctr Integrated Gen, CR-16610 Prague 6, Czech Republic. NCI, Macromol Crystallog Lab, Frederick, MD 21701 USA. RP Pichova, I (reprint author), Acad Sci Czech Republ, Inst Organ Chem & Biochem, Flemingovo Nam 2, CR-16610 Prague 6, Czech Republic. EM iva.pichova@uochb.cas.cz RI Krejcik, Zdenek/A-3505-2013; Rosenberg, Ivan/G-5602-2014; Pichova, Iva/G-7917-2014 NR 55 TC 13 Z9 14 U1 3 U2 5 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JAN PY 2005 VL 272 IS 1 BP 203 EP 216 DI 10.1111/j.1432-1033.2004.04386.x PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 902LG UT WOS:000227358000018 PM 15634344 ER PT J AU Tozser, J Tropea, JE Cherry, S Bagossi, P Copeland, TD Wlodawer, A Waugh, DS AF Tozser, J Tropea, JE Cherry, S Bagossi, P Copeland, TD Wlodawer, A Waugh, DS TI Comparison of the substrate specificity of two potyvirus proteases SO FEBS JOURNAL LA English DT Article DE nuclear inclusion protease; potyvirus protease; substrate specificity; tobacco etch virus protease; tobacco vein mottling virus protease ID ETCH VIRUS PROTEASE; POLYPROTEIN CLEAVAGE SITE; VPG-PROTEINASE NIA; ENCODED PROTEINASES; IN-VIVO; EXPRESSION AB The substrate specificity of the nuclear inclusion protein a (NIa) proteolytic enzymes from two potyviruses, the tobacco etch virus (TEV) and tobacco vein mottling virus (TVMV), was compared using oligopeptide substrates. Mutations were introduced into TEV protease in an effort to identify key determinants of substrate specificity. The specificity of the mutant enzymes was assessed by using peptides with complementary substitutions. The crystal structure of TEV protease and a homology model of TVMV protease were used to interpret the kinetic data. A comparison of the two structures and the experimental data suggested that the differences in the specificity of the two enzymes may be mainly due to the variation in their S4 and S3 binding subsites. Two key residues predicted to be important for these differences were replaced in TEV protease with the corresponding residues of TVMV protease. Kinetic analyses of the mutants confirmed that these residues play a role in the specificity of the two enzymes. Additional residues in the substrate-binding subsites of TEV protease were also mutated in an effort to alter the specificity of the enzyme. C1 Univ Debrecen, Dept Biochem & Mol Biol, Res Ctr Mol Med, H-4012 Debrecen, Hungary. NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD USA. NCI, Lab Prot Dynam & Signaling, Canc Res Ctr, Frederick, MD USA. RP Tozser, J (reprint author), Univ Debrecen, Dept Biochem & Mol Biol, Res Ctr Mol Med, H-4012 Debrecen, Hungary. EM tozser@indi.biochem.dote.hu; waughd@ncifcrf.gov RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 NR 22 TC 22 Z9 24 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1742-464X EI 1742-4658 J9 FEBS J JI FEBS J. PD JAN PY 2005 VL 272 IS 2 BP 514 EP 523 DI 10.1111/j.1742-4658.2004.04493.x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 902LS UT WOS:000227359200020 PM 15654889 ER PT J AU Potlog-Nahari, C Catherino, WH McKeeby, JL Wesley, R Segars, JH AF Potlog-Nahari, C Catherino, WH McKeeby, JL Wesley, R Segars, JH TI A suboptimal endometrial pattern is associated with a reduced likelihood of pregnancy after a day 5 embryo transfer SO FERTILITY AND STERILITY LA English DT Editorial Material ID IN-VITRO FERTILIZATION; GONADOTROPIN-RELEASING-HORMONE; ASSISTED REPRODUCTION; INVITRO FERTILIZATION; OVARIAN STIMULATION; THICKNESS; IMPLANTATION; ULTRASONOGRAPHY; PROGRAM; PREDICTORS AB This retrospective study examined the association of endometrial pattern and pregnancy after a day 5 ET. The pregnancy rate of women with a triple-line ultrasound endometrial pattern on the day of hCG administration was significantly higher than the pregnancy rate of women with the other ultrasound patterns. This observation suggests that, in a subset of patients, a suboptimal endometrial lining may interfere with assisted reproductive technology success. (Fertil Steril(R) 2005;83:235-7. (C)2005 by American Society for Reproductive Medicine.). C1 Walter Reed Army Med Ctr, Washington, DC 20307 USA. NIH, Bethesda, MD 20892 USA. RP Segars, JH (reprint author), NICHD, Bldg 10,Room 9D-42, Bethesda, MD 20892 USA. EM segarsj@mail.nih.gov NR 16 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2005 VL 83 IS 1 BP 235 EP 237 DI 10.1016/j.fertnstert.2004.05.102 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 889LT UT WOS:000226445200040 PM 15652920 ER PT J AU Rhodes, MC Hebert, CD Herbert, RA Morinello, EJ Roycroft, JH Travlos, GS Abdo, KM AF Rhodes, MC Hebert, CD Herbert, RA Morinello, EJ Roycroft, JH Travlos, GS Abdo, KM TI Absence of toxic effects in F344/N rats and B6C3F(1) mice following subchronic administration of chromium picolinate monohydrate SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE chromium; feed; mice; NTP; picolinate; rats; subchronic; supplement; toxicity ID ZERO DOSE CONTROL; NUTRITIONAL SUPPLEMENT; ABSORPTION; CHLORIDE; INVITRO; WEIGHT; CELLS AB Chromium picolinate monohydrate (CPM) is a synthetic compound heavily marketed to consumers in the United States for use as a dietary supplement for muscle building and weight loss. The National Toxicology Program (NTP) tested the toxicity of this compound based on the potential for widespread consumer exposure and lack of information about its toxicity. Groups of 10 male and 10 female F344/N rats and B6C3F(1) mice were exposed to 0, 80, 240, 2000, 10,000, or 50,000 ppm CPM in feed for 13 weeks. CPM administration produced no effect on body weight gain or survival of rats or mice. Organ weights and organ/body weight ratios in exposed animals were generally unaffected by CPM No compound-related changes in hematology and clinical chemistry parameters were observed. There were no histopathological lesions attributed to CPM in rats or mice. (C) 2004 Elsevier Ltd. All rights reserved. C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. So Res Inst, Birmingham, AL 35255 USA. RP Rhodes, MC (reprint author), Natl Inst Environm Hlth Sci, Mail Drop EC-34,79 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM rhodes2@niehs.nih.gov NR 38 TC 25 Z9 30 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JAN PY 2005 VL 43 IS 1 BP 21 EP 29 DI 10.1016/j.fct.2004.08.006 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 889ME UT WOS:000226446300002 PM 15582192 ER PT J AU Bilski, P Karriker, B DeRose, EF Chignell, CF AF Bilski, P Karriker, B DeRose, EF Chignell, CF TI Hydroethidine is efficiently oxidized by singlet oxygen SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Struct Biol, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S107 EP S107 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700310 ER PT J AU Bonini, MG Siraki, AG Atanassov, BS Mason, RP AF Bonini, MG Siraki, AG Atanassov, BS Mason, RP TI Catalase inactivation by hypochlorite correlates with protein radical formation, aggregation and heme modification. SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S18 EP S18 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700037 ER PT J AU Browne, R Schisterman, E Wactawski-Wende, J Trevisan, M AF Browne, R Schisterman, E Wactawski-Wende, J Trevisan, M TI The "biocycle" study: Analytical and biological variation of biomarkers of oxidative stress during the menstrual cycle SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 SUNY Buffalo, Buffalo, NY 14260 USA. NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S150 EP S150 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700428 ER PT J AU Donzelli, S Espey, MG Thomas, DD Mancardi, D Ridnour, LA Paolocci, N Miranda, KM Lazzarino, G Wink, DA AF Donzelli, S Espey, MG Thomas, DD Mancardi, D Ridnour, LA Paolocci, N Miranda, KM Lazzarino, G Wink, DA TI Nitroxyl formation from hydroxylamine by myoglobin and hydrogen peroxide SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Univ Arizona, Tucson, AZ 85721 USA. Univ Catania, I-95124 Catania, Italy. RI Miranda, Katrina/B-7823-2009 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S99 EP S99 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700285 ER PT J AU Grimes, K Cook, J Mitchell, J AF Grimes, K Cook, J Mitchell, J TI Nitroxides inhibit the TNF-alpha initiated NF-kappa B cytoplasmic to nuclear translocation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S165 EP S165 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700470 ER PT J AU Huang, J Basu, S Huang, Z Hill, J Shields, H Azarov, L Huang, KT Hogg, N King, SB Gladwin, AT Kim-Shapiro, DB AF Huang, J Basu, S Huang, Z Hill, J Shields, H Azarov, L Huang, KT Hogg, N King, SB Gladwin, AT Kim-Shapiro, DB TI Nitrosothiol formation in the reaction of nitrite and hemoglobin SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 Wake Forest Univ, Winston Salem, NC 27109 USA. NIH, Bethesda, MD 20892 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S100 EP S100 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700290 ER PT J AU Hyodo, F Matsumoto, K Matsumoto, A Subramanian, S Mitchell, J Murali, C AF Hyodo, F Matsumoto, K Matsumoto, A Subramanian, S Mitchell, J Murali, C TI Imaging tissue redox staus using MRI and redox sensitive paramagnetic contrast agents: Applications for tumor imaging SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S111 EP S111 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700319 ER PT J AU Ikeno, Y Perez, V Lew, C Cortez, L Chaudhuri, A Qi, WB Levine, RL Yodoi, J Richardson, A AF Ikeno, Y Perez, V Lew, C Cortez, L Chaudhuri, A Qi, WB Levine, RL Yodoi, J Richardson, A TI Overexpression of thioredoxin 1 increases resistance to oxidative stress and alters aging SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NHLBI, NIH, Bethesda, MD 20892 USA. Kyoto Univ, Kyoto, Japan. RI Levine, Rodney/D-9885-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S128 EP S128 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700368 ER PT J AU Kato, G Hunter, C Hunter, L Machado, R Dejam, N Mack, K Lin, E Tremonti, C Sachdev, V Cannon, R Gladwin, M AF Kato, G Hunter, C Hunter, L Machado, R Dejam, N Mack, K Lin, E Tremonti, C Sachdev, V Cannon, R Gladwin, M TI Atorvastatin therapy restores nitric oxide-dependent vascular responsiveness in patients with sickle cell disease SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NHLBI, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NIH, NIDDK, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S153 EP S153 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700439 ER PT J AU Lin, E Machado, R Hunter, L Harris, A Ringwood, L McGowan, V Martyr, S Smith, K Grant, L Schenke, B Gladwin, M AF Lin, E Machado, R Hunter, L Harris, A Ringwood, L McGowan, V Martyr, S Smith, K Grant, L Schenke, B Gladwin, M TI Nitrite consumed during exercise: Arterial-venous nitrite gradients increase with aerobic to anaerobic respiration SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S89 EP S89 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700255 ER PT J AU Mack, AK Machado, RF McGowan, V Sachdev, V Gladwin, MT Kato, GJ AF Mack, AK Machado, RF McGowan, V Sachdev, V Gladwin, MT Kato, GJ TI Sodium nitrite increases regional blood flow in patients with sickle cell disease SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NIH, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S89 EP S89 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700256 ER PT J AU Matsumoto, A Matsumoto, K Sowers, A Koscielniak, J Hyodo, F Devasahayam, N Subramanian, S Mitchell, J Krishna, M AF Matsumoto, A Matsumoto, K Sowers, A Koscielniak, J Hyodo, F Devasahayam, N Subramanian, S Mitchell, J Krishna, M TI Noninvasive EPR assessment of tissue oxygenation using water soluble paramagnetic probes SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S112 EP S112 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700322 ER PT J AU Matsumoto, K Okajo, A Kobayashi, T Mitchell, J Krishna, M Endo, K AF Matsumoto, K Okajo, A Kobayashi, T Mitchell, J Krishna, M Endo, K TI Reduction of a nitroxyl radical by beta-ray irradiation in rat liver SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S118 EP S118 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700336 ER PT J AU Matsumoto, K Hyodo, F Matsumoto, A Subramanian, S Murugesan, R Sowers, A Cook, J Mitchell, J Krishna, M AF Matsumoto, K Hyodo, F Matsumoto, A Subramanian, S Murugesan, R Sowers, A Cook, J Mitchell, J Krishna, M TI Estimation of redox status of a tumor tissue in mice using paramagnetic nitroxyl contrast agent SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S113 EP S113 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700325 ER PT J AU Matsumoto, K Krishna, M Mitchell, J AF Matsumoto, K Krishna, M Mitchell, J TI Novel pharmacokinetic measurement using electron paramagnetic resonance spectroscopy and simulation of in vivo decay of various nitroxyl radicals in mouse blood SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S112 EP S112 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700324 ER PT J AU Okajo, A Endo, K Mitchell, J Krishna, M Matsumoto, K AF Okajo, A Endo, K Mitchell, J Krishna, M Matsumoto, K TI Competition of nitroxyl contrast agents for in vivo tissue redox estimation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S112 EP S112 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700323 ER PT J AU Ramirez, D Mejiba, SG Mason, R AF Ramirez, D Mejiba, SG Mason, R TI Copper catalyzed protein oxidation and its modulation by carbon dioxide: Enhancement of protein radicals in functioning cells SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S129 EP S129 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700371 ER PT J AU Reszka, KJ Bilski, P Denning, GM Chignell, CF Britigan, BE AF Reszka, KJ Bilski, P Denning, GM Chignell, CF Britigan, BE TI Photosensitized oxidation of pyocyanin SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 VAMC, Res Serv, Cincinnati, OH USA. Natl Inst Environ Hlth Sci, NIH, Res Triangle Pk, NC USA. Univ Iowa, Dept Emergency Med, Iowa City, IA USA. Univ Cincinnati, Dept Internal Med, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S107 EP S107 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700311 ER PT J AU Shiva, S Sack, M Huang, Z Ringwood, L Lefer, D Gladwin, M AF Shiva, S Sack, M Huang, Z Ringwood, L Lefer, D Gladwin, M TI Nitrite regulates mitochondrial respiration and limits reperfusion injury SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NHLBI, Vasc Therapeut Sect, CV Branch, NIH, Bethesda, MD 20892 USA. Louisiana State Univ, Hlth Sci Ctr, Shreveport, LA 71105 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S140 EP S141 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700404 ER PT J AU Stadler, K Jenei, V Jakus, J AF Stadler, K Jenei, V Jakus, J TI Beneficial effects of aminoguanidine on the cardiovascular system of diabetic rats SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NIEHS, LPC, NIH, Res Triangle Pk, NC USA. Hungarian Acad Sci, Chem Res Ctr, Budapest, Hungary. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S93 EP S93 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700270 ER PT J AU Swindle, EJ Coleman, JW Metcalfe, DD AF Swindle, EJ Coleman, JW Metcalfe, DD TI Production of reactive oxygen species in both human and mouse mast cells is lipoxygenase-dependent and plays a facilitatory role in antigen mediated cytokine secretion SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NIAID, MCBS, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S54 EP S55 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700147 ER PT J AU Wang, X Bryan, N Macarthur, P Shiva, S Rodriguez, J Gladwin, M Feelisch, M AF Wang, X Bryan, N Macarthur, P Shiva, S Rodriguez, J Gladwin, M Feelisch, M TI Methodologies for detection of basal S-nitrosothiol levels in the circulation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 NHLBI, Vasc Therapeut Sect, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S94 EP S95 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700274 ER PT J AU Whitsett, J Martasek, P Zhao, HT Kalyanaraman, B Vasquez-Vivar, J AF Whitsett, J Martasek, P Zhao, HT Kalyanaraman, B Vasquez-Vivar, J TI Superoxide generation, enos-serine 1179 and enos dimer/monomer ratio in endothelial cells SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 Med Coll Wisconsin, Milwaukee, WI 53226 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S28 EP S28 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700066 ER PT J AU Yuditskaya, S Hoehn, G Suffredini, A Xu, XL Munson, P Gladwin, M Kato, G AF Yuditskaya, S Hoehn, G Suffredini, A Xu, XL Munson, P Gladwin, M Kato, G TI Proteomic identification of dysregulated apolipoprotein expression in pulmonary hypertension secondary to sickle cell disease SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Annual Meeting Society-for-Free-Radical-Biology-and-Medicine CY NOV 16-20, 2005 CL Austin, TX SP Soc Free Rad Biol & Med C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2005 VL 39 SU 1 BP S153 EP S153 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 985VL UT WOS:000233406700438 ER PT J AU Qian, SY Kadiiska, MB Guo, QO Mason, RP AF Qian, SY Kadiiska, MB Guo, QO Mason, RP TI A novel protocal to identify and quantify all spin trapped free radicals from in vitro/in vivo interaction of HO and DMDO: LC/ESR, LC/MS, and dual spin trapping combinations SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE d0/d9-POBN dual spin trapping; LC/ESR; LC/MS; redox forms of spin adduct; Fenton reaction; free radicals ID POLYUNSATURATED FATTY-ACIDS; CARBON-CENTERED RADICALS; IN-VIVO; SOYBEAN LIPOXYGENASE; HYDROXYL RADICALS; HYDROGEN-PEROXIDE; TANDEM MS; RAT BILE; IDENTIFICATION; METABOLISM AB When dimethyl sulfoxide (DMSO) is oxidized via hydroxyl radical (HO*), it forms methyl radicals (*CH3) that can be spin trapped and detected by electron spin resonance (ESR). This ESR spin trapping technique has been widely used in many biological systems to indicate in vivo HO* formation. However, we recently reported that *CH3 might not be the only carbon-centered radical that was trapped and detected by EsR from in vivo DMSO oxidation. In the present study, newly developed combination techniques consisting of dual spin trapping (free radicals trapped by both regular and deuterated alpha-[4-pyridyl]-N-tert-butyl nitrone, d(0)/d(9)-POBN) followed by LC/ESR and LC/MS were used to characterize and quantify all POBN-trapped free radicals from the interaction of HO* and DMSO. In addition to identifying the two well-known free radicals, 'CH3 and *OCH3,, from this interaction, we also characterized two additional free radicals, *CH2OH and *CH2S(O)CH3. Unlike ESR, which can measure POBN adducts only in their radical forms, LGMS identified and quantified all three redox forms, including the ESR-active radical adduct and two ESR-silent forms, the nitrone adduct (oxidized adduct) and the hydroxylamine (reduced adduct). In the bile of rats treated with DMSO and POBN, the ESR-active form of POBN/*CH3 was not detected. However, with the addition of the LC/MS technique, we found similar to0.75 muM POBN/*CH3 hydroxylamme, which represents a great improvement in radical detection sensitivity and reliability. This novel protocol provides a comprehensive way to characterize and quantify in vitro and in vivo free radical formation and will have many applications in biological research. (C) 2004 Elsevier Inc. All rights reserved. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Qian, SY (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM qian1@niehs.nih.gov NR 36 TC 46 Z9 49 U1 1 U2 11 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 2005 VL 38 IS 1 BP 125 EP 135 DI 10.1016/j.freeradbiomed.2004.09.024 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 885QV UT WOS:000226172900016 ER PT J AU Vitkovic, L Maeda, S Aloyo, VJ AF Vitkovic, L Maeda, S Aloyo, VJ TI Characterization of membrane-associated substrates of Ca2+-dependent kinases in astrocytes SO FRONTIERS IN BIOSCIENCE LA English DT Article DE astrocytes; phosphoproteins; membranes; Ca2+-dependent kinases; 2-dimensional electrophoresis ID DEPENDENT PROTEIN-KINASE; RAT-BRAIN; PLASMA-MEMBRANE; PHOSPHORYLATION; EXPRESSION; GAP-43; NEURONS AB Membrane-associated kinase substrates are likely transducers of extracellular signals elicited by neuroimmunomodulators and other signaling molecules. Whereas specific signal transduction pathways in astrocytes are being defined, the global view is lacking. We, therefore, characterized membrane-associated substrates of Ca2+-dependent kinases in primary astrocytes using 2-dimensional gel electrophoresis. Ten proteins were phosphorylated in vitro and characterized with respect to their relative molecular mass ( in the range 10 kDa - 100 kDa), isoelectric point ( range 4.2 - 9.0) and four conditions of phosphorylation. They varied broadly in their requirements for phosphorylation displaying distinct kinase preferences. Eight phosphoproteins were substrates of protease kinase C. Judging by abundance and intensity of phosphorylation, the principal PKC substrates were three acidic proteins associated with the plasma membrane. These results suggest that a relatively small number of membrane-associated proteins serve as transducers of signals mediated by Ca2+-dependent kinases and most of them are PKC substrates in astrocytes. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIMH, Integrat Neural Immune Program, NIH, Bethesda, MD 20892 USA. Med Coll Penn & Hahnemann Univ, Dept Pharmacol, Philadelphia, PA 19129 USA. RP Vitkovic, L (reprint author), 7809 Moorland Lane, Bethesda, MD 20814 USA. EM vitkovic@hotmail.com NR 24 TC 0 Z9 0 U1 0 U2 0 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2005 VL 10 BP 83 EP 87 DI 10.2741/1509 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 970OK UT WOS:000232319300010 PM 15574350 ER PT J AU Vitkovic, L Aloyo, VJ Maeda, S Benzil, DL Bressler, JP Hilt, DC AF Vitkovic, L Aloyo, VJ Maeda, S Benzil, DL Bressler, JP Hilt, DC TI Identification of myristoylated alanine-rich C kinase substrate (MARCKS) in astrocytes SO FRONTIERS IN BIOSCIENCE LA English DT Article DE nervous system; CNS; glia; glial cell; astrocytes; GAP-43; phosphoproteins; plasma membrane; MARCKS; review ID MAJOR SPECIFIC SUBSTRATE; PROTEIN-KINASE; RAT-BRAIN; PHORBOL ESTER; PHOSPHORYLATION; CALCIUM; LOCALIZATION; FIBROBLASTS; EXPRESSION; TRANSLOCATION AB We have characterized membrane-associated substrates of Ca2+-dependent kinases in primary rat astrocytes by in vitro phosphorylation, 2-dimensional gel electrophoresis and autoradiography. The most prominent among these were three acidic, protein kinase C (PKC) substrates. These are important because they likely transduce cytokine and other neuro-immune modulatory signals mediated by PKC. We now show that one of these phosphoproteins is myristoylated alanine-rich PKC kinase substrate ( MARCKS) or phosphomyristin C. The identity was corroborated by one- and 2- dimensional immunoblotting with an MARCKS-specific polyclonal antibody. Exposing primary astrocytes to phorbol 12-myristate 13-acetate stimulated phosphorylation of this protein. The level of MARCKS appeared inversely proportional to the proliferative potential of astrocytes because it was lower in spontaneously transformed as compared to passaged or confluent cells. These data are consistent with previous reports and indicate that one of three major acidic membrane-associated PKC substrates in astrocytes is MARCKS. Thus, MARCKS is likely near-proximal transducer of PKC-mediated signals in astrocytes. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Med Coll Penn & Hahnemann Univ, Dept Pharmacol, Philadelphia, PA 19129 USA. NIMH, Integrat Neural Immune Program, NIH, Bethesda, MD 20892 USA. Kennedy Inst, Dept Neurol, Baltimore, MD 21205 USA. Univ Maryland, Sch Med, Baltimore Vet Hosp, Dept Neurol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Baltimore Vet Hosp, Dept Biochem, Baltimore, MD 21201 USA. New York Med Coll, Dept Neurosurg, Valhalla, NY 10595 USA. Guilford Pharmaceut Inc, Clin Res, Baltimore, MD 21224 USA. RP Vitkovic, L (reprint author), 7809 Moorland Lane, Bethesda, MD 20814 USA. EM vitkovic@hotmail.com NR 37 TC 4 Z9 4 U1 0 U2 0 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2005 VL 10 BP 160 EP 165 DI 10.2741/1517 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 970OK UT WOS:000232319300018 PM 15574358 ER PT J AU Hauser, KF Aldrich, JV Anderson, KJ Bakalkin, G Christie, MJ Hall, ED Knapp, PE Scheff, SW Singh, IN Vissel, B Woods, AS Yakovleva, T Shippenberg, TS AF Hauser, KF Aldrich, JV Anderson, KJ Bakalkin, G Christie, MJ Hall, ED Knapp, PE Scheff, SW Singh, IN Vissel, B Woods, AS Yakovleva, T Shippenberg, TS TI Pathobiology of dynorphins in trauma and disease SO FRONTIERS IN BIOSCIENCE LA English DT Review DE opioids; neuropeptides; neuropeptides processing; drug abuse; spinal cord injury; neurotrauma; pain; glutamate; N-methyl-D-aspartate; AMPA; apoptosis; neurotoxicity; excitotoxicity; striatum; -opioid receptors; review ID KAPPA-OPIOID RECEPTOR; SPINAL-CORD-INJURY; METHYL-D-ASPARTATE; EXCITATORY AMINO-ACIDS; GUINEA-PIG HIPPOCAMPUS; GROWTH-FACTOR RECEPTOR; PROTEIN-KINASE-C; TRANSIENT CEREBRAL-ISCHEMIA; EXPERIMENTAL BRAIN-INJURY; MESSENGER-RNA EXPRESSION AB Dynorphins, endogenous opioid neuropeptides derived from the prodynorphin gene, are involved in a variety of normative physiologic functions including antinociception and neuroendocrine signaling, and may be protective to neurons and oligodendroglia via their opioid receptor-mediated effects. However, under experimental or pathophysiological conditions in which dynorphin levels are substantially elevated, these peptides are excitotoxic largely through actions at glutamate receptors. Because the excitotoxic actions of dynorphins require supraphysiological concentrations or prolonged tissue exposure, there has likely been little evolutionary pressure to ameliorate the maladaptive, non-opioid receptor mediated consequences of dynorphins. Thus, dynorphins can have protective and/or proapoptotic actions in neurons and glia, and the net effect may depend upon the distribution of receptors in a particular region and the amount of dynorphin released. Increased prodynorphin gene expression is observed in several disease states and disruptions in dynorphin processing can accompany pathophysiological situations. Aberrant processing may contribute to the net negative effects of dysregulated dynorphin production by tilting the balance towards dynorphin derivatives that are toxic to neurons and/or oligodendroglia. Evidence outlined in this review suggests that a variety of CNS pathologies alter dynorphin biogenesis. Such alterations are likely maladaptive and contribute to secondary injury and the pathogenesis of disease. C1 Univ Kentucky, Coll Med, Dept Anat & Neurobiol, Lexington, KY 40536 USA. Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA. Univ Florida, Dept Physiol Sci, Gainesville, FL 32610 USA. Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, S-17176 Stockholm, Sweden. Univ Sydney, Dept Pharmacol, No Clin Sch, Pain Management Res Inst, Sydney, NSW 2006, Australia. Univ Kentucky, Coll Med, Spinal Cord & Head Injury Res Ctr, Lexington, KY 40536 USA. Univ Kentucky, Coll Med, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. St Vincents Hosp, Garvan Inst Med Res, Neurobiol Res Program, Darlinghurst, NSW 2010, Australia. NIDA, Integrat Neurosci Sect, IRP, NIH, Baltimore, MD 21224 USA. RP Hauser, KF (reprint author), Univ Kentucky, Coll Med, Dept Anat & Neurobiol, 800 Rose St, Lexington, KY 40536 USA. EM khauser@uky.edu FU NIAAA NIH HHS [AA13486-03, U01 AA013486]; NIDA NIH HHS [DA13359, DA15097, R01 DA013559, R01 DA015097] NR 222 TC 55 Z9 56 U1 1 U2 3 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2005 VL 10 BP 216 EP 235 DI 10.2741/1522 PG 20 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 970OK UT WOS:000232319300023 PM 15574363 ER PT J AU Tonelli, LH Postolache, TT Sternberg, EM AF Tonelli, LH Postolache, TT Sternberg, EM TI Inflammatory genes and neural activity: Involvement of immune genes in synaptic function and behavior SO FRONTIERS IN BIOSCIENCE LA English DT Article DE tumor necrosis factor; fractalkine; glutamate; Glia; depression; neuroimmune; review ID CENTRAL-NERVOUS-SYSTEM; CLASS-I MHC; LONG-TERM POTENTIATION; MESSENGER-RNA; RAT-BRAIN; TNF-ALPHA; CEREBROSPINAL-FLUID; MULTIPLE-SCLEROSIS; BIPOLAR DISORDER; TRANSGENIC MICE AB The function of pro-inflammatory cytokines and chemokines in brain injury and autoimmune diseases has been long recognized. There is however, a significant lack of information regarding the role of constitutively expressed immune genes in the normal brain. The current evidence points to the involvement of certain cytokines and major histocompatibility complex (MHC) molecules in synaptic function and plasticity. Furthermore, constitutively expressed chemokines in neurons provide an additional indication of a role for these molecules in neural function. In addition, clinical data suggests a dysregulation of immune genes in the cerebrospinal fluid of psychiatric patients who have neither brain injury nor autoimmune diseases. This review will discuss recent data indicating a role for immune genes in synaptic stability and will also discuss the implications for specific brain functions involving mood and cognition. C1 NIMH, Sect Neuroendocrine Immunol & Behav, NIH, DHHS, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Psychiat, Mood & Anxiety Program, Baltimore, MD 21201 USA. RP Tonelli, LH (reprint author), NIMH, Sect Neuroendocrine Immunol & Behav, NIH, DHHS, 36 Convent Dr,Bldg 36,Room 1A21, Bethesda, MD 20892 USA. EM tonellil@irp.nimh.nih.gov NR 57 TC 25 Z9 28 U1 0 U2 2 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2005 VL 10 BP 675 EP 680 DI 10.2741/1562 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 970OK UT WOS:000232319300063 PM 15569608 ER PT J AU Abrams, SI AF Abrams, SI TI Positive and negative consequences of Fas/Fas ligand interactions in the antitumor response SO FRONTIERS IN BIOSCIENCE LA English DT Review DE cytotoxic T lymphocytes; Fas; Fas ligand; immunotherapy; neoplasia; tumor escape; immune system; cancer; gene; review ID FAS-MEDIATED APOPTOSIS; COLON-CARCINOMA CELLS; EFFECTOR T-CELLS; CTL ADOPTIVE IMMUNOTHERAPY; FLICE-INHIBITORY PROTEIN; PERFORIN-DEFICIENT MICE; ANTIGEN-LOSS VARIANTS; RENAL-CANCER CELLS; NF-KAPPA-B; TUMOR-REGRESSION AB Understanding the mechanisms by which T lymphocytes mediate antitumor activity in vivo may have important implications for the design of active, adoptive and combination immunotherapies against neoplastic progression. The Fas/Fas ligand ( FasL) system utilized by antigen (Ag)-specific T cells has been now demonstrated to play important roles in lymphocyte-mediated tumor regression in vivo. However, the process of tumor eradication by Fas/FasL interactions per se may serve also as an immune-based selective pressure. Indeed, more recent studies have illustrated that this same Fas/FasL system may have negative contributions, perhaps serving as a novel mechanism of tumor escape of Fas-resistant subpopulations. In addition to Fas-resistance, functional FasL expression by certain cancer cell types has been implicated in tumor escape via destruction of infiltrating Fas-bearing lymphocytes. Thus, the acquisition of Fas-resistance by advancing neoplastic subpopulations, possibly in combination with FasL induction may serve as countermeasures against immune attack and contribute favorably toward metastatic development. Further appreciation of the complex nature of this Fas/FasL system, exploited not only by innate or adaptive elements of the immune response, but also by a developing neoplasm may have important implications for the regulation of tumor progression in favor of clinical regression. Thus, this review will focus on both positive and negative consequences of the Fas/FasL system during host/tumor interactions. Emphasis will be on the importance of the Fas/FasL pathway for antitumor activity, as well as a potential selective force influencing the escape of Fas-resistant aggressive tumor variants. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Abrams, SI (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 5B46, Bethesda, MD 20892 USA. EM sa47z@nih.gov NR 124 TC 24 Z9 28 U1 0 U2 2 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2005 VL 10 BP 809 EP 821 DI 10.2741/1575 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 970OK UT WOS:000232319300076 PM 15569621 ER PT J AU Pise-Masison, CA Brady, JN AF Pise-Masison, CA Brady, JN TI Setting the stage for transformation: HTLV-1 tax inhibition of p53 function SO FRONTIERS IN BIOSCIENCE LA English DT Review DE HTLV-1; p53; tax; cancer; cell-cycle; review ID T-CELL LEUKEMIA; NF-KAPPA-B; VIRUS TYPE-I; TUMOR-SUPPRESSOR PROTEIN; ELEMENT-BINDING-PROTEIN; TRIOXIDE-INDUCED APOPTOSIS; PRIMARY HUMAN-LYMPHOCYTES; PROSTATE-CANCER CELLS; WILD-TYPE P53; TYPE-1 TAX AB Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia and tropical spastic paraparesis/ HTLV-1 associated myelopathy (TSP/HAM). Although the precise mechanism of HTLV-1 oncogenesis remains unclear, the pathogenesis has been linked to the pleiotropic activity of the viral transcriptional activator protein Tax. Tax has been shown to regulate viral and cellular gene expression and to functionally interfere with proteins involved in cell-cycle progression and DNA repair. This review will concentrate on the ability of Tax to promote cellular proliferation through activation of the NF-kappa B pathway while inhibiting the cell-cycle checkpoint and apoptotic function of the tumor suppressor gene p53. C1 NCI, Virus Tumor Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Brady, JN (reprint author), NCI, Virus Tumor Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bldg 41-B201,41 Lib Dr, Bethesda, MD 20892 USA. EM bradyj@dce41.nci.nih.gov NR 155 TC 18 Z9 18 U1 0 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2005 VL 10 BP 919 EP 930 DI 10.2741/1586 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 970OK UT WOS:000232319300087 PM 15569630 ER PT S AU Moreau-Villeger, V Delingette, H Sermesant, M Ashikaga, H Faris, O McVeigh, E Ayache, N AF Moreau-Villeger, V Delingette, H Sermesant, M Ashikaga, H Faris, O McVeigh, E Ayache, N BE Frangi, A Radeva, PI Santos, A Hernandez, M TI Estimating local apparent conductivity with a 2-D electrophysiological model of the heart SO FUNCTIONAL IMAGING AND MODELING OF HEART, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 3rd International Workshop on Functional Imaging and Modeling of the Heart CY JUN 02-04, 2005 CL Barcelona, SPAIN SP Autonomous Univ Barcelona, Pompeu Fabra Univ, Polytech Univ Madrid, Dept Univ, Recerca Soc Informac, Aragon Inst Engn Res, IEEE Spain Sect, Mol & /Multi-Modal Med Imaging Themat Network, IEEE Engn Med & Biol Soc, Minist Educ & Sci, Minist Hlth & Consumpt, MEDIS Med Imaging Syst B V, Medtronics, European Commiss DG-INFSO, Generalitat Catalunya, Barcelona City AB In this article we study the problem of estimating the parameters of a 2-D electrophysiological model of the heart from a set of temporal recordings of extracellular potentials. The chosen model is the reaction-diffusion model on the action potential proposed by Aliev and Panfilov. The strategy consists in building an error criterion based upon a comparison of depolarization times between the model and the measures. This error criterion is minimized in two steps : first a global and then a local adjustment of the model parameters. The feasibility of the approach is demonstrated on real measures on canine hearts, showing also the necessity to introduce anisotropy and probably a third spatial dimension in the model. C1 INRIA, EPIDAURE Res Project, Sophia Antipolis, France. Kings Coll London, Computat Imaging Sci Grp, London WC2R 2LS, England. NHLBI, Lab Cardiac Energet, NIH, Bethesda, MD 20892 USA. RP Moreau-Villeger, V (reprint author), INRIA, EPIDAURE Res Project, Sophia Antipolis, France. OI Sermesant, Maxime/0000-0002-6256-8350; Frangi, Alejandro/0000-0002-2675-528X NR 15 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-26161-3 J9 LECT NOTES COMPUT SC PY 2005 VL 3504 BP 256 EP 266 PG 11 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BCO07 UT WOS:000230370000026 ER PT S AU Schmidt, PJ AF Schmidt, PJ BE Singh, M Simpkins, JW TI Depression, the perimenopause, and estrogen therapy SO FUTURE OF HORMONE THERAPY: WHAT BASIC SCIENCE AND CLINICAL STUDIES TEACH US SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on the Future of Estrogen and Hormone Therapy Postmenopausal Women CY NOV 05-07, 2004 CL Ft Worth, TX SP Univ N Texas Hlth Sci Ctr DE perimenopause; depression; estrogen ID NATIONAL-COMORBIDITY-SURVEY; MESSENGER-RNA EXPRESSION; ELEMENT-BINDING PROTEIN; MOOD DISORDERS; POSTMENOPAUSAL WOMEN; OVARIECTOMIZED RATS; MAJOR DEPRESSION; MENTAL-DISORDERS; OVARIAN-STEROIDS; RECEPTOR-BINDING AB The focus of this chapter is the relationship between the onset of depression in women and the reproductive events of the perimenopause. The perimenopause is a time of considerable variability in reproductive function, which appears in some women to be associated with ail increased susceptibility to depression. Elevated gonadotropin levels occur during the late perimenopause, with plasma follicle-stimulating hormone levels increasing in association with impaired ovarian function and decreased estradiol secretion. It is unclear, however, whether the variability in ovarian hormone secretion during the perimenopause has a substantial causal role in the development of depression. Epidemiologic studies have documented that most women do not become depressed during the menopausal transition. However, recent longitudinal studies suggest that in some women, perimenopause-related reproductive events play a role in the onset of depression. Additionally, randomized controlled trials have documented the short-term (3-6 weeks) antidepressant efficacy of estradiol in depressed perimenopausal women. Thus, although depression is not a uniform accompaniment of the menopausal transition, in some women age-related changes in ovarian estrogen production may alter central nervous system function and predispose them to develop depression. C1 NIMH, Behav Endocrinol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Schmidt, PJ (reprint author), NIMH, Behav Endocrinol Branch, NIH, Dept Hlth & Human Serv, Bldg 10 CRC,Rm 6-5340,10 Ctr Dr,MSC 1276, Bethesda, MD 20892 USA. EM peterschmidt@mail.nih.gov NR 99 TC 27 Z9 29 U1 1 U2 7 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-584-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1052 BP 27 EP 40 DI 10.1196/annals.1347.003 PG 14 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Obstetrics & Gynecology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Obstetrics & Gynecology GA BDE44 UT WOS:000233076700003 PM 16024748 ER PT J AU Ruhl, CE Everhart, JE AF Ruhl, CE Everhart, JE TI Coffee and caffeine consumption reduce the risk of elevated serum alanine aminotransferase activity in the United States SO GASTROENTEROLOGY LA English DT Article ID GAMMA-GLUTAMYL-TRANSFERASE; AGED JAPANESE MEN; TYPE-2 DIABETES-MELLITUS; SELF-DEFENSE OFFICIALS; POPULATION DETERMINANTS; LIPID-PEROXIDATION; LIVER-CIRRHOSIS; LIFE-STYLE; ALCOHOL; DRINKING AB Background& Aims: Based on experimental and epidemiologic studies, we investigated whether coffee and caffeine consumption reduced the risk of elevated alanine aminotransferase (ALT) activity in persons at high risk for liver injury in a national, population-based study. Methods: Participants were 5944 adults in the Third US National Health and Nutrition Examination Survey, 1988-1994, with excessive alcohol consumption, viral hepatitis, iron overload, overweight, or impaired glucose metabolism. Liver injury was indicated by abnormal serum ALT activity (>43 U/L). Results : Elevated ALT activity was found in 8.7% of this high-risk population. In unadjusted analysis, lower ALT activity was associated with increasing consumption of coffee (P =.001) and caffeine (P =.001). Multivariate logistic regression analyses showed that the risk of elevated ALT activity declined with increasing intake of coffee (P for trend =.034) and caffeine (P <.001). Comparing persons who drank more than 2 cups per day with noncoffee drinkers, the odds ratio was.56 (95% confidence interval,.311.0). Comparing persons in the highest caffeine quintile with the lowest, the odds ratio was.31 (95% confidence interval,.16-.61). These relationships were consistent across subgroups at risk for liver injury and were relatively unchanged when analyses included the entire population or when limited to persons without impaired liver function or right upper quadrant pain. Fasting insulin concentrations did not mediate the effects. Conclusions: In this large, national, population-based study, among persons at high risk for liver injury, consumption of coffee and especially caffeine was associated with lower risk of elevated ALT activity. C1 Social & Sci Syst Inc, Silver Spring, MD 20910 USA. NIDDKD, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Ruhl, CE (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA. EM cruhl@s-3.com FU NIDDK NIH HHS [N01 DK 12478] NR 47 TC 129 Z9 134 U1 2 U2 13 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2005 VL 128 IS 1 BP 24 EP 32 DI 10.1053/j.gastro.2004.09.075 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 886KG UT WOS:000226225400007 PM 15633120 ER PT J AU Borm, MEA He, JP Kelsall, B Pena, AS Strober, W Bouma, G AF Borm, MEA He, JP Kelsall, B Pena, AS Strober, W Bouma, G TI A major quantitative trait locus on mouse chromosome 3 is involved in disease susceptibility in different colitis models SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; INTERLEUKIN-12 PRODUCTION; IL-10-DEFICIENT MICE; ULCERATIVE-COLITIS; GENE FAMILY; PROTEIN; IDENTIFICATION; RESPONSES; NOD2 AB Background& Aims: Mice with a disrupted gene for the G-protein alpha inhibitory 2 chain (Gnai2(-/-)) develop a spontaneous colitis resembling human inflammatory bowel disease. Disease expression differs markedly between inbred strains of mice, indicating genetic control of disease susceptibility. We performed a genome-wide screen to localize the chromosomal regions regulating disease expression. Methods: A total of 284 F2 mice derived from resistant C57BL/6J Gnai2(-/-) mice and susceptible C3H/HeN Gnai2(-/-) mice were analyzed in a genome-wide screen for colitis susceptibility and severity. Result : A highly significant locus on chromosome 3 (Gpdc1) contributed to colitis susceptibility and severity (likelihood ratio statistics [LRS] = 32.4; LOD score = 7; P < 1.0 X 10(-5)). The peak linkage of this locus at 62 cM colocalizes exactly with a previously identified locus controlling colitis susceptibility in interleukin-10 -deficient mice. In addition, evidence for linkage with a locus on chromosome 1 (Gpdc2; LIRS = :19.7; LOD = 4.3) was found, and the 2 loci interacted epistatically (combined LIRS = 68.2). A third locus (Gpdc3) was found on chromosome 9 and this locus interacted epistatically with a locus on chromosome 7, which by itself did not have an effect on the trait. Conclusions: The identification of a major locus on chromosome 3 that controls susceptibility to spontaneous colitis in 2 different gene-knockout models indicates that this locus harbors a gene(s) that plays a key role in maintaining mucosal homeostasis. Identification of this gene(s) may contribute to further understanding of the mechanisms underlying human inflammatory bowel disease. C1 Vrije Univ Amsterdam, Ctr Med, Immunogenet Lab, NL-1081 BT Amsterdam, Netherlands. NIAID, Immune Cell Interact Unit, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Bouma, G (reprint author), Vrije Univ Amsterdam, Ctr Med, Immunogenet Lab, Boechorststr 7,Room J393, NL-1081 BT Amsterdam, Netherlands. EM gbouma@niaid.nih.gov RI bouma, gerd/E-2520-2013 NR 29 TC 23 Z9 23 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2005 VL 128 IS 1 BP 74 EP 85 DI 10.1053/j.gastro.2004.10.044 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 886KG UT WOS:000226225400012 PM 15633125 ER PT J AU Bailey-Wilson, JE Almasy, L Edenberg, H Greenberg, DA Hansen, MST Kennedy, GC Thomas, D Pugh, EW MacCluer, JW AF Bailey-Wilson, JE Almasy, L Edenberg, H Greenberg, DA Hansen, MST Kennedy, GC Thomas, D Pugh, EW MacCluer, JW TI Genetic analysis workshop 14: Introduction to workshop summaries SO GENETIC EPIDEMIOLOGY LA English DT Editorial Material DE microsatellites; single-nucleotide polymorphism; SNP; STRP; genome-wide scan; association; linkage; haplotype; heterogeneity; data mining; interaction; parent of origin imprinting; mitochondrial; alcoholism ID ALCOHOL DEPENDENCE; LINKAGE DISEQUILIBRIUM; BRAIN POTENTIALS; RECEPTOR; GENOME; RECOMBINATION; OSCILLATIONS; ASSOCIATION; LOCI; EEG AB Genetic Analysis Workshop 14 (GAW14) was held September 7-10, 2005, in Noordwijkerhout, The Netherlands. The overarching theme was the comparison of microsatellite and single-nucleotide polymorphism (SNP) markers for genome-wide scans, and the statistical methods that can best exploit the information provided in such scans for linkage and association studies. The 183 contributions submitted to GAW14 were organized into 18 presentation groups of 7-15 papers each. GAW14 participants had the choice of two data sets to analyze. COGA generously donated extensive family data on alcoholism, related phenotypes, pertinent covariates, and a set of previously analyzed genomescan microsatellite marker genotypes. The simulated data were designed to have similarities to the real data set. Extensive new SNP genotyping was performed on DNA provided by COGA for the previously genotyped families. Illumina, Affymetrix, and the Center for Inherited Disease Research performed this work and donated these data to GAW14 and to COGA. The group summary papers collected in this issue present the major findings from GAW14. C1 NHGRI, NIH, Inherited Dis Res Branch, Baltimore, MD 21224 USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78284 USA. Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46204 USA. Columbia Presbyterian Med Ctr, Mailman Sch Publ Hlth, Dept Biostat, Div Stat Genet, New York, NY 10032 USA. Illumina Inc, San Diego, CA USA. Affymetrix Inc, Santa Clara, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Johns Hopkins Sch Med, Ctr Inherited Dis Res, Baltimore, MD USA. RP Bailey-Wilson, JE (reprint author), NHGRI, NIH, Inherited Dis Res Branch, 333 Cassell Dr,Suite 2000, Baltimore, MD 21224 USA. EM jebw@mail.nih.gov NR 22 TC 5 Z9 5 U1 3 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2005 VL 29 SU 1 BP S1 EP S6 DI 10.1002/gepi.20105 PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 000ZR UT WOS:000234502000001 ER PT J AU Beckmann, L Ziegler, A Duggal, P Bailey-Wilson, JE AF Beckmann, L Ziegler, A Duggal, P Bailey-Wilson, JE TI Haplotypes and haplotype-tagging single-nucleotide polymorphism: Presentation group 8 of genetic analysis workshop 14 SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 14th Genetic Analysis Workshop CY SEP 07-19, 2004 CL Noordwijkerhout, NETHERLANDS DE association analysis; genome-wide analysis; haplotype-sharing; haplotype-tagging; linkage analysis; single-nucleotide; polymorphism; multiple testing ID LINKAGE DISEQUILIBRIUM; GENOTYPE DATA; HUMAN GENOME; MANTEL STATISTICS; ASSOCIATION TEST; SHARING ANALYSIS; CANDIDATE GENES; BLOCKS; SNPS; RECOMBINATION AB Moderately dense maps of single-nucleotide polymorphism (SNP) markers across the human genome for both the simulated data set and data from the Collaborative Study of the Genetics of Alcoholism were available at Genetic Analysis Workshop 14 for the first time. This allowed examination of various novel and existing methods for haplotype analyses. Three contributors applied Mantel statistics in different ways for both linkage and association analysis by using the shared length between two haplotypes at a marker locus as a measure of genetic similarity. The results indicate that haplotype-sharing based on Mantel statistics can be a powerful approach and needs further methodological evaluation. Four contributors investigated haplotype-tagging SNP (htSNP) selection procedures, two contributors examined the use of multilocus haplotypes compared to single loci in association tests, and two contributors compared the accuracy of various methods for reconstructing haplotypes and estimating haplotype frequencies for both pedigree data and data from unrelated individuals. For all three different tasks, software packages and procedures gave similar results in regions of high linkage disequilibrium (LD). However, they were not as consistent in regions of moderate to low LD. One coalescence-based approach for estimating haplotype frequencies, coupled with a Markov chain Monte Carlo technique, outperformed the other haplotype frequency estimation methods in regions of low LD. In conclusion, regardless of the task, results were similar in chromosomal regions of high LD. However, based on the differing results observed here, methodological improvements are required for chromosomal regions of low to moderate LD. C1 NHGRI, NIH, Baltimore, MD 21224 USA. German Canc Res Ctr, Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. Med Univ Lubeck, Inst Med Biometry & Stat, D-23538 Lubeck, Germany. RP Bailey-Wilson, JE (reprint author), NHGRI, NIH, 333 Cassell Dr,Suite 2000, Baltimore, MD 21224 USA. EM jebw@mail.nih.gov RI Ziegler, Andreas/G-4246-2012; OI Ziegler, Andreas/0000-0002-8386-5397; Bailey-Wilson, Joan/0000-0002-9153-2920 FU Intramural NIH HHS NR 56 TC 8 Z9 8 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2005 VL 29 SU 1 BP S59 EP S71 DI 10.1002/gepi.20111 PG 13 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 000ZR UT WOS:000234502000007 PM 16342175 ER PT J AU Bickeboller, H Bailey, JN Papanicolaou, GJ Rosenberger, A Viel, KR AF Bickeboller, H Bailey, JN Papanicolaou, GJ Rosenberger, A Viel, KR TI Dissection of heterogeneous phenotypes for quantitative trait mapping SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 14th Genetic Analysis Workshop CY SEP 07-19, 2004 CL Noordwijkerhout, NETHERLANDS DE endophenotypes; multidimensional traits; recombination rate; pseudotrait; heritability; segregation; linkage; association; chip technology; genome-wide scan AB We discuss analyses of Genetic Analysis Workshop 14 data from the Collaborative Study on the Genetics of Alcoholism (COGA) as well as from a simulated complex disease, Kofendrerd personality disorder (KPD), with both genetic and phenotypic heterogeneity. Both data sets included numerous related phenotypes in addition to disease definitions. All analyses either chose from the given selection of phenotypes or defined new ones, including traits that may not have been related to alcoholism or KPD. Some contributors evaluated the genetic components of the trait. Many investigated genome-wide linkage and/or association, using microsatellites and/or single-nucleotide polymorphism (SNP) chip data. Here we will focus on methodological issues that the investigators faced. Their results depended on phenotype selection, whether continuous or discrete, the covariates included, and ethnicity of the study population. For SNP chip data, members of our group detected no difference in results for Affymetrix or Illumina chips, although higher marker density for association studies appeared to be advantageous. Overall, there were some observations that different chromosomal segments, i.e., physical locations on the p-arm, cl-arm, or middle segment, might lead to possible differences in type I error rates. This finding and others highlight the importance of empirical determination of P-values to determine significance. C1 Univ Gottingen, Dept Genet Epidemiol, D-37073 Gottingen, Germany. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. RP Bickeboller, H (reprint author), Univ Gottingen, Dept Genet Epidemiol, Humboldtallee 32, D-37073 Gottingen, Germany. EM hbickeb@gwdg.de NR 17 TC 1 Z9 1 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2005 VL 29 SU 1 BP S41 EP S47 DI 10.1002/gepi.20109 PG 7 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 000ZR UT WOS:000234502000005 PM 16342183 ER PT J AU Daw, EW Doan, BQ Elston, RC AF Daw, EW Doan, BQ Elston, RC TI Linkage mapping methods applied to the COGA data set: Presentation group 4 of genetic analysis workshop 14 SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 14th Genetic Analysis Workshop CY SEP 07-19, 2004 CL Noordwijkerhout, NETHERLANDS DE linkage analysis; alcoholism; affected-relative-pair linkage; SNP markers ID SCORE AB Presentation Group 4 participants analyzed the Collaborative Study on the Genetics of Alcoholism data provided for Genetic Analysis Workshop 14. This group examined various aspects of linkage analysis and related issues. Seven papers included linkage analyses, while the eighth calculated identity-by-descent (1131)) probabilities. Six papers analyzed linkage to an alcoholism phenotype: ALDX1 (four papers), ALDX2 (one paper), or a combination both (one paper). Methods used included Bayesian variable selection coupled with Haseman-Elston regression, recursive partitioning to identify phenotype and covariate groupings that interact with evidence for linkage, nonparametric linkage regression modeling, affected sib-pair linkage analysis with discordant sib-pair controls, simulation-based homozygosity mapping in a single pedigree, and application of a propensity score to collapse covariates in a general conditional logistic model. Alcoholism linkage was found with ! 2 of these approaches on chromosomes 2, 4, 6, 7, 9, 14, and 21. The remaining linkage paper compared the utility of several single-nucleotide polymorphism (SNP) and microsatellite marker maps for Monte Carlo Markov chain combined oligogenic segregation and linkage analysis, and analyzed one of the electrophysiological endophenotypes, ttth1, on chromosome 7. Linkage was found with all marker sets. The last paper compared the multipoint IBD information content of several SNP sets and the microsatellite set, and found that while all SNP sets examined contained more information than the microsatellite set, most of the information contained in the SNP sets was captured by a subset of the SNP markers with similar to 1-cM marker spacing. From these papers, we highlight three points: a 1-cM SNP map seems to capture most of the linkage information, so denser maps do not appear necessary; careful and appropriate use of covariates can aid linkage analysis; and sources of increased gene-sharing between relatives should be accounted for in analyses. C1 Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Univ Texas, Grad Sch Biomed Sci, Program Human & Mol Genet, Houston, TX USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NHGRI, Stat Genet Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. RP Daw, EW (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM warwick@request.mdacc.tmc.edu NR 25 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2005 VL 29 SU 1 BP S29 EP S34 DI 10.1002/gepi.20107 PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 000ZR UT WOS:000234502000003 PM 16342182 ER PT J AU Bielinska, B Lu, JM Sturgill, D Oliver, B AF Bielinska, B Lu, JM Sturgill, D Oliver, B TI Core promoter sequences contribute to ovo-B regulation in the Drosophila melanogaster germline SO GENETICS LA English DT Article ID LINE SEX DETERMINATION; OVARIAN-TUMOR; EPIDERMIS DIFFERENTIATION; GENE; TRANSCRIPTION; SIGNALS; LOCUS; OOGENESIS; SELECTION; DEPENDS AB Utilization of tightly linked ovo-A vs. ovo-B germline promoters results in the expression of OVO-A and OVO-B, C,H transcription factors with different N-termini, and different effects on target gene transcription and on female germline development. We show that two sex-determination signals, the X chromosome number within the germ cells and a female soma, differentially regulate ovo-B and ovo-A. We have previously shown that OVO regulates ovarian tumor transcription by binding the transcription start site. We have explored the regulation of the ovo-B promoter using an extensive series of transgenic reporter gene constructs to delimit cis-regulatory sequences as assayed in wild-type and sex-transformed flies and flies with altered ovo dose. Minimum regulated expression of ovo-B requires a short region flanking the transcription start site, Suggesting that the ovo-B core promoter bears regulatory information in addition to a "basal" activity. In support of this idea, the core promoter region binds distinct factors in ovary and testis extracts, but not in soma extracts, suggesting that regulatory complexes form at the start site. This idea is further supported by the evolutionarily conserved organization of OVO binding sites at or near the start sites of ovo loci in other flies. C1 NIDDK, LCDB, NIH, DHHS, Bethesda, MD 20892 USA. RP Oliver, B (reprint author), NIDDK, LCDB, NIH, DHHS, 50 S Dr,MSC 8028,Bldg 50,Room 3339, Bethesda, MD 20892 USA. EM oliver@helix.nih.gov FU NIDDK NIH HHS [Z01 DK015600-10] NR 39 TC 11 Z9 11 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JAN PY 2005 VL 169 IS 1 BP 161 EP 172 DI 10.1534/genetics.104.033118 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 897XJ UT WOS:000227039900014 PM 15371353 ER PT J AU Carter, MG Sharov, AA VanBuren, V Dudekula, DB Carmack, CE Nelson, C Ko, MSH AF Carter, MG Sharov, AA VanBuren, V Dudekula, DB Carmack, CE Nelson, C Ko, MSH TI Transcript copy number estimation using a mouse whole-genome oligonucleotide microarray SO GENOME BIOLOGY LA English DT Article ID 3 ABUNDANCE CLASSES; GENE-EXPRESSION; MESSENGER-RNA; STEM-CELLS; COMPLEXITY; REPOSITORY; ARRAY; TOOL AB The ability to quantitatively measure the expression of all genes in a given tissue or cell with a single assay is an exciting promise of gene-expression profiling technology. An in situ-synthesized 60-mer oligonucleotide microarray designed to detect transcripts from all mouse genes was validated, as well as a set of exogenous RNA controls derived from the yeast genome ( made freely available without restriction), which allow quantitative estimation of absolute endogenous transcript abundance. C1 NIA, Dev Genom & Aging Sect, Genet Lab, Baltimore, MD 21224 USA. Agilent Technol, Palo Alto, CA 94304 USA. RP Ko, MSH (reprint author), NIA, Dev Genom & Aging Sect, Genet Lab, 333 Cassell Dr, Baltimore, MD 21224 USA. EM kom@mail.nih.gov RI Carter, Mark/B-5089-2010; Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 28 TC 79 Z9 82 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2005 VL 6 IS 7 AR R61 DI 10.1186/gb-2005-6-7-r61 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 957GR UT WOS:000231358300015 PM 15998450 ER PT J AU Desiere, F Deutsch, EW Nesvizhskii, AI Mallick, P King, NL Eng, JK Aderem, A Boyle, R Brunner, E Donohoe, S Fausto, N Hafen, E Hood, L Katze, MG Kennedy, KA Kregenow, F Lee, HK Lin, BY Martin, D Ranish, JA Rawlings, DJ Samelson, LE Shiio, Y Watts, JD Wollscheid, B Wright, ME Yan, W Yang, LH Yi, EC Zhang, H Aebersold, R AF Desiere, F Deutsch, EW Nesvizhskii, AI Mallick, P King, NL Eng, JK Aderem, A Boyle, R Brunner, E Donohoe, S Fausto, N Hafen, E Hood, L Katze, MG Kennedy, KA Kregenow, F Lee, HK Lin, BY Martin, D Ranish, JA Rawlings, DJ Samelson, LE Shiio, Y Watts, JD Wollscheid, B Wright, ME Yan, W Yang, LH Yi, EC Zhang, H Aebersold, R TI Integration with the human genome of peptide sequences obtained by high-throughput mass spectrometry SO GENOME BIOLOGY LA English DT Article ID STATISTICAL-MODEL; PROTEOMICS; IDENTIFICATION; PROTEIN; DATABASE; ANNOTATION; ACCURACY; SEARCH; GENES; TOOLS AB A crucial aim upon the completion of the human genome is the verification and functional annotation of all predicted genes and their protein products. Here we describe the mapping of peptides derived from accurate interpretations of protein tandem mass spectrometry ( MS) data to eukaryotic genomes and the generation of an expandable resource for integration of data from many diverse proteomics experiments. Furthermore, we demonstrate that peptide identifications obtained from high-throughput proteomics can be integrated on a large scale with the human genome. This resource could serve as an expandable repository for MS-derived proteome information. C1 Inst Syst Biol, Seattle, WA 98103 USA. Nestle Res Ctr, CH-1000 Lausanne 26, Switzerland. Univ Zurich, Inst Zool, CH-8057 Zurich, Switzerland. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. NCI, Bethesda, MD 20892 USA. N Shore Long Isl Jewish Res Inst, Manhasset, NY 11030 USA. ETH Honggerberg, Swiss Fed Inst Technol, Inst Biotechnol, CH-8093 Zurich, Switzerland. RP Aebersold, R (reprint author), Inst Syst Biol, 1441 N 34th St, Seattle, WA 98103 USA. EM ruedi@systemsbiology.org RI Nesvizhskii, Alexey/A-5410-2012; Eng, Jimmy/I-4202-2012; Wollscheid, Bernd/E-8909-2010; Eng, Jimmy/C-6556-2017 OI Nesvizhskii, Alexey/0000-0002-2806-7819; Eng, Jimmy/0000-0001-6352-6737; Wollscheid, Bernd/0000-0002-3923-1610; Eng, Jimmy/0000-0001-6352-6737 FU NHLBI NIH HHS [N01HV28179, N01-HV-28179]; NIAID NIH HHS [R01 AI051344, R01-AI-51344-01]; NIDA NIH HHS [P30 DA015625, P30DA015625] NR 34 TC 180 Z9 186 U1 1 U2 8 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 2005 VL 6 IS 1 AR R9 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 887WW UT WOS:000226337200015 PM 15642101 ER PT J AU Goldberg, IG Allan, C Burel, JM Creager, D Falconi, A Hochheiser, H Johnston, J Mellen, J Sorger, PK Swedlow, JR AF Goldberg, IG Allan, C Burel, JM Creager, D Falconi, A Hochheiser, H Johnston, J Mellen, J Sorger, PK Swedlow, JR TI The Open Microscopy Environment (OME) Data Model and XML file: open tools for informatics and quantitative analysis in biological imaging SO GENOME BIOLOGY LA English DT Article ID AUTOMATED INTERPRETATION; CELLS; PATTERNS AB The Open Microscopy Environment (OME) defines a data model and a software implementation to serve as an informatics framework for imaging in biological microscopy experiments, including representation of acquisition parameters, annotations and image analysis results. OME is designed to support high-content cell-based screening as well as traditional image analysis applications. The OME Data Model, expressed in Extensible Markup Language (XML) and realized in a traditional database, is both extensible and self-describing, allowing it to meet emerging imaging and analysis needs. C1 Univ Dundee, Div Gene Regulat & Express, Dundee DD1 5EH, Scotland. NIA, Image Informat & Computat Biol Unit, Genet Lab, NIH, Baltimore, MD 21224 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Swedlow, JR (reprint author), Univ Dundee, Div Gene Regulat & Express, Dow St, Dundee DD1 5EH, Scotland. EM jason@lifesci.dundee.ac.uk RI Goldberg, Ilya/H-5307-2011 OI Goldberg, Ilya/0000-0001-8514-6110 FU NIGMS NIH HHS [P50 GM068762, GM068762] NR 34 TC 93 Z9 96 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2005 VL 6 IS 5 AR R47 DI 10.1186/gb-2005-6-5-r47 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 922UI UT WOS:000228864300014 PM 15892875 ER PT J AU Hondo, E Stewart, CL AF Hondo, E Stewart, CL TI Profiling gene expression in growth-arrested mouse embryos in diapause SO GENOME BIOLOGY LA English DT Review ID LEUKEMIA INHIBITORY FACTOR; STEM-CELLS; TARGETED DISRUPTION; EGF-RECEPTOR; IMPLANTATION; EMBRYOGENESIS; BLASTOCYSTS; CYTOKINES; ESTROGEN; PROTEIN AB In many mammalian species, embryonic cell proliferation can be reversibly arrested in an embryonic diapause at the time of embryo implantation. A recent report has identified changes in embryonic gene expression that are associated with, and may halt, embryonic cell proliferation. C1 NCI, Canc & Dev Biol Lab, Div Basic Sci, Frederick, MD 21702 USA. RP Stewart, CL (reprint author), NCI, Canc & Dev Biol Lab, Div Basic Sci, Frederick, MD 21702 USA. EM stewartc@ncifcrf.gov NR 24 TC 15 Z9 17 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2005 VL 6 IS 1 AR 202 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 887WW UT WOS:000226337200003 PM 15642106 ER PT J AU Huang, SX Li, Y Chen, YD Podsypanina, K Chamorro, M Olshen, AB Desai, KV Tann, A Petersen, D Green, JE Varmus, HE AF Huang, SX Li, Y Chen, YD Podsypanina, K Chamorro, M Olshen, AB Desai, KV Tann, A Petersen, D Green, JE Varmus, HE TI Changes in gene expression during the development of mammary tumors in MMTV-Wnt-1 transgenic mice SO GENOME BIOLOGY LA English DT Article ID HUMAN-BREAST-CANCER; BETA-CATENIN; RETINOIC ACID; SYNERGISTIC INDUCTION; PROGENITOR CELLS; CYCLIN D1; C-MYC; PATHWAY; IDENTIFICATION; PROGRESSION AB Background: In human breast cancer normal mammary cells typically develop into hyperplasia, ductal carcinoma in situ, invasive cancer, and metastasis. The changes in gene expression associated with this stepwise progression are unclear. Mice transgenic for mouse mammary tumor virus (MMTV)-Wnt-1 exhibit discrete steps of mammary tumorigenesis, including hyperplasia, invasive ductal carcinoma, and distant metastasis. These mice might therefore be useful models for discovering changes in gene expression during cancer development. Results: We used cDNA microarrays to determine the expression profiles of five normal mammary glands, seven hyperplastic mammary glands and 23 mammary tumors from MMTV-Wnt-1 transgenic mice, and 12 mammary tumors from MMTV-Neu transgenic mice. Adipose tissues were used to control for fat cells in the vicinity of the mammary glands. In these analyses, we found that the progression of normal virgin mammary glands to hyperplastic tissues and to mammary tumors is accompanied by differences in the expression of several hundred genes at each step. Some of these differences appear to be unique to the effects of Wnt signaling; others seem to be common to tumors induced by both Neu and Wnt-1 oncogenes. Conclusion: We described gene-expression patterns associated with breast-cancer development in mice, and identified genes that may be significant targets for oncogenic events. The expression data developed provide a resource for illuminating the molecular mechanisms involved in breast cancer development, especially through the identification of genes that are critical in cancer initiation and progression. C1 Sloan Kettering Inst, Program Canc Biol & Genet, New York, NY 10021 USA. Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Cell & Mol Biol, Houston, TX 77030 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. NCI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Singapore Ltd, Nanos, Singapore 138669, Singapore. RP Huang, SX (reprint author), Sloan Kettering Inst, Program Canc Biol & Genet, New York, NY 10021 USA. EM shixiah@bcm.tmc.edu FU NCI NIH HHS [P01 CA094060, P01 CA94060-02] NR 47 TC 28 Z9 29 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2005 VL 6 IS 10 AR R84 DI 10.1186/gb-2005-6-10-r84 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 975RM UT WOS:000232679600007 PM 16207355 ER PT J AU Nagorsen, D Deola, S Smith, K Wang, E Monsurro, V Zanovello, P Marincola, FM Panelli, MC AF Nagorsen, D Deola, S Smith, K Wang, E Monsurro, V Zanovello, P Marincola, FM Panelli, MC TI Polarized monocyte response to cytokine stimulation SO GENOME BIOLOGY LA English DT Article ID I INTERFERON RECEPTOR; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; GENE-EXPRESSION; MATRIX METALLOPROTEINASES; MONONUCLEAR PHAGOCYTES; GAP-JUNCTIONS; NITRIC-OXIDE; CELL-LINES; MACROPHAGES AB Background: Mononuclear phagocytes (MPs) stand at the crossroads between the induction of acute inflammation to recruit and activate immune effector cells and the downmodulation of the inflammatory process to contain collateral damage. This decision is extensively modulated by the cytokine microenvironment, which includes a broad array of cytokines whose direct effect on MPs remains largely unexplored. Therefore, we tested whether polarized responses of MPs to pathogens are related to the influence of selected cytokines or represent a mandatory molecular switch through which most cytokines operate. Results: Circulating CD14(+) MPs were exposed to bacterial lipopolysaccharide (LPS) followed by exposure to an array of cytokines, chemokines and soluble factors involved in the immune response. Gene expression was studied by global transcript analysis. Two main classes of cytokines were identified that induced a classical or an alternative pathway of MP activation. Expression of genes affected by NFkappaB activation was most predictive of the two main classes, suggesting that this pathway is a fundamental target of cytokine regulation. As LPS itself induces a classical type of activation, the most dramatic modulation was observed toward the alternative pathway, suggesting that a broad array of cytokines may counteract the pro-inflammatory effects of bacterial components. Conclusions: This analysis is directly informative of the primary effect of individual cytokines on the early stages of LPS stimulation and, therefore, may be most informative of the way MP maturation may be polarized at the early stages of the immune response. C1 NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Univ Padua, Dept Oncol & Surg Sci, Oncol Sect, I-35100 Padua, Italy. RP Panelli, MC (reprint author), NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. EM Mpanelli@mail.cc.nih.gov NR 42 TC 13 Z9 13 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2005 VL 6 IS 2 AR R15 DI 10.1186/gb-2005-6-2-r15 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 897SX UT WOS:000227026500011 PM 15693944 ER PT J AU Oliver, B Misteli, T AF Oliver, B Misteli, T TI A non-random walk through the genome SO GENOME BIOLOGY LA English DT Review ID GENE-EXPRESSION; DROSOPHILA-MELANOGASTER; NUCLEAR-ORGANIZATION; CHROMOSOMAL DOMAINS; COEXPRESSED GENES; CHROMATIN DOMAINS; ADJACENT GENES; X-CHROMOSOME; CELL-NUCLEI; INTERPHASE AB Recent publications on a wide range of eukaryotes indicate that genes showing particular expression patterns are not randomly distributed in the genome but are clustered into contiguous regions that we call neighborhoods. It seems probable that this organization is related to chromatin and the structure of the nucleus. C1 NIDDKD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Oliver, B (reprint author), NIDDKD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM oliver@helix.nih.gov; mistelit@mail.nih.gov NR 63 TC 30 Z9 30 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2005 VL 6 IS 4 AR 214 DI 10.1186/gb-2005-6-4-214 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 917DK UT WOS:000228436000003 PM 15833129 ER PT J AU Quignon, P Giraud, M Rimbault, M Lavigne, P Tacher, S Morin, E Retout, E Valin, AS Lindblad-Toh, K Nicolas, J Galibert, F AF Quignon, P Giraud, M Rimbault, M Lavigne, P Tacher, S Morin, E Retout, E Valin, AS Lindblad-Toh, K Nicolas, J Galibert, F TI The dog and rat olfactory receptor repertoires SO GENOME BIOLOGY LA English DT Article ID ODORANT RECEPTOR; FUNCTIONAL EXPRESSION; GENE SUPERFAMILY; XENOPUS-LAEVIS; MOUSE; IDENTIFICATION; SEQUENCE; GENOME; FAMILY; DISCRIMINATION AB Background: Dogs and rats have a highly developed capability to detect and identify odorant molecules, even at minute concentrations. Previous analyses have shown that the olfactory receptors (ORs) that specifically bind odorant molecules are encoded by the largest gene family sequenced in mammals so far. Results: We identified five amino acid patterns characteristic of ORs in the recently sequenced boxer dog and brown Norway rat genomes. Using these patterns, we retrieved 1,094 dog genes and 1,493 rat genes from these shotgun sequences. The retrieved sequences constitute the olfactory receptor repertoires of these two animals. Subsets of 20.3% ( for the dog) and 19.5% ( for the rat) of these genes were annotated as pseudogenes as they had one or several mutations interrupting their open reading frames. We performed phylogenetic studies and organized these two repertoires into classes, families and subfamilies. Conclusion: We have established a complete or almost complete list of OR genes in the dog and the rat and have compared the sequences of these genes within and between the two species. Our results provide insight into the evolutionary development of these genes and the local amplifications that have led to the specific amplification of many subfamilies. We have also compared the human and rat ORs with the human and mouse OR repertoires. C1 Univ Rennes 1, Genet & Dev CNRS, UMR 6061, F-35043 Rennes, France. IRISA, F-35042 Rennes, France. MIT, Broad Inst, Cambridge, MA 02141 USA. Harvard Univ, Cambridge, MA 02141 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Galibert, F (reprint author), Univ Rennes 1, Genet & Dev CNRS, UMR 6061, F-35043 Rennes, France. EM francis.galibert@univ-rennes1.fr NR 42 TC 74 Z9 78 U1 4 U2 20 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2005 VL 6 IS 10 AR R83 DI 10.1186/gb-2005-6-10-r83 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 975RM UT WOS:000232679600006 PM 16207354 ER PT J AU Tasneem, A Iyer, LM Jakobsson, E Aravind, L AF Tasneem, A Iyer, LM Jakobsson, E Aravind, L TI Identification of the prokaryotic ligand-gated ion channels and their implications for the mechanisms and origins of animal Cys-loop ion channels SO GENOME BIOLOGY LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; SECONDARY STRUCTURE PREDICTION; MULTIPLE SEQUENCE ALIGNMENT; HORIZONTAL GENE-TRANSFER; MAXIMUM-LIKELIHOOD; GLYCINE RECEPTOR; AGONIST-BINDING; GABA(A) RECEPTOR; DOMAIN; SUPERFAMILY AB Background: Acetylcholine receptor type ligand-gated ion channels (ART-LGIC; also known as Cys-loop receptors) are a superfamily of proteins that include the receptors for major neurotransmitters such as acetylcholine, serotonin, glycine, GABA, glutamate and histamine, and for Zn2+ ions. They play a central role in fast synaptic signaling in animal nervous systems and so far have not been found outside of the Metazoa. Results: Using sensitive sequence-profile searches we have identified homologs of ART-LGICs in several bacteria and a single archaeal genus, Methanosarcina. The homology between the animal receptors and the prokaryotic homologs spans the entire length of the former, including both the ligand-binding and channel-forming transmembrane domains. A sequence-structure analysis using the structure of Lymnaea stagnalis acetylcholine-binding protein and the newly detected prokaryotic versions indicates the presence of at least one aromatic residue in the ligand-binding boxes of almost all representatives of the superfamily. Investigation of the domain architectures of the bacterial forms shows that they may often show fusions with other small-molecule-binding domains, such as the periplasmic binding protein superfamily I (PBP-I), Cache and MCP-N domains. Some of the bacterial forms also occur in predicted operons with the genes of the PBP-II superfamily and the Cache domains. Analysis of phyletic patterns suggests that the ART-LGICs are currently absent in all other eukaryotic lineages except animals. Moreover, phylogenetic analysis and conserved sequence motifs also suggest that a subset of the bacterial forms is closer to the metazoan forms. Conclusions: From the information from the bacterial forms we infer that cation-pi or hydrophobic interactions with the ligand are likely to be a pervasive feature of the entire superfamily, even though the individual residues involved in the process may vary. The conservation pattern in the channel-forming transmembrane domains also suggests similar channel-gating mechanisms in the prokaryotic versions. From the distribution of charged residues in the prokaryotic M2 transmembrane segments, we expect that there will be examples of both cation and anion selectivity within the prokaryotic members. Contextual connections suggest that the prokaryotic forms may function as chemotactic receptors for low molecular weight solutes. The phyletic patterns and phylogenetic relationships suggest the possibility that the metazoan receptors emerged through an early lateral transfer from a prokaryotic source, before the divergence of extant metazoan lineages. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Illinois, Beckman Inst, Urbana, IL 61801 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM aravind@ncbi.nlm.nih.gov NR 62 TC 135 Z9 136 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2005 VL 6 IS 1 AR R4 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 887WW UT WOS:000226337200010 PM 15642096 ER PT J AU Sambrook, JG Bashirova, A Palmer, S Sims, S Trowsdale, J Abi-Rached, L Parham, P Carrington, M Beck, S AF Sambrook, JG Bashirova, A Palmer, S Sims, S Trowsdale, J Abi-Rached, L Parham, P Carrington, M Beck, S TI Single haplotype analysis demonstrates rapid evolution of the killer immunoglobulin-like receptor (KIR) loci in primates SO GENOME RESEARCH LA English DT Article ID IG-LIKE RECEPTORS; NK CELL-RECEPTOR; SEQUENCE-ANALYSIS; MULTIGENE FAMILY; RHESUS-MONKEY; GENE FAMILIES; LY49 GENES; MHC; DIVERSITY; SOFTWARE AB The human killer immnoglobulin-like receptors (KIR) are encoded within the Leukocyte Receptor Complex (LRC) on chromosome 19ql3.4. Here we report the comparative genomic analysis of single KIR haplotypes in two other primates. In the common chimpanzee (Pan troglodytes), seven KIR genes (ptKIRnewI, ptKIRnewII, ptKIR2DL5, ptKIRnewIII, ptKIR3DPI, ptKIR2DL4, ptKIR3DL1/2) have been identified, and five KIR genes (mmKIRnew1, mmKIR1D, mmKIR2DL4, mmKIR3DL10, mmKIR3L1) are present in the haplotype sequenced for the rhesus macaque (Macaca mulatta). Additional cDNA analysis confirms the genes predicted from the genomic sequence and reveals the presence of a fifth novel KIR gene (mmKIRnewII) in the second haplotype of the rhesus macaque. While all known human haplotypes contain both activating and inhibitory KIR genes, only inhibitory KIR genes (characterized by long cytoplasmic tails) were found by in silico and cDNA analyses in the two primate haplotypes Studied here. Comparison of the two human and the two non-human primate haplotypes demonstrates rapid diversification of the KIR gene family members, many of which have diverged in a species-specific manner. An analysis of the intronic regions of the two non-human primates reveals the presence of ancient repeat elements, which are indicative of the duplication events that have taken place since the last common ancestor. C1 Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. NCI, Lab Genome Divers, Frederick, MD 21702 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. Univ Cambridge, Dept Pathol, Div Immunol, Cambridge CB2 1QP, England. Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Microbiol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Immunol, Stanford, CA 94305 USA. RP Beck, S (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England. EM beck@sanger.ac.uk RI Abi-Rached, Laurent/H-7236-2012 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 49 TC 80 Z9 81 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JAN PY 2005 VL 15 IS 1 BP 25 EP 35 DI 10.1101/gr.2381205 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 885QB UT WOS:000226170900003 PM 15632087 ER PT J AU Kellner, WA Sullivan, RT Carlson, BH Thomas, JW AF Kellner, WA Sullivan, RT Carlson, BH Thomas, JW CA NISC Comp Sequ Prog TI Uprobe: A genome-wide universal probe resource for comparative physical mapping in vertebrates SO GENOME RESEARCH LA English DT Article ID PLACENTAL MAMMAL RADIATION; HOXA CLUSTER; MOUSE GENOME; SEQUENCE; PHYLOGENY; EVOLUTION; IDENTIFICATION; GENE; MAPS; RESOLUTION AB Interspecies comparisons are important for deciphering the functional content and evolution of genomes. The expansive array of >70 public vertebrate genomic bacterial artificial chromosome (BAC) libraries can provide a means of comparative mapping, sequencing, and functional analysis of targeted chromosomal segments that is independent and complementary to whole-genome sequencing. However, at the present time, no complementary resource exists for the efficient targeted physical mapping of the majority of these BAC libraries. Universal overgo-hybridization probes, designed from regions of sequenced genomes that are highly conserved between species, have been demonstrated to be an effective resource for the isolation of orthologous regions from multiple BAC libraries in parallel. Here we report the application of the universal probe design principal across entire genomes, and the Subsequent creation of a complementary probe resource, Uprobe, for screening vertebrate BAC libraries. Uprobe currently consists of whole-genome sets of universal overgo-hybridization probes designed for screening mammalian or avian/reptilian libraries. Retrospective analysis, experimental validation of the probe design process on a panel of representative BAC libraries, and estimates of probe coverage across the genome indicate that the majority of all eutherian and avian/reptilian genes or regions of interest can be isolated using Uprobe. Future implementation of the universal probe design strategy will be used to create an expanded number of whole-genome probe sets that will encompass all vertebrate genomes. C1 Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA. NHGRI, NIH, Genome Technol Branch, Bethesda, MD 20892 USA. NHGRI, NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA. RP Thomas, JW (reprint author), Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA. EM jthomas@genetics.emory.edu FU NIMH NIH HHS [MH068185, U01 MH068185] NR 44 TC 20 Z9 23 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JAN PY 2005 VL 15 IS 1 BP 166 EP 173 DI 10.1101/gr.3066805 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 885QB UT WOS:000226170900017 PM 15590945 ER PT J AU Anisimova, VN Ukraintseva, SV Anikin, IV Popovich, IG Zabezhinski, MA Bertsein, LM Arutjunyan, AV Ingram, DK Lane, MA Roth, GS AF Anisimova, VN Ukraintseva, SV Anikin, IV Popovich, IG Zabezhinski, MA Bertsein, LM Arutjunyan, AV Ingram, DK Lane, MA Roth, GS TI Effects of phentermine and phenformin on biomarkers of aging in rats SO GERONTOLOGY LA English DT Article DE caloric restriction; caloric restriction mimetics; appetite; body temperature; reactive oxygen species ID LIFE-SPAN; CAENORHABDITIS-ELEGANS; DIETARY RESTRICTION; CALORIE RESTRICTION; REGULATES LONGEVITY; SPONTANEOUS TUMORS; ENERGY-INTAKE; WEIGHT-LOSS; DISEASE; PROTEIN AB Background: Caloric restriction (CR) is the only treatment known to substantially prolong both average and maximal life span in experimental animals. Interventions that mimic certain effects of CR could be potential anti-aging treatments in humans. Drugs which reduce appetite (anorexiants) represent one class of candidate treatments. Agents that reduce the glucose utilization by the organism could also represent another class of candidate CR mimetics. Objective: In our study, we addressed the following questions: ( 1) Does treatment with an anorexiant reduce caloric intake and body weight of experimental animals comparable to that caused by CR? (2) Does treatment with an antidiabetic agent influence caloric intake and body weight? ( 3) Does treatment with any of these drugs affect metabolic parameters of an organism in the way similar to that observed with CR? Methods: One hundred and twenty 6-month-old female Wistar-derived LIO rats were randomly subdivided into four groups and exposed to: ( 1) ad libitum feeding with placebo ( controls); (2) the antidiabetic drug phenformin (2 mg/kg); (3) the anorectic drug phentermine (1 mg/kg), and (4) the same amount of food as the group with the least food intake during the previous week (pair-fed controls). Food and water intake, body weight, and rectal temperature were measured weekly during 16 weeks. At the end of the 16th week of the experiment, serum levels of glucose, total beta-lipoprotein and pre-beta-lipoprotein fractions, cholesterol, triglycerides, insulin, total triiodothyronine, and free thyroxine were estimated. The contents of diene conjugates and Schiff's bases, total antioxidant activity, the activities of Cu/Zn superoxide dismutase, glutathione S-transferase, and glutathione peroxidase, and the generation of reactive oxygen species (ROS) were studied in brain and liver homogenates and in the serum. Results: The controls exposed to pair feeding had a significantly reduced food consumption (about 20%) as compared with the ad libitum fed controls and thus exhibited a moderate CR. Treatment with phentermine reduced the caloric intake by about 12% as compared with the ad libitum fed controls. Body weight and water intake in this group were only slightly decreased ( by about 2 and 5%, respectively) as compared with the controls. The mean rectal temperature in the phentermine group (38degreesC) was significantly higher than in the ad libitum fed (37.8degreesC) and pair-fed (37.6degreesC) controls. Treatment with phentermine also resulted in significantly reduced ROS levels in all tissues studied, while the highest ROS production was found in ad libitum (blood serum) and pair-fed ( brain) controls. Treatment with phenformin did not significantly influence food and water consumption, body weight, and temperature when compared with the ad libitum fed controls. Rats treated with this antidiabetic drug showed intermediate values of ROS generation. Differences among the groups in total antioxidant activity were not obvious. Conclusions: Treatment with phentermine reduces caloric intake slightly less than is commonly observed in CR studies. CR due to forcibly reduced feeding and CR due to substance-suppressed appetite appear to act through different metabolic mechanisms and thus may affect aging and longevity in different ways. Copyright (C) 2005 S. Karger AG, Basel. C1 NN Petrov Res Inst Gerontol, Lab Carcinogenesis & Aging, St Petersburg 197758, Russia. DO Ott Res Inst Obstet & Gynecol, Lab Perinatal Biochem, St Petersburg, Russia. Duke Univ, Ctr Demog Res, Durham, NC USA. NIA, Lab Expt Gerontol, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Anisimova, VN (reprint author), NN Petrov Res Inst Gerontol, Lab Carcinogenesis & Aging, Pesochny 2, St Petersburg 197758, Russia. EM aging@mail.ru NR 57 TC 12 Z9 13 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0304-324X J9 GERONTOLOGY JI Gerontology PY 2005 VL 51 IS 1 BP 19 EP 28 DI 10.1159/000081430 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 883LH UT WOS:000226012800004 PM 15591752 ER PT J AU Bondy, CA Zhou, J AF Bondy, CA Zhou, J TI Growth hormone, insulin-like growth factors and the female reproductive system SO GROWTH HORMONE/INSULIN-LIKE GROWTH FACTOR AXIS DURING DEVELOPMENT SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article DE endometrium; IGFBP; IGF receptor; oocyte; ovary; steriodogenesis; uterus ID I IGF-I; MESSENGER-RIBONUCLEIC-ACID; RECEPTOR GENE-EXPRESSION; FACTOR-BINDING PROTEIN-1; SEX STEROID REGULATION; PRIMATE OVARY; FOLLICLE DEVELOPMENT; SIGNALING PATHWAYS; RAT OVARY; CELLULAR-LOCALIZATION C1 NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NR 70 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2005 VL 567 BP 91 EP 115 PG 25 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BDN28 UT WOS:000234425900004 PM 16370137 ER PT J AU Fernandez, AM LeRoith, D AF Fernandez, AM LeRoith, D TI Skeletal muscle SO GROWTH HORMONE/INSULIN-LIKE GROWTH FACTOR AXIS DURING DEVELOPMENT SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article DE myoblast; myotube; myofiber; regeneration; targeted knockout ID GROWTH-FACTOR-I; MESSENGER-RIBONUCLEIC-ACID; INSULIN-RECEPTOR SUBSTRATE-1; IGF-BINDING-PROTEIN; LONGITUDINAL BONE-GROWTH; STIMULATES TYROSINE PHOSPHORYLATION; DEPENDENT DIABETES-MELLITUS; HORMONE-RELEASING FACTOR; GENE-EXPRESSION; HYPOPHYSECTOMIZED RATS C1 CSIC, Inst Cajal, Unidad Plasticidad Neural, E-28002 Madrid, Spain. NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Fernandez, AM (reprint author), CSIC, Inst Cajal, Unidad Plasticidad Neural, Plaza Murillo 2, E-28002 Madrid, Spain. NR 197 TC 2 Z9 2 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2005 VL 567 BP 117 EP 147 PG 31 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BDN28 UT WOS:000234425900005 PM 16370138 ER PT S AU Che, MM Nie, ZZ Randazzo, PA AF Che, MM Nie, ZZ Randazzo, PA BE Balch, WE Der, CJ Hall, A TI Assays and properties of the Arf GAPs AGAP1, ASAP1, and Arf GAP1 SO GTPASES REGULATING MEMBRANE DYNAMICS SE Methods in Enzymology LA English DT Review; Book Chapter ID GTPASE-ACTIVATING PROTEIN; ADP-RIBOSYLATION FACTOR; PURIFICATION; FACTOR-1; IDENTIFICATION; PHOSPHOLIPIDS; CYTOSKELETON; EXPRESSION; CURVATURE; VESICLES AB ADP-ribosylation factors (Arfs) are Ras-like GTP-binding proteins that regulate membrane traffic and actin remodeling. Arf function requires GTP hydrolysis but Arf lacks GTPase activity; consequently, Arf function is dependent on Arf GTPase-activating proteins (GAPS). The Arf GAPS are a structurally diverse group of at least 16 proteins. Several Arf GAPS use a single Arf isoform. However, due to structural differences, the conditions supporting productive interactions between Arf and different Arf GAPS vary. Here, we describe preparation and basic properties of three Arf GAPS. We use these proteins to illustrate assays for Arf GAP activity. Conditions that optimize activity for each GAP are discussed. These methods can be used for the further characterization of Arf-Arf GAP interaction that is necessary for understanding the function of Arf in cellular physiology. C1 NCI, Cellular Oncol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Che, MM (reprint author), NCI, Cellular Oncol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NR 40 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182809-3 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 404 BP 147 EP 163 DI 10.1016/S0076-6879(05)04015-2 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDO67 UT WOS:000234565700015 PM 16413266 ER PT S AU Ha, VL Thomas, GMH Stauffer, S Randazzo, PA AF Ha, VL Thomas, GMH Stauffer, S Randazzo, PA BE Balch, WE Der, CJ Hall, A TI Preparation of myristoylated Arf1 and Arf6 SO GTPASES REGULATING MEMBRANE DYNAMICS SE Methods in Enzymology LA English DT Review; Book Chapter ID ADP-RIBOSYLATION FACTOR; NUCLEAR-MAGNETIC-RESONANCE; NUCLEOTIDE EXCHANGE FACTOR; GTP-BINDING PROTEIN; N-TERMINAL FRAGMENT; GOLGI MEMBRANES; PHOSPHOLIPASE-D; FACTOR-I; SACCHAROMYCES-CEREVISIAE; DOWNSTREAM EFFECTOR AB Arf proteins are members of the Arf family of small Ras-like GTP binding proteins. Six Arfs, grouped into three classes, have been identified in mammalian cells and three members have been identified in yeasts. Arf1 and Arf6, more extensively studied than other Arfs, have been found to affect membrane traffic and actin remodeling. A structural feature that distinguishes Arfs from other Ras superfamily members is an N-terminal alpha-helix, extending from the basic G-protein fold, which is cotranslationally myristoylated. Both the helix and the myristate affect biochemical properties of Arfs, including nucleotide exchange, membrane association, and interaction with some effector proteins. Preparation of myristoylated Arf for in vitro studies of Arf function requires consideration of both the reaction yielding myristoylated protein and the properties of the modified Arfs. Here, we describe methods that yield homogeneous preparations of myristoylated Arf1 and Arf6. C1 NCI, Cellular Oncol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Ha, VL (reprint author), NCI, Cellular Oncol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NR 42 TC 23 Z9 23 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182809-3 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 404 BP 164 EP 174 DI 10.1016/S0076-6879(05)04016-4 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDO67 UT WOS:000234565700016 PM 16413267 ER PT S AU Jones, HD Moss, J Vaughan, M AF Jones, HD Moss, J Vaughan, M BE Balch, WE Der, CJ Hall, A TI BIG1 and BIG2, brefeldin A-inhibited guanine nucleotide-exchange factors for ADP-ribosylation factors SO GTPASES REGULATING MEMBRANE DYNAMICS SE Methods in Enzymology LA English DT Review; Book Chapter ID SEC7 DOMAIN; PROTEIN; LOCALIZATION; COMPLEX; IDENTIFICATION; TRANSPORT; MEMBRANE; CONTAINS; CLONING AB BIG1 and BIG2 are large (similar to 200 kDa) guanine nucleotide-exchange proteins for ADP-ribosylation factors, or ARFs, that were isolated based on sensitivity of their guanine nucleotide-exchange activity to inhibition by brefeldin A. The intracellular distributions of BIG1 and BIG2 differ from those of other ARF guanine nucleotide-exchange proteins. In addition to its presence in Golgi membranes, BIG2 is seen in peripheral vesicular structures that most likely represent recycling endosomes, and BIG1 is found in nuclei of serum-starved HepG2 cells. Several binding partners for BIG1 and BIG2 that were identified via yeast two-hybrid screens include FKBP13 and myosin IXb for BIG1 and, for BIG2, the regulatory RI alpha subunit of protein kinase A, Exo70, and the GABA receptor beta subunit. Autosomal recessive periventricular heterotopia with microcephaly, a disorder of human embryonic development due to defective vesicular trafficking, has been attributed to mutations in BIG2. Methods for purification of BIG1 and BIG2 from HepG2 cells are presented here, along with a summary of information regarding their structure and function. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Jones, HD (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 29 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182809-3 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 404 BP 174 EP 184 DI 10.1016/S0076-6879(05)04017-6 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDO67 UT WOS:000234565700017 PM 16413268 ER PT S AU Pacheco-Rodriguez, G Moss, J Vaughan, M AF Pacheco-Rodriguez, G Moss, J Vaughan, M BE Balch, WE Der, CJ Hall, A TI Cytohesin-1: Structure, function, and ARF activation SO GTPASES REGULATING MEMBRANE DYNAMICS SE Methods in Enzymology LA English DT Review; Book Chapter ID GUANINE-NUCLEOTIDE-EXCHANGE; ADP-RIBOSYLATION FACTORS; FACTOR SEC7 DOMAIN; BREFELDIN-A; PH DOMAIN; PLASMA-MEMBRANE; FACTOR ARNO; PROTEIN; BINDING; GENE AB Mammalian cytohesins are a family of very similar guanine nucleotide-exchange proteins (GEPs) that activate ADP-ribosylation factors (ARFs). Cytohesins are multifunctional molecules comprising a Sec? domain that is responsible for the GEP activity, a PH domain that binds specific phosphatidylinositol phosphates, and a coiled-coil domain responsible for homodimerization and interaction with other proteins. Cytohesin proteins are ubiquitous and have been implicated in several functions including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. Unlike the GEP activity of BIG1 and BIG2, the acceleration by cytohesins of guanine nucleotide exchange to generate active ARF-GTP is not inhibited by the fungal metabolite brefeldin, A (BFA). This chapter is concerned for the most part with cytohesin-1 and the assay of its GEP activity. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Pacheco-Rodriguez, G (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 48 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182809-3 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 404 BP 184 EP 195 DI 10.1016/S0076-6879(05)04018-8 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDO67 UT WOS:000234565700018 PM 16413269 ER PT S AU Vichi, A Moss, J Vaughan, M AF Vichi, A Moss, J Vaughan, M BE Balch, WE Der, CJ Hall, A TI ADP-ribosylation factor domain protein 1 (ARD1), a multifunctional protein with ubiquitin E3 ligase, GAP, and ARF domains SO GTPASES REGULATING MEMBRANE DYNAMICS SE Methods in Enzymology LA English DT Review; Book Chapter ID GTPASE-ACTIVATING DOMAIN; CHOLERA-TOXIN; BINDING-PROTEIN; RING; PURIFICATION; IDENTIFICATION; LOCALIZATION; COFACTOR; FAMILY; REGION AB ADP-ribosylation factor domain protein 1 (ARD1) is a multifunctional protein that belongs to the family of 20-kDa ARF proteins. The ARD1 gene encodes a 64-kDa protein with a structure comprising an 18-kDa ADP-ribosylation factor (ARF) domain at the C-terminus (amino acids 403-574), and a 46-kDa N-terminal domain (amino acids 1-402) that contains, from the translation start site, a RING finger domain, two predicted B-Boxes, and a coiled-coil protein interaction motif, which places it among the TRIM (tripartite motif) or RBCC (RING, B-Box, coiled-coil) protein families. Recombinant ARD1 (amino acids 1-574) or its RING finger domain (amino acids 1-110) produced polyubiquitylated proteins when incubated in vitro with a mammalian El, an E2 enzyme (UbcH6 or UbeH5a, -5b, or -5c), ATP, and ubiquitin. Via its C-terminal ARF domain, recombinant ARD1 binds guanine nucleotides, through which it can enhance, in a GTP-dependent manner, cholera toxin ADP-ribosyltransferase activity. Unlike ARFs, ARD1, but not its ARF domain, exhibits significant GTPase activity. Hydrolysis of GTP bound to the C-terminal ARF domain was stimulated by addition of the 46-kDa N-terminal domain (amino acids 1-402) via its GTPase activating protein (GAP) activity. The rate of GDP dissociation from the C-terminal ARE domain in ARD1, is slowed by the adjacent 15 amino acids, which act as a GDP-dissociation inhibitor (GDI) domain. Cytohesin-1, known already as a guanine nucleotide-exchange factor (GEF) ARF activator, also specifically activated recombinant human ARD1, via activation of the ARF domain. Overexpressed ARD1 fusion proteins were associated with structures resembling lysosomes and Golgi membranes, as well as the nucleus, in different types of cells, and sequences potentially responsible for the intracellular localizations were identified. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 30 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182809-3 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 404 BP 195 EP 206 DI 10.1016/S0076-6879(05)04019-X PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDO67 UT WOS:000234565700019 PM 16413270 ER PT S AU Yoon, HY Bonifacino, JS Randazzo, PA AF Yoon, HY Bonifacino, JS Randazzo, PA BE Balch, WE Der, CJ Hall, A TI In vitro assays of Arf1 interaction with GGA proteins SO GTPASES REGULATING MEMBRANE DYNAMICS SE Methods in Enzymology LA English DT Review; Book Chapter ID TRANS-GOLGI NETWORK; MANNOSE 6-PHOSPHATE RECEPTORS; GTPASE-ACTIVATING PROTEINS; ADAPTIN EAR DOMAIN; GAMMA-ADAPTIN; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; GAT DOMAIN; MEMBRANE-TRANSPORT; UBIQUITIN BINDING AB ADP-ribosylation factor 1 (Arf1) is a GTP-binding protein that regulates membrane traffic. This function of Arf1 is, at least in part, mediated by Arf1(.)GTP binding to coat proteins such as coatomer, clathrin adaptor protein (AP) complexes 1 and 3, and gamma-adaptin homology-Golgi associated Arf-binding (GGA) proteins. Binding to Arf1(.)GTP recruits these coat proteins to membranes, leading to the formation of transport vesicles. Whereas coatomer and the AP complexes are hetero-oligomers, GGAs are single polypeptide chains. Therefore, working with recombinant GGAs is straightforward compared to the other Arf1 effectors. Consequently, the GGAs have been used as a model for studying Arf1 interactions with effectors and as reagents to determine Arf1(.)GTP levels in cells. In this chapter, we describe in vitro assays for analysis of GGA interaction with Arf1.GTP and for determining intracellular Arf1(.)GTP levels. C1 NCI, Cellular Oncol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Yoon, HY (reprint author), NCI, Cellular Oncol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 48 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182809-3 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 404 BP 316 EP 332 DI 10.1016/S0076-6879(05)04028-0 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDO67 UT WOS:000234565700028 PM 16413279 ER PT S AU Welch, AY Riley, KN D'Souza-Schorey, C Herman, IM AF Welch, AY Riley, KN D'Souza-Schorey, C Herman, IM BE Balch, WE Der, CJ Hall, A TI Arf6 modulates the beta-actin specific capping protein, beta cap73 SO GTPASES REGULATING MEMBRANE DYNAMICS SE Methods in Enzymology LA English DT Review; Book Chapter ID RHO GTPASES; CELL-SHAPE; HEAVY-MEROMYOSIN; IN-VITRO; F-ACTIN; MOTILITY; MUSCLE; INJURY; CONTRACTILE; BINDING AB Recent work from our laboratory has revealed that isoactin cytoskeletal and membrane dynamics are coordinately regulated. In this chapter, we review some of the recent and relevant scientific literature focusing on key aspects of cytoskeletal and membrane-mediated signal transduction. Additionally, we highlight some of the strategic molecular, biochemical, and cell-based methodologies that we have either developed or implemented in our efforts aimed at revealing the pivotal role(s) that the actin isoforms play in controlling cell shape and motility during developmental and/or disease-associated events. Furthermore, we address the central position of beta-actin and its barbed end-specific capping protein, beta cap73, in modulating nonmuscle cell membrane dynamics and cell migration. In studying the molecular mechanisms mediating these cytoskeletal protein interactions, we have recently recognized that cell motility and beta-actin dynamics are controlled by the direct association of beta cap73 with the plasma membrane- and endosome-associated protein, ADP-ribosylation factor 6 (Arf6). C1 Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. NIAID, NIH, Off Technol Dev, Bethesda, MD 20892 USA. RP Herman, IM (reprint author), Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. EM ira.herman@tufts.edu NR 28 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182809-3 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 404 BP 377 EP 387 DI 10.1016/S0076-6879(05)04033-4 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDO67 UT WOS:000234565700033 PM 16413284 ER PT S AU Weigert, R Donaldson, JG AF Weigert, R Donaldson, JG BE Balch, WE Der, CJ Hall, A TI Fluorescent microscopy-based assays to study the role of Rab22a in clathrin-independent endocytosis SO GTPASES REGULATING MEMBRANE TARGETING AND FUSION SE Methods in Enzymology LA English DT Review; Book Chapter ID PROTEINS; PATHWAY; RAB11; ARF6 AB The endocytic and trafficking route followed by proteins that enter cells independently of clathrin is not well understood. In HeLa cells, a distinct endocytic and recycling pathway is followed for such clathrin-independent cargo proteins, and we have characterized the role of Rab proteins in this process. Here we describe cell-based flourescence assays to examine the effects of expression and depletion of Rab22 on endosomal morphology and endocytic recycling. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Weigert, R (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 12 TC 9 Z9 9 U1 3 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182808-5 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 403 BP 243 EP 253 DI 10.1016/S0076-6879(05)03020-X PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDQ05 UT WOS:000234855400020 PM 16473591 ER PT S AU Hierro, A Kim, JW Hurley, JH AF Hierro, A Kim, JW Hurley, JH BE Balch, WE Der, CJ Hall, A TI Polycistronic expression and purification of the ESCRT-II endosomal trafficking complex SO GTPASES REGULATING MEMBRANE TARGETING AND FUSION SE Methods in Enzymology LA English DT Review; Book Chapter ID MULTIVESICULAR BODIES; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; UBIQUITIN LIGASE; PROTEINS; COMPARTMENT; MACHINERY; LYSOSOMES; REQUIRES; PATHWAY AB Eukaryotic cells use sophisticated mechanisms to direct protein traffic between subcellular compartments. In eukaryotic cells, transmembrane proteins are delivered for degradation in the lysosome or yeast vacuole via multivesicular bodies. The sorting of proteins into lumenal vesicles within multivesicular bodies is directed by the three ESCRT protein complexes. Here we describe the expression and purification of the ESCRT-II complex using the polycistronic expression vector pST39 developed by Tan. In a modification of Tan's procedure, Pfu polymerase amplification with overlapping oligonucleotides was used to generate the translation cassettes for subcloning into pST39 expression vector in a single step. This approach reduces the number of restriction sites and subcloning steps required to express a heterooligomeric protein complex, facilitating rapid screening of multiple complexes and complex variants for crystallization or biochemical characterization. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hierro, A (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI Hierro, Aitor/F-9998-2011 OI Hierro, Aitor/0000-0002-7721-1581 NR 35 TC 6 Z9 8 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182808-5 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 403 BP 322 EP 332 DI 10.1016/S0076-6879(05)03027-2 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDQ05 UT WOS:000234855400027 PM 16473598 ER PT J AU Aggarwal, A Grewal, R Green, RJ Boggio, L Green, D Weksler, BB Wiestner, A Schechter, GP AF Aggarwal, A Grewal, R Green, RJ Boggio, L Green, D Weksler, BB Wiestner, A Schechter, GP TI Rituximab for autoimmune haemophilia: a proposed treatment algorithm SO HAEMOPHILIA LA English DT Article DE autoimmune hemophilia; rituximab; factor VIII inhibitors ID FACTOR-VIII INHIBITORS; CHRONIC LYMPHOCYTIC-LEUKEMIA; RECOMBINANT FACTOR VIIA; PORCINE FACTOR-VIII; ACQUIRED HEMOPHILIA; IMMUNOSUPPRESSIVE THERAPY; GAMMA-GLOBULIN; IN-VIVO; CYCLOSPORINE; CONCENTRATE AB We previously reported durable complete responses following brief courses of rituximab and prednisone with or without cyclophosphamide in four patients with autoimmune haemophilia and inhibitor titres of 5-60 BU. We report here responses to this monoclonal anti-CD20 antibody in four additional patients, including two patients with inhibitor titres >200 BU. Factor VIII levels became normal 2-35weeks after 4 or 8 weekly doses of rituximab, brief courses of prednisone and in one patient immunoglobulin. Complete responses are ongoing at 10 months in two patients. Two patients relapsed: a patient whose initial inhibitor titre was 525 BU relapsed at 3.5 months and a long-term prednisone-dependent patient at 8.5 months. Both responded to second courses of rituximab and prednisone and are in remission. Our experience suggests that rituximab is a safe and effective addition to immunosuppression with prednisone and cyclophosphamide to treat autoimmune haemophilia, and may permit early discontinuation or even avoidance of these potentially toxic agents. High-titre inhibitor patients, however, may require multiple courses of rituximab or the addition of cyclophosphamide. Pending randomized studies, we propose an algorithm based on our experience and other reports for incorporating rituximab in the treatment of this rare disorder. C1 Washington Hosp Ctr, Washington, DC 20010 USA. Palm Beach Canc Inst, W Palm Beach, FL USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Cornell Univ, Weill Med Coll, New York, NY USA. NCI, NIH, Bethesda, MD 20892 USA. VA Med Ctr, Washington, DC USA. George Washington Univ, Washington, DC USA. RP Aggarwal, A (reprint author), Washington Hosp Ctr, Washington, DC 20010 USA. EM anita.aggarwal@medstar.net NR 33 TC 67 Z9 70 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD JAN PY 2005 VL 11 IS 1 BP 13 EP 19 DI 10.1111/j.1365-2516.2005.01060.x PG 7 WC Hematology SC Hematology GA 890DH UT WOS:000226491400004 PM 15660983 ER PT J AU Kersten, M Kulik, DA Dainty, JR Fox, TE Byczkowski, JZ Bal, W Kasprzak, K AF Kersten, Michael Kulik, Dmitrii A. Dainty, Jack R. Fox, Tom E. Byczkowski, Janusz Z. Bal, Wojciech Kasprzak, Kazimierz BE Cornelis, R TI Modeling of Elemental Species SO HANDBOOK OF ELEMENTAL SPECIATION II: SPECIES IN THE ENVIRONMENT, FOOD, MEDICINE AND OCCUPATIONAL HEALTH LA English DT Article; Book Chapter ID GIBBS ENERGY MINIMIZATION; PLASMA-MASS SPECTROMETRY; PERFORMANCE LIQUID-CHROMATOGRAPHY; WASTE STABILIZATION SYSTEMS; AQUEOUS SOLUBILITY DIAGRAMS; PHYSIOLOGICALLY-BASED MODEL; CALCIUM SILICATE HYDRATE; STABLE-ISOTOPE TRACERS; N-TERMINAL SEQUENCE; HUMAN PROTAMINE HP2 C1 [Kersten, Michael] Johannes Gutenberg Univ Mainz, Mainz, Germany. [Kulik, Dmitrii A.] Paul Scherrer Inst, Villigen, Switzerland. [Dainty, Jack R.; Fox, Tom E.] AFRC, Inst Food Res, Norwich NR4 7UA, Norfolk, England. [Byczkowski, Janusz Z.] JZB Consulting, Fairborn, OH USA. [Bal, Wojciech] Polish Acad Sci, Inst Biochem & Biophys, Warsaw, Poland. [Kasprzak, Kazimierz] NCI, Frederick, MD 21701 USA. RP Kersten, M (reprint author), Johannes Gutenberg Univ Mainz, Mainz, Germany. NR 342 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-85600-0 PY 2005 BP 651 EP 736 DI 10.1002/0470856009.ch3a D2 10.1002/0470856009 PG 86 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA BYC07 UT WOS:000297859900004 ER PT J AU Waters, M Boorman, G Bushel, P Cunningham, M Irwin, R Merrick, A Olden, K Paules, R Selkirk, J Stasiewicz, S Weis, B Van Houten, B Walker, N Wan, HH Tennant, R AF Waters, Michael Boorman, Gary Bushel, Pierre Cunningham, Michael Irwin, Rick Merrick, Alex Olden, Kenneth Paules, Richard Selkirk, James Stasiewicz, Stanley Weis, Brenda Van Houten, Ben Walker, Nigel Wan, Honghui Tennant, Raymond BE Borlak, J TI The Chemical Effects in Biological Systems (CEBS) Knowledge Base SO HANDBOOK OF TOXICOGENOMICS: STRATEGIES AND APPLICATIONS LA English DT Article; Book Chapter ID GENE-EXPRESSION REGULATION; MOLECULAR CLASSIFICATION; MICROARRAY TECHNOLOGY; TRANSCRIPTION FACTORS; METABOLIC-RESPONSES; DRUG DISCOVERY; MOUSE-LIVER; TOXICOGENOMICS; TOXICITY; TOXICOLOGY C1 [Waters, Michael; Boorman, Gary; Bushel, Pierre; Cunningham, Michael; Irwin, Rick; Merrick, Alex; Olden, Kenneth; Paules, Richard; Selkirk, James; Stasiewicz, Stanley; Weis, Brenda; Van Houten, Ben; Walker, Nigel; Tennant, Raymond] NIEHS, Res Triangle Pk, NC 27709 USA. RP Waters, M (reprint author), NIEHS, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 70 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-3-527-60371-8 PY 2005 BP 201 EP 232 DI 10.1002/3527603719.ch10 D2 10.1002/3527603719 PG 32 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA BYE04 UT WOS:000298178300012 ER PT J AU Selkirk, JK Waters, MD Tennant, RW AF Selkirk, James K. Waters, Michael D. Tennant, Raymond W. BE Borlak, J TI The National Toxicogenomics Program SO HANDBOOK OF TOXICOGENOMICS: STRATEGIES AND APPLICATIONS LA English DT Article; Book Chapter ID GENE-EXPRESSION; RISK-ASSESSMENT; DRUG DISCOVERY; CANCER-RISK; TOXICOLOGY; TECHNOLOGIES; ARRAYS; CELLS; GUIDELINES; TUMOR C1 [Selkirk, James K.; Waters, Michael D.; Tennant, Raymond W.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Selkirk, JK (reprint author), NIEHS, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 38 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-3-527-60371-8 PY 2005 BP 611 EP 621 D2 10.1002/3527603719 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA BYE04 UT WOS:000298178300027 ER PT J AU Resnik, DB AF Resnik, DB TI Conflicts of interest at the NIH: No easy solution SO HASTINGS CENTER REPORT LA English DT Article ID FINANCIAL CONFLICTS; BIOMEDICAL-RESEARCH C1 NIEHS, NIH, Res Triangle Pk, NC USA. RP Resnik, DB (reprint author), NIEHS, NIH, Res Triangle Pk, NC USA. NR 16 TC 2 Z9 2 U1 0 U2 4 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD JAN-FEB PY 2005 VL 35 IS 1 BP 18 EP 20 PG 3 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 902YK UT WOS:000227392400019 PM 15799496 ER PT J AU Jamison, DT Lau, LJ Wang, J AF Jamison, Dean T. Lau, Lawrence J. Wang, Jia BE LopezCasasnovas, G Rivera, B Currais, L TI Health's Contribution to Economic Growth in an Environment of Partially Endogenous Technical Progress SO HEALTH AND ECONOMIC GROWTH: FINDINGS AND POLICY IMPLICATIONS LA English DT Article; Book Chapter ID PANEL-DATA APPROACH; BASIC NEEDS; COUNTRIES; EMPIRICS; CONVERGENCE; POLICIES; MALARIA; MODEL C1 [Jamison, Dean T.] Univ Calif Los Angeles, Fogarty Int Ctr, NIH, Los Angeles, CA 90024 USA. [Jamison, Dean T.] World Bank, Res Dept, Washington, DC USA. [Lau, Lawrence J.] Stanford Univ, Dept Econ, Stanford, CA 94305 USA. [Lau, Lawrence J.] Acad Sinica, Taipei, Taiwan. [Wang, Jia] Univ Calif Los Angeles, Ctr Study Evaluat, Los Angeles, CA 90024 USA. NR 59 TC 30 Z9 31 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-262-25260-7 PY 2005 BP 67 EP 91 PG 25 WC Economics; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA BPT24 UT WOS:000279843700005 ER PT S AU Dunbar, CE AF Dunbar, CE BE Kanz, L Weisel, KC Orlic, D Fibbe, WE TI Insights into integration and hematopoiesis from primate genetic marking studies SO HEMATOPOIETIC STEM CELLS V SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th International Conference on Hematopoietic Stem Cells CY SEP 16-18, 2004 CL Univ Tubingen, Tubingen, GERMANY HO Univ Tubingen DE nonhuman primates; hematopoietic stem cells; murine leukemia virus; simian immunodeficiency virus ID RETROVIRAL TRANSDUCTION; NONHUMAN-PRIMATES; CELLS; STEM; ENGRAFTMENT; PROGENITOR; MODEL AB Genetic marking strategies in the nonhuman primate model have elucidated a number of principles with relevance to implementation of clinical stem cell therapies, including the lineage potential, number, and life span of hematopoietic stem and progenitor cells. The recent occurrence of leukemias likely related to insertional activation of a proto-oncogene in two patients with X-severe combined immunodeficiency (SCID) syndromes treated with CD34(+) cells transduced with retroviral vectors expressing the corrective common gamma cytokine receptor gene has refocused attention on the issue of retroviral integration. We have analyzed > 1500 independent insertions from rhesus macaques transplanted with CD34(+) cells transduced with either MLV or SIV vectors. Of these, 46 rhesus macaques followed long term have not had progression to leukemia, abnormal hematopoiesis, or clonal hematopoiesis. However, the pattern of both MLV and SIV integrants in cells of these animals was found to be highly nonrandom, with a propensity for insertions of both vectors within genes: for MLV particularly near the transcription start site, and for SIV particularly in gene-dense regions. C1 NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Dunbar, CE (reprint author), NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, 10 Ctr Dr,Bldg 10 CRC,Room 4E-5132, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov NR 9 TC 12 Z9 12 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-588-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1044 BP 178 EP 182 DI 10.1196/annals.1349.023 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Science & Technology - Other Topics GA BCR23 UT WOS:000230894100021 PM 15958711 ER PT J AU Feld, JJ Liang, TJ AF Feld, JJ Liang, TJ TI HCV persistence: Cure is still a four letter word SO HEPATOLOGY LA English DT Editorial Material ID CHRONIC HEPATITIS-C; B-VIRUS-INFECTION; POLYMERASE-CHAIN-REACTION; INTERFERON-ALPHA; HIGH PREVALENCE; LIVER-DISEASE; RNA SEQUENCES; DRUG-USERS; RIBAVIRIN; THERAPY C1 NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Feld, JJ (reprint author), NIDDK, Liver Dis Branch, NIH, 10 Ctr Dr,Rm 9B16,MSC 1800, Bethesda, MD 20892 USA. EM feldj@niddk.nih.gov NR 23 TC 21 Z9 22 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2005 VL 41 IS 1 BP 23 EP 25 DI 10.1002/hep.20561 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 886RC UT WOS:000226245000005 PM 15690477 ER PT J AU Toyooka, N Kawasaki, M Nemoto, H Daly, JW Spande, TF Garraffo, HM AF Toyooka, N Kawasaki, M Nemoto, H Daly, JW Spande, TF Garraffo, HM TI Enantioselective synthesis of poison-frog alkaloid 237D and determination of absolute stereochemistry SO HETEROCYCLES LA English DT Article ID INDOLIZIDINE AB An enantioselective synthesis of the 5-heptyl-8-methylindolizidine ((-)7) has been achieved. Alkaloid ((-)-7, (MW 237)) was used to determine the relative and absolute stereochemistry of the natural indolizidine 237D from frog skin as 5S, 8S, 9R using GC-IR and GC-MS. Chiral gas-chromatographic comparisons with catalytically reduced (+)-235B" and (-)-235B' indicated (-)-7 had the same absolute stereochemistry as the dihydro-product resulting from (-)-23513' and is naturally occurring in certain extracts of Panamanian poison frogs (Dendrobates). C1 Toyama Med & Pharmaceut Univ, Fac Pharmaceut Sci, Toyama 9300194, Japan. Toyama Prefectural Univ, Fac Engn, Dept Liberal Arts & Sci, Toyama 9390398, Japan. NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Toyooka, N (reprint author), Toyama Med & Pharmaceut Univ, Fac Pharmaceut Sci, Sugitani 2630, Toyama 9300194, Japan. NR 7 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD JAN 1 PY 2005 VL 65 IS 1 BP 5 EP 8 PG 4 WC Chemistry, Organic SC Chemistry GA 897VB UT WOS:000227032400002 ER PT S AU Simon, SL AF Simon, SL BE Sugahara, T Morishima, H Sohrabi, M Sasaki, Y Hayata, I Akiba, S TI Dosimetric considerations for environmental radiation and NORM SO HIGH LEVELS OF NATURAL RADIATION AND RADON AREAS: RADIATION DOSE AND HEALTH EFFECTS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 6th International Conference on High Levels of Natural Radiation and Radon Areas CY SEP 06-10, 2004 CL Kinki Univ, Osaka, JAPAN SP Hlth Res Fdn, Japan Vasc Dis Res Fdn, Japan Nucl Cycle Dev Inst, Commemorat Org Japan World Exposit 70, Inoue Fdn Sci, Kao Fdn Arts & Sci, Osaka Convent & Tourism Bur, Chiyoda Technol Corp, Kansai Elect Power Co, Tokyo Elect Power Co, Pony Ind Co Ltd, Fuji elect Syst Co Ltd, Aloka Co Ltd, Nagase Landauer Ltd HO Kinki Univ DE dose; dosimetry; natural background radiation; NORM; epidemiology AB The physical theory of dosimetry for environmental radiation, including radiation emitted from naturally occurring radioactive materials (NORM), is no different than that required in any other setting where doses are estimated. However, the application of such theory to environmental radiation and NORM may require considerations that differ from dose estimation elsewhere. This is especially true if the intent is to provide estimated doses for epidemiologic analyses. It should be realized that metrics of radiation dose for radiation protection purposes are generally not the same as for analytic epidermologic studies which require estimates of absorbed dose to specific organs of identified persons. In addition, exposures to environmental radiation and NORM typically involve radiation fields that vary considerably over space, and the patterns of an individual's movements, as well as the types of buildings in which they reside and work, can significantly affect the dose received from external radiation. Realistically describing the spatial variation of environmental exposure rates is a difficult challenge for environmental dosimetry, rather than the physical principles that are relatively well understood. This publication will review these ideas in the context of improving estimated doses from high background radiation studies. (c) 2004 Elsevier B.V. All rights reserved. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov NR 4 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 0-444-51431-7 J9 INT CONGR SER PY 2005 VL 1276 BP 89 EP 92 DI 10.1016/j.ics.2004.11.016 PG 4 WC Biophysics; Public, Environmental & Occupational Health; Multidisciplinary Sciences SC Biophysics; Public, Environmental & Occupational Health; Science & Technology - Other Topics GA BCM59 UT WOS:000230000900021 ER PT J AU McNamara, RK Hussain, RJ Simon, EJ Stumpo, DJ Blackshear, PJ Abel, T Lenox, RH AF McNamara, RK Hussain, RJ Simon, EJ Stumpo, DJ Blackshear, PJ Abel, T Lenox, RH TI Effect of myristoylated alanine-rich C kinase substrate (MARCKS) overexpression on hippocampus-dependent learning and hippocampal synaptic plasticity in MARCKS transgenic mice SO HIPPOCAMPUS LA English DT Article DE MARCKS; transgenic mice; protein kinase C; hippocampus; paired-pulse facilitation; long-term potentiation; fear conditioning; Morris water maze ID LONG-TERM POTENTIATION; DBA/2 MICE; RAT-BRAIN; CONTEXTUAL FEAR; ACTIN-FILAMENT; PROTEIN; EXPRESSION; PHOSPHORYLATION; C57BL/6; CALMODULIN AB The myristoylated alanine-rich C kinase substrate (MARCKS) is a primary substrate of protein kinase C (PKC) thought to regulate membrane-filamentous actin cytoskeletal plasticity in response to PKC activity in the regulation of synaptic efficacy. We have recently reported that MARCKS expression is significantly elevated (45%) in the hippocampus of DBA/2J mice, which exhibit impaired hippocampus-dependent learning and hippocampal long-term potentiation (LTP), compared with C57BL/6J mice. The latter finding led us to hypothesize that elevations in MARCKS expression are detrimental to hippocampal plasticity and function. To assess this more directly, we examined hippocampal (CA1) paired-pulse facilitation and LTP, and hippocampus-dependent learning in mice overexpressing MARCKS through the expression of a human MARCKS transgene (Tg(+)). The human MARCKS protein was confirmed to be expressed in the hippocampus of Tg(+) mice but not in Tg(-) mice. Schaffer collateral paired-pulse facilitation, input-output responses, and LTP did not differ between Tg+ and Tg(-) mice, indicating that neurotransmitter release, short-term, and long-term synaptic plasticity are not impaired by MARCKS overexpression. In the Morris water maze, Tg(+) mice exhibited a mild but significant spatial learning impairment during initial acquisition, and a more severe impairment during reversal training. Tg(+) did not exhibit impaired swim speed or visible platform performance relative to Tg(-) mice, indicating the absence of gross sensorimotor deficits. Fear conditioning to either context or cue was not impaired in Tg(+) mice. Behavioral deficits could not be attributed to differences in hippocampal PKC isozyme (alpha, beta(II), gamma, epsilon, zeta) or calmodulin expression, or alterations in hippocampal cytoarchitecture or infrapyramidal mossy fiber limb length. Collectively, these results indicate that elevations in MARCKS expression are detrimental to specific aspects of hippocampal function. (c) 2005 Wiley-Liss, Inc. C1 Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. RP McNamara, RK (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat, 231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM robert.mcnamara@psychiatry.uc.edu RI McNamara, Robert/J-4309-2014 FU NIA NIH HHS [R01 AG18199]; NICHD NIH HHS [HD26979]; NIMH NIH HHS [R01 MH59959, R01 MH60244] NR 46 TC 22 Z9 23 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2005 VL 15 IS 5 BP 675 EP 683 DI 10.1002/hipo.20089 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 946DU UT WOS:000230553300012 PM 15889447 ER PT J AU Olariu, A Cleaver, KM Shore, LE Brewer, MD Cameron, HA AF Olariu, A Cleaver, KM Shore, LE Brewer, MD Cameron, HA TI A natural form of learning can increase and decrease the survival of new neurons in the dentate gyrus SO HIPPOCAMPUS LA English DT Article DE hippocampus; adult neurogenesis; granule cell; learning; memory; cell death ID GRANULE CELL DEGENERATION; RATS RATTUS-NORVEGICUS; ODOR-ODOR ASSOCIATION; LONG-TERM-MEMORY; ADULT NEUROGENESIS; HIPPOCAMPAL REGION; TOPOGRAPHIC ORGANIZATION; SYNAPTIC PLASTICITY; DEPENDENT MECHANISM; RETROGRADE-AMNESIA AB Granule cells born in the adult dentate gyrus undergo a 4-week developmental period characterized by high susceptibility to cell death. Two forms of hippocampus-dependent learning have been shown to rescue many of the new neurons during this critical period. Here, we show that a natural form of associative learning, social transmission of food preference (STFP), can either increase or decrease the survival of young granule cells in adult rats. Increased numbers of pyknotic as well as phospho-Akt-expressing BrdU-labeled cells were seen 1 day after STFP training, indicating that training rapidly induces both cell death and active suppression of cell death in different subsets. A single day of training for STFP increased the survival of 8-day-old BrdU-labeled cells when examined 1 week later. In contrast, 2 days of training decreased the survival of BrdU-Iabeled cells and the density of immature neurons, identified with crmp-4. This change from increased to decreased survival could not be accounted for by the ages of the cells. Instead, we propose that training may initially increase young granule cell survival, then, if continued, cause them to die. This complex regulation of cell death could potentially serve to maintain granule cells that are actively involved in memory consolidation, while rapidly using and discarding young granule cells whose training is complete to make space for new naive neurons. Published 2005 Wiley-Liss, Inc. C1 NIMH, NIH, Unit Neuroplast, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Cameron, HA (reprint author), NIMH, NIH, Unit Neuroplast, Dept Hlth & Human Serv, Bldg 35-3C915,MSC 3718,35 Lincoln Dr, Bethesda, MD 20892 USA. EM heathercameron@mail.nih.gov RI Cameron, Heather/E-6221-2011; OI Cameron, Heather/0000-0002-3245-5777; prescott, lauren/0000-0002-1006-8645 NR 60 TC 51 Z9 53 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2005 VL 15 IS 6 BP 750 EP 762 DI 10.1002/hipo.20097 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 952TC UT WOS:000231027400007 PM 16010660 ER PT J AU Wei, L Shi, YB AF Wei, L Shi, YB TI Matrix metalloproteinase stromelysin-3 in development and pathogenesis SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Review DE matrix metalloproteinase; stromelysin-3; metamorphosis; Xenopus laevis; tumor invasion; metastasis ID IMPLICATES DISTINCT FUNCTIONS; THYROID-HORMONE REGULATION; XENOPUS-LAEVIS; EXTRACELLULAR-MATRIX; BREAST-CARCINOMA; CONNECTIVE-TISSUE; GENE-EXPRESSION; IV COLLAGENASE; PULMONARY CARCINOMAS; RECEPTOR SUPERFAMILY AB The extracellular matrix (ECM) serves as a medium for cell-cell interactions and can directly signal cells through cell surface ECM receptors, such as integrins. In addition, many growth factors and signaling molecules are stored in the ECM. Thus, ECM remodeling and/or degradation plays a critical role in cell fate and behavior during many developmental and pathological processes. ECM remodeling/degradation is, to a large extent, mediated by matrix metalloproteinases (MMPs), a family of extracellular or membrane-bound, Zn2+-dependent proteases that are capable of digesting various proteinaceous components of the ECM. Of particular interest among them is the MMP11 or stromelysin-3, which was first isolated as a breast cancer associated protease. Here, we review some evidence for the involvement of this MMP in development and diseases with a special emphasis on amphibian metamorphosis, a postembryonic, thyroid hormone-dependent process that transforms essentially every organ/tissue of the animal. C1 NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), NICHD, Lab Gene Regulat & Dev, NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. EM shi@helix.nih.gov NR 99 TC 20 Z9 20 U1 0 U2 0 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 2005 VL 20 IS 1 BP 177 EP 185 PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 882VX UT WOS:000225968900021 PM 15578436 ER PT J AU Henke, RT Maitra, A Paik, S Wellstein, A AF Henke, RT Maitra, A Paik, S Wellstein, A TI Gene expression analysis in sections and tissue microarrays of archival tissues by mRNA in situ hybridization SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Review DE mRNA; In situ ybridization; tissue microarray; expression analysis ID FACTOR-BINDING-PROTEIN; LASER CAPTURE MICRODISSECTION; ANAPLASTIC LYMPHOMA KINASE; GROWTH-FACTOR PLEIOTROPHIN; COACTIVATOR AIB1; BREAST-CANCER; UP-REGULATION; OVEREXPRESSION; CARCINOGENESIS; TECHNOLOGY AB Altered expression of genes in diseased tissues can prognosticate a distinct natural progression of the disease as well as predict sensitivity or resistance to particular therapies. Archival tissues from patients with a known medical history and treatments are an invaluable resource to validate the utility of candidate genes for prognosis and prediction of therapy outcomes. However, stored tissues with associated long-term follow-up information typically are formalin-fixed, paraffin-embedded specimen and this can severely restrict the methods applicable for gene expression analysis. We report here on the utility of tissue microarrays (TMAs) that use valuable tissues sparingly and provide a platform for simultaneous analysis of gene expression in several hundred samples. In particular, we describe a stable method applicable to mRNA expression screening in such archival tissues. TMAs are constructed from sections of small drill cores, taken from tissue blocks of archival tissues and multiple samples can thus be arranged on a single microscope slide. We used mRNA in situ hybridization (ISH) on >500 full sections and >100 TMAs for >10 different cDNAs that yielded >10,000 data points. We provide detailed experimental protocols that can be implemented without major hurdles in a molecular pathology laboratory and discuss quantitative analysis and the advantages and limitations of ISH. We conclude that gene expression analysis in archival tissues by ISH is reliable and particularly useful when no protein detection methods are available for a candidate gene. C1 Georgetown Univ, Lombardi Canc Ctr, Washington, DC 20057 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD USA. Natl Surg Adjuvant Breast & Bowel Project, Div Pathol, Pittsburgh, PA USA. RP Wellstein, A (reprint author), Georgetown Univ, Lombardi Canc Ctr, Res Bldg E311,3970 Reservoir Rd NW, Washington, DC 20057 USA. EM wellstea@georgetown.edu OI Wellstein, Anton/0000-0002-0570-4950 NR 32 TC 6 Z9 6 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 2005 VL 20 IS 1 BP 225 EP 237 PG 13 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 882VX UT WOS:000225968900026 PM 15578441 ER PT J AU Cizza, G Romagni, P Lotsikas, A Lam, G Rosenthal, NE Chrousos, GP AF Cizza, G Romagni, P Lotsikas, A Lam, G Rosenthal, NE Chrousos, GP TI Plasma leptin in men and women with seasonal affective disorder and in healthy matched controls SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE major depression; leptin resistance; adipose tissue; body mass index; chronobiology; appetite score ID HUMANS; GENDER AB Seasonal affective disorder (SAD) is a specific clinical entity characterized by recurrent episodes of depression, which typically occur during the winter with periods of remission during the spring and summer. These depression episodes are accompanied by hyperphagia with cravings for carbohydrates and moderate weight gain, and usually respond to light therapy. We examined potential relationships between leptin, a hormone known to affect appetite and weight regulation, and seasonal changes in mood and appetite by measuring plasma leptin, clinical severity of depression, appetite scores, and body mass index (BMI) in 19 women and 8 men with SAD and matched controls (26 women and 8 men) in the summer and winter. Plasma leptin was positively correlated with BMI in patients and controls during both seasons. Women and men with SAD both experienced depression in the winter, which was associated with increased appetite, caloric intake, and carbohydrate craving. Increased body weight during the winter in subjects with SAD was paralleled by a lack of concomitant changes in plasma leptin, which suggests that leptin sensitivity to changes in body weight may be influenced by seasons in subjects with SAD, similar to seasonal mammals. C1 NIDDK, Bethesda, MD 20892 USA. NIMH, Clin Psychobiol Branch, Pediat & Reprod Endocrinol Branch, Bethesda, MD USA. RP Cizza, G (reprint author), NIDDK, NIH Bldg,10 Rm 9C-101 10 Ctr Dr, Bethesda, MD 20892 USA. EM CizzaG@mail.nih.gov NR 23 TC 17 Z9 19 U1 0 U2 6 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 2005 VL 37 IS 1 BP 45 EP 48 DI 10.1055/s-2005-861033 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 898OV UT WOS:000227087000010 PM 15702439 ER PT J AU Nilsson, O Marino, R De Luca, F Phillip, M Baron, J AF Nilsson, O Marino, R De Luca, F Phillip, M Baron, J TI Endocrine regulation of the growth plate SO HORMONE RESEARCH LA English DT Review DE hormones; growth plate; longitudinal bone growth; growth hormone; insulin-like growth factor; glucocorticoid; thyroid hormone; estrogen; androgen; vitamin D; leptin ID LONGITUDINAL BONE-GROWTH; MESSENGER-RIBONUCLEIC-ACID; GH RECEPTOR DEFICIENCY; CARTILAGE IN-VIVO; PROTEIN-KINASE-C; CATCH-UP GROWTH; IGF-I; POSTNATAL-GROWTH; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; CHONDROCYTE DIFFERENTIATION AB Longitudinal bone growth occurs at the growth plate by endochondral ossification. Within the growth plate, chondrocyte proliferation, hypertrophy, and cartilage matrix secretion result in chondrogenesis. The newly formed cartilage is invaded by blood vessels and bone cells that remodel the newly formed cartilage into bone tissue. This process of longitudinal bone growth is governed by a complex network of endocrine signals, including growth hormone, insulin-like growth factor I, glucocorticoid, thyroid hormone, estrogen, androgen, vitamin D, and leptin. Many of these signals regulate growth plate function, both by acting locally on growth plate chondrocytes and also indirectly by modulating other endocrine signals in the network. Some of the local effects of hormones are mediated by changes in paracrine factors that control chondrocyte proliferation and differentiation. Many human skeletal growth disorders are caused by abnormalities in the endocrine regulation of the growth plate. This review provides an overview of the endocrine signals that regulate longitudinal bone growth, their interactions, and the mechanisms by which they affect growth plate chondrogenesis. Copyright (C) 2005 S. Karger AG, Basel. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. St Christophers Hosp Children, Sect Endocrinol & Diabet, Philadelphia, PA 19133 USA. Schneider Childrens Med Ctr Israel, Inst Endocrinol & Diabet, Petah Tiqwa, Israel. RP Nilsson, O (reprint author), NICHD, NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC 1862, Bethesda, MD 20892 USA. EM ola.nilsson@nih.gov OI Nilsson, Ola/0000-0002-9986-8138 NR 90 TC 155 Z9 165 U1 5 U2 27 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PY 2005 VL 64 IS 4 BP 157 EP 165 DI 10.1159/000088791 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 980TH UT WOS:000233040600001 PM 16205094 ER PT J AU Nwosu, BU Nilsson, O Mitchum, RD Coco, M Barnes, KM Baron, J AF Nwosu, BU Nilsson, O Mitchum, RD Coco, M Barnes, KM Baron, J TI Lack of telomere shortening with age in mouse resting zone chondrocytes SO HORMONE RESEARCH LA English DT Article DE telomere; chondrocytes; senescence; growth plate ID GROWTH-PLATE; SENESCENCE; CANCER; CELLS; MICE; RNA AB Background and Aim: Telomeres are hexameric repeat sequences that flank eukaryotic chromosomes. The telomere hypothesis of cellular aging proposes that replication of normal somatic cells leads to progressive telomere shortening which induces replicative senescence. Previous studies suggest that growth plate chondrocytes have a finite proliferative capacity in vivo. We therefore hypothesized that telomere shortening in resting zone chondrocytes leads to replicative senescence. Method: To test this hypothesis we compared the telomere restriction fragment (TRF) length of Mus casteneus at 1, 4, 8, and 56 weeks of age. Results and Conclusions: We found that TRF length did not diminish measurably with age, suggesting that telomere shortening in resting zone chondrocytes is not the mechanism that limits proliferation of growth plate chondrocytes in vivo. Copyright (C) 2005 S. Karger AG, Basel. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Nwosu, BU (reprint author), Univ Massachusetts, Sch Med, Div Endocrinol, 55 Lake Ave N, Worcester, MA 01605 USA. EM nwosub@ummhc.org OI Nwosu, Benjamin/0000-0003-2212-0276; Nilsson, Ola/0000-0002-9986-8138 NR 21 TC 4 Z9 5 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 2005 VL 63 IS 3 BP 125 EP 128 DI 10.1159/000084687 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 922ON UT WOS:000228847400004 PM 15795509 ER PT J AU Suomi, SJ AF Suomi, SJ TI Mother-infant attachment, peer relationships, and the development of social networks in rhesus monkeys SO HUMAN DEVELOPMENT LA English DT Article DE attachment; matrilines; peers; rhesus monkeys; social networks ID BEHAVIOUR; MACAQUES; PRIMATES; MACACA AB The social networks that rhesus monkeys develop in nature are centered around multiple generations of matrilineal kin embedded in larger social groupings that have some degree of distinctiveness and permanence. Within each family, infants initially grow up in the care of their mothers and the close presence of relatives, and they subsequently expand their social network to include peers and others in the larger community and beyond while continuing to retain strong family ties throughout adolescence ( for males) and for the rest of their lives ( for females). Rhesus monkey families differ in relative status within their community-like troops, and these differences can have long-term consequences for individuals within each family. Yet there is also evidence that changes in within-family relationships, particularly those between mothers and offspring, can eventually lead to changes in the basic nature of the troop itself. It seems appropriate to characterize the social relationships that emerge between rhesus monkey mothers and their offspring in attachment-like terms, especially given Bowlby's reliance on observations of rhesus monkey mother-infant interactions to provide the biological basis of the attachment theory he was formulating in the late 1950s and 1960s. Contrastingly, it may be overly simplistic to describe the various other social relationships that rhesus monkeys routinely develop within their expanding social networks exclusively from an attachment perspective. Instead, these other social relationships clearly differ from their relationship with their mother with respect to the specific behaviors that characterize each type of relationship, the physical and social contexts in which the relationships are expressed, and the manner in which each relationship changes throughout development. Moreover, the different relationships each monkey develops as it matures appear to complement one another as it becomes integrated into its overall social network. Copyright (C) 2005 S. Karger AG, Basel. C1 NICHHD, Comparat Ethol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Suomi, SJ (reprint author), NICHHD, Comparat Ethol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM SS148k@nih.gov NR 35 TC 35 Z9 36 U1 5 U2 23 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0018-716X J9 HUM DEV JI Hum. Dev. PY 2005 VL 48 IS 1-2 BP 67 EP 79 DI 10.1159/000083216 PG 13 WC Psychology, Developmental SC Psychology GA 917CP UT WOS:000228433900005 ER PT J AU Ramzan, K Shaikh, RS Ahmad, J Khan, SN Riazuddin, S Ahmed, ZM Friedman, TB Wilcox, ER Riazuddin, S AF Ramzan, K Shaikh, RS Ahmad, J Khan, SN Riazuddin, S Ahmed, ZM Friedman, TB Wilcox, ER Riazuddin, S TI A new locus for nonsyndromic deafness DFNB49 maps to chromosome 5q12.3-q14.1 SO HUMAN GENETICS LA English DT Article ID SYNDROME-TYPE-II; USHER-SYNDROME; RECESSIVE DEAFNESS; HEARING-LOSS; TRANSCRIPTION FACTOR; ALLELIC MUTATIONS; PDS MUTATIONS; GENE; HETEROGENEITY; PCDH15 AB Cosegregation of markers on chromosome 5q12.3-q14.1 with profound congenital deafness in two Pakistani families (PKDF041 and PKDF141) defines a new recessive deafness locus, DFNB49. A maximum two-point lod score of 4.44 and 5.94 at recombination fraction theta=0 was obtained for markers D5S2055 and D5S424 in families PKDF041 and PKDF141, respectively. Haplotype analysis revealed an 11 cM linkage region flanked by markers D5S647 (74.07 cM) and D5S1501 (85.25 cM). Candidate deafness genes in this region include SLC30A5, OCLN, GTF2H2, and BTF3, encoding solute carrier family 30 (zinc transporter) member 5, occludin, RNA polymerase 11 transcription initiation factor, and basic transcription factor 3, respectively. Sequence analysis of the coding exons of SLC30A5 in DNA samples from two affected individuals of families PKDF041 and PKDF141 revealed no mutation. The mapping of DFNB49 further confirms the heterogeneity underlying autosomal recessive forms of nonsyndromic deafness. C1 Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan. Natl Inst Deafness & Other Commun, Mol Genet Lab, Sect Human Genet, NIH, Rockville, MD 20850 USA. RP Riazuddin, S (reprint author), Univ Punjab, Natl Ctr Excellence Mol Biol, 87 W Canal Bank Rd,Thokar Niaz Baig, Lahore 53700, Pakistan. EM riaz@lhr.comsats.net.pk RI Shaikh, Rehan Sadiq/B-9101-2009; Ahmad, Jamil/D-4130-2009; Nasim Khan, Shaheen/F-2135-2015 FU NIDCD NIH HHS [1ZO1 DC000035-07, 1ZO1 DC000039-07] NR 30 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JAN PY 2005 VL 116 IS 1-2 BP 17 EP 22 DI 10.1007/s00439-004-1205-8 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 890ZX UT WOS:000226552200003 PM 15538632 ER PT J AU Rokman, A Baffoe-Bonnie, AB Gillanders, E Fredriksson, H Autio, V Ikonen, T Gibbs, KD Jones, MP Gildea, D Freas-Lutz, D Markey, C Matikainen, MP Koivisto, PA Tammela, TLJ Kallioniemi, OP Trent, J Bailey-Wilson, JE Schleutker, J AF Rokman, A Baffoe-Bonnie, AB Gillanders, E Fredriksson, H Autio, V Ikonen, T Gibbs, KD Jones, MP Gildea, D Freas-Lutz, D Markey, C Matikainen, MP Koivisto, PA Tammela, TLJ Kallioniemi, OP Trent, J Bailey-Wilson, JE Schleutker, J TI Hereditary prostate cancer in Finland: fine-mapping validates 3p26 as a major predisposition locus SO HUMAN GENETICS LA English DT Article ID GENOME-WIDE SCAN; SUSCEPTIBILITY LOCUS; GERMLINE MUTATIONS; FAMILIES; GENE; LINKAGE; CHROMOSOME; RISK; DISEASE; HPC1 AB In a recent genome-wide linkage (GWL) analysis of Finnish families at high risk for prostate cancer, we found two novel putative susceptibility loci at 3p25-p26 and 11q14. Here, we report the fine-mapping of these two critical regions at high resolution with 39 microsatellite markers in 16 families, including multiplex families that were not used in the GWL scan. The maximum multipoint HLOD was 3.39 at 3p26 and 1.42 at 11q14. The highest LOD scores were seen around markers D3S1270 and D3S4559 (alpha=0.89), covering approximately two megabases. The two known genes in this region CHL1 (cell adhesion molecule with homology to L1CAM) and CNTN6 (contactin 6) were screened for exonic mutations in the families showing the strongest linkage, but no disease-segregating sequence variants were observed. The recombination map pointed to a region proximal to the area of best linkage, suggesting that more genes may need to be investigated as candidates. These results provide strong evidence for the existence of a prostate cancer susceptibility gene at 3p26 in Finnish prostate cancer families. This locus has not been strongly linked with hereditary prostate cancer in other populations. However, the mildly positive 3p LOD scores in a recent GWL analysis of patients from the United States suggest that the locus may also be important in other populations. C1 Univ Tampere, Inst Med Technol, Canc Genet Lab, Tampere 33014, Finland. Tampere Univ Hosp, Res Unit, Tampere 33014, Finland. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Tampere Univ Hosp, Div Urol, Tampere, Finland. Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Dept Clin Genet, Tampere, Finland. VTT, Tech Res Ctr, Med Biotechnol, Turku, Finland. Univ Turku, Turku, Finland. Translat Genom Res Inst, Phoenix, AZ USA. RP Rokman, A (reprint author), Univ Tampere, Inst Med Technol, Canc Genet Lab, Tampere 33014, Finland. EM annika.rokman@uta.fi RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012; OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; Bailey-Wilson, Joan/0000-0002-9153-2920; Gibbs, Kenneth/0000-0002-3532-5396 FU NCI NIH HHS [CA-06927]; NHGRI NIH HHS [N01-HG-55389] NR 17 TC 15 Z9 17 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JAN PY 2005 VL 116 IS 1-2 BP 43 EP 50 DI 10.1007/s00439-004-1214-7 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 890ZX UT WOS:000226552200007 PM 15549392 ER PT J AU Zheng, G Joo, J Ganesh, SK Nabel, EG Geller, NL AF Zheng, G Joo, J Ganesh, SK Nabel, EG Geller, NL TI On averaging power for genetic association and linkage studies SO HUMAN HEREDITY LA English DT Article DE average power; linkage analysis; case-control study; trend test ID SAMPLE-SIZE CALCULATIONS; AFFECTED SIBS; TESTS; DISTRIBUTIONS; ROBUSTNESS; GENOTYPES; DESIGN AB A power calculation is crucial in planning genetic studies. In genetic association studies, the power is often calculated using the expected number of individuals with each genotype calculated from an assumed allele frequency under Hardy-Weinberg equilibrium. Since the allele frequency is often unknown, the number of individuals with each genotype is random and so a power calculation assuming a known allele frequency may be incorrect. Ambrosius et al. [ 1] recently showed that the power ignoring this randomness may lead to studies with insufficient power and proposed averaging the power due to the randomness. We extend the method of averaging power in two directions. First, for testing association in case-control studies, we use the Cochran-Armitage trend test and find that the time needed for calculating the averaged power is much reduced compared to the chi-square test with two degrees of freedom studied by Ambrosius et al. [ 1]. A real study is used for illustration of the method. Second, we extend the method to linkage analysis, where the number of identical-by-descent alleles shared by siblings is random. The distribution of identical-by-descent numbers depends on the underlying genetic model rather than the allele frequency. The robust test for linkage analysis is also examined using the averaged powers. We also recommend a sensitivity analysis when the true allele frequency or the number of identical-by-descent alleles is unknown. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr,MSC 7938, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov NR 21 TC 6 Z9 6 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2005 VL 59 IS 1 BP 14 EP 20 DI 10.1159/000084732 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 918WY UT WOS:000228579700002 PM 15802917 ER PT J AU Mathias, RA Beaty, TH Bailey-Wilson, JE Bickel, C Stockton, ML Barnes, KC AF Mathias, RA Beaty, TH Bailey-Wilson, JE Bickel, C Stockton, ML Barnes, KC TI Inheritance of total serum IgE in the isolated Tangier Island population from Virginia: Complexities associated with genealogical depth of pedigrees in segregation analyses SO HUMAN HEREDITY LA English DT Article DE isolate; inbreeding; IgE; segregation analysis ID SKIN-TEST REACTIVITY; SIB-PAIR METHOD; IMMUNOGLOBULIN-E; ATOPIC DISEASE; ASTHMA; FAMILIES; TWINS; ALLERGENS; TRANSMISSION; CHILDREN AB Objectives: This study was aimed at performing a segregation analysis of total serum immunoglobulin E (tlgE) in an isolated population using maximal genealogical information permitted by current software and computer capacities, while assessing the reliability of the best-fitting model of inheritance for tlgE through simulations. Methods: All current Tangier Island, VA, residents (n = 664) belonged to one large extended pedigree (n = 3,501) spanning 13 generations, with an average inbreeding coefficient of 0.009. Phenotype data were obtained on 453 (68.2%) of the residents using a population-based recruitment scheme. Due to computational limitations resulting from the extremely complex pedigree structure, analysis on only two pedigree reconstructions was feasible: a reduced pedigree retaining all phenotyped individuals and their parents as 57 distinct families, and 922 nuclear families. Results: Familial correlations and heritability calculations reveal a significant genetic component to tlgE in these data (heritability = 26%). The most parsimonious model to explain tlgE distribution indicated by the reduced pedigree structure was a two-distribution Mendelian model. However, larger and non-genetic models could not be rejected. Simulations over 200 replicates performed to evaluate the reliability of this model, indicated that using restricted genealogical information had minimal impact on results of segregation analyses performed here. C1 Johns Hopkins Univ, Bloomberg Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Inherited Dis Res Branch, NHGRI,NIH, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Div Clin Immunol & Allergy, Baltimore, MD USA. RP Mathias, RA (reprint author), 333 Cassell Dr,Suite 1200, Baltimore, MD 21224 USA. EM rmathias1@mail.nih.gov OI Bailey-Wilson, Joan/0000-0002-9153-2920 NR 43 TC 6 Z9 6 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2005 VL 59 IS 4 BP 228 EP 238 DI 10.1159/000087123 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 957QY UT WOS:000231389600006 PM 16093728 ER PT J AU Adams, S Russ, C Uribe, M Marincola, F Stroncek, D AF Adams, S Russ, C Uribe, M Marincola, F Stroncek, D TI PCR validation testing utilizing a novel dynamic measurement system SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 17-21, 2005 CL Washington, DC SP Amer Soc Histocompatibil & Immunogenet C1 NIH, DTM HLA Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2005 VL 66 SU 1 BP S74 EP S74 PG 1 WC Immunology SC Immunology GA 983HF UT WOS:000233221400139 ER PT J AU Chun, H Peterson, B Marincola, F Stroncek, D Adams, S AF Chun, H Peterson, B Marincola, F Stroncek, D Adams, S TI DNA yields for WB vs buffy coat protocol utilizing the GenoM (TM)(-6) SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 17-21, 2005 CL Washington, DC SP Amer Soc Histocompatibil & Immunogenet C1 NIH, DTM HLA Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2005 VL 66 SU 1 BP S36 EP S36 PG 1 WC Immunology SC Immunology GA 983HF UT WOS:000233221400065 ER PT J AU Helmberg, W Nelson, L Pugliese, A Hoffman, D Feolo, M AF Helmberg, W Nelson, L Pugliese, A Hoffman, D Feolo, M TI Two new clinical resources at dbMHC: The rheumatoid arthritis project and the diabetes project of the 13.IHWC SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 17-21, 2005 CL Washington, DC SP Amer Soc Histocompatibil & Immunogenet C1 Med Univ Graz, UBT, Graz, Austria. FHCRC, Seattle, WA USA. Univ Miami, DRI, Miami, FL 33152 USA. NCBI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2005 VL 66 SU 1 BP S67 EP S67 PG 1 WC Immunology SC Immunology GA 983HF UT WOS:000233221400126 ER PT J AU Helmberg, W Hoffman, D Feolo, M Maiers, M AF Helmberg, W Hoffman, D Feolo, M Maiers, M TI Population based characterisation of HLA typing kits and ambiguous typing results: The frequency inferred typing (FIT) index SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 17-21, 2005 CL Washington, DC SP Amer Soc Histocompatibil & Immunogenet C1 NCBI, NIH, Bethesda, MD USA. NMDP, Minneapolis, MN USA. Med Univ Graz, UBT, Graz, Austria. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2005 VL 66 SU 1 BP S36 EP S36 PG 1 WC Immunology SC Immunology GA 983HF UT WOS:000233221400066 ER PT J AU Helmberg, W Feolo, M Dunivan, R AF Helmberg, W Feolo, M Dunivan, R TI dbLRC-KIR, a new specialised database for genes of the leucocyte receptor complex SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 17-21, 2005 CL Washington, DC SP Amer Soc Histocompatibil & Immunogenet C1 Med Univ Graz, UBT, Graz, Austria. NCBI, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2005 VL 66 SU 1 BP S17 EP S17 PG 1 WC Immunology SC Immunology GA 983HF UT WOS:000233221400029 ER PT J AU Shulzhenko, N Morgun, A Perez-Diez, A Diniz, R Almeida, D Sanson, G Matzinger, P Gerbase-DeLima, M AF Shulzhenko, N Morgun, A Perez-Diez, A Diniz, R Almeida, D Sanson, G Matzinger, P Gerbase-DeLima, M TI Universal profiles of rejection and infection in organ transplants. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 17-21, 2005 CL Washington, DC SP Amer Soc Histocompatibil & Immunogenet C1 Univ Fed Sao Paulo, BR-04023062 Sao Paulo, Brazil. NIH, LCMI, Bethesda, MD 20892 USA. RI Gerbase-DeLima, Maria/K-2515-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2005 VL 66 SU 1 BP S108 EP S108 PG 1 WC Immunology SC Immunology GA 983HF UT WOS:000233221400204 ER PT J AU Shulzhenko, N Morgun, A Perez-Diez, A Diniz, R Almeida, D Sanson, G Matzinger, P Gerbase-DeLima, M AF Shulzhenko, N Morgun, A Perez-Diez, A Diniz, R Almeida, D Sanson, G Matzinger, P Gerbase-DeLima, M TI Universal profiles of rejection and infection in organ transplants. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 17-21, 2005 CL Washington, DC SP Amer Soc Histocompatibil & Immunogenet C1 Univ Fed Sao Paulo, Sao Paulo, Brazil. LCMI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2005 VL 66 SU 1 BP S4 EP S4 PG 1 WC Immunology SC Immunology GA 983HF UT WOS:000233221400005 ER PT J AU Uribe, MR Adams, S Pae, E Stroncek, D Marincola, F AF Uribe, MR Adams, S Pae, E Stroncek, D Marincola, F TI KIR genotype lacking of some conserved genes SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 17-21, 2005 CL Washington, DC SP Amer Soc Histocompatibil & Immunogenet C1 NIH, DTM HLA Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2005 VL 66 SU 1 BP S23 EP S23 PG 1 WC Immunology SC Immunology GA 983HF UT WOS:000233221400040 ER PT J AU Uribe, MR Adams, S Shupert, L Stroncek, D Connors, M Marincola, F AF Uribe, MR Adams, S Shupert, L Stroncek, D Connors, M Marincola, F TI KIR gene content and HIV progression SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 17-21, 2005 CL Washington, DC SP Amer Soc Histocompatibil & Immunogenet C1 NIH, DTM HLA Lab, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2005 VL 66 SU 1 BP S23 EP S23 PG 1 WC Immunology SC Immunology GA 983HF UT WOS:000233221400041 ER PT S AU Chaussabel, D Allman, W Mejias, A Chung, W Bennett, L Ramilo, O Pascual, V Palucka, AK Banchereau, J AF Chaussabel, D Allman, W Mejias, A Chung, W Bennett, L Ramilo, O Pascual, V Palucka, AK Banchereau, J BE Steinman, RM TI Analysis of significance patterns identifies ubiquitous and disease-specific gene-expression signatures in patient peripheral blood leukocytes SO HUMAN IMMUNOLOGY: PATIENT-BASED RESEARCH SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Human Immunology CY MAY 16-18, 2005 CL New York, NY SP NY Acad Sci, Dana Fdn DE systemic lupus erythematosus; influenze A; gene expression; pathogenesis; immunology; leukocyte ID CLASS PREDICTION; INTERFERON; DISCOVERY; CANCER; LUPUS AB The utilization of gene-expression microarrays in patient-based research creates new prospects for the discovery of diagnostic biomarkers and the identification of genes or pathways linked to pathogenesis. Gene-expression signatures in peripheral blood mononuclear cells isolated from over one hundred patients with conditions presenting a strong immunological component (patient with autoimmune, graft versus host and infectious diseases, as well as immuno-suppressed transplant recipients) were generated. This dataset provides the opportunity to carry out comparative analyses and define disease signatures in a broader context. Transcriptional changes of 22,283 probe sets were evaluated through statistical group comparison performed systematically for seven diseases versus their respective healthy control group. Patterns of significance were generated by hierarchical clustering of P-values. This approach led to the identification of a SLE-specific "diagnostic signature," formed by genes that did not change compared to healthy subjects in the other six diseases. Conversely, a "sentinel signature" that was common to all seven diseases was characterized. These findings bring new perspectives for the application of blood leukocyte expression signatures for diagnosis and early disease detection. C1 Baylor Inst Immunol Res, Dallas, TX 75204 USA. Baylor NIAID Cooperat Ctr Translat Res Human Immu, Dallas, TX 75204 USA. Univ Texas, SW Med Ctr, Div Pediat Infect, Dallas, TX USA. Childrens Med Ctr, Dallas, TX 75235 USA. RP Chaussabel, D (reprint author), Baylor Inst Immunol Res, 3434 Live Oak St,Suite 205, Dallas, TX 75204 USA. EM damienc@baylorhealth.edu RI Mejias, Maria Asuncion/E-3659-2011; OI Chaussabel, Damien/0000-0002-6131-7242 FU NCI NIH HHS [CA78846]; PHS HHS [U19 AIO57234-02] NR 8 TC 30 Z9 30 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 1-57331-606-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1062 BP 146 EP 154 DI 10.1196/annals.1358.017 PG 9 WC Immunology; Multidisciplinary Sciences SC Immunology; Science & Technology - Other Topics GA BEA65 UT WOS:000236473100015 PM 16461797 ER PT J AU Liu, J Nealon, JG Weinstein, LS AF Liu, J Nealon, JG Weinstein, LS TI Distinct patterns of abnormal GNAS imprinting in familial and sporadic pseudohypoparathyroidism type IB SO HUMAN MOLECULAR GENETICS LA English DT Article ID ALPHA-SUBUNIT G(S)ALPHA; G-PROTEIN; LOCUS; GENE; ANTISENSE; METHYLATION; NESP; EXPRESSION; CLUSTER; REGION AB Pseudohypoparathyroidism type IB (PHPIB) is associated with abnormal imprinting of GNAS, the gene encoding the heterotrimeric G protein G(s)alpha and other alternative products. The gene contains three differentially methylated regions (DMRs) located upstream of the G(s)alpha promoter (from upstream to downstream): the paternally methylated NESP55 promoter region, the maternally methylated NESP antisense (NESPAS)/XLalphas promoter region and the maternally methylated exon 1A region located just upstream of the G(s)alpha promoter. We have now performed a detailed analysis of the GNAS methylation profile in 20 unrelated PHPIB probands. Consistent with prior results, all have loss of exon 1A imprinting (a paternal epigenotype on both alleles). All five probands with familial disease had a deletion mutation within the closely linked STX16 gene and a GNAS imprinting defect involving only the exon 1A region. In contrast, the STX16 mutation was absent in all sporadic cases. The majority of these patients had abnormal imprinting of the more upstream regions in addition to the exon 1A imprinting defect, with eight of 15 having a paternal epigenotype on both alleles throughout the GNAS locus. In virtually all cases, the imprinting status of the NESP55 and NESPAS/XLalphas promoters is concordant, suggesting that their imprinting is co-regulated, whereas the imprinting of the NESPAS/XLalphas promoter region and XLalphas first exon is not always concordant even though they are closely linked and lie within the same DMR. Familial and sporadic forms of PHPIB have distinct GNAS imprinting patterns that occur through different defects in the imprinting mechanism. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Weinstein, LS (reprint author), NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. EM leew@amb.niddk.nih.gov OI Weinstein, Lee/0000-0002-1899-5152 NR 32 TC 85 Z9 88 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 1 PY 2005 VL 14 IS 1 BP 95 EP 102 DI 10.1093/hmg/ddi009 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 886AS UT WOS:000226199300009 PM 15537666 ER PT J AU Shashidharan, P Sandu, D Potla, U Armata, IA Walker, RH McNaught, KS Weisz, D Sreenath, T Brin, MF Olanow, CW AF Shashidharan, P Sandu, D Potla, U Armata, IA Walker, RH McNaught, KS Weisz, D Sreenath, T Brin, MF Olanow, CW TI Transgenic mouse model of early-onset DYT1 dystonia SO HUMAN MOLECULAR GENETICS LA English DT Article ID PRIMARY TORSION DYSTONIA; NUCLEAR-ENVELOPE; LEWY BODIES; PC12 CELLS; GENE DYT1; PEDUNCULOPONTINE NUCLEUS; PARKINSONS-DISEASE; HUMAN BRAIN; RAT-BRAIN; PROTEIN AB Early-onset dystonia is an autosomal dominant movement disorder associated with deletion of a glutamic acid residue in torsinA. We generated four independent lines of transgenic mice by overexpressing human DeltaE-torsinA using a neuron specific enolase promoter. The transgenic mice developed abnormal involuntary movements with dystonic-appearing, self-clasping of limbs, as early as 3 weeks after birth. Animals also showed hyperkinesia and rapid bi-directional circling. Approximately 40% of transgenic mice from each line demonstrated these severe behavioral abnormalities. Neurochemical analyses revealed decreases in striatal dopamine in affected transgenic mice, although levels were increased in those that had no behavioral changes. Immunohistochemistry demonstrated perinuclear inclusions and aggregates that stained positively for ubiquitin, torsinA and lamin, a marker of the nuclear envelope. Inclusions were detected in neurons of the pedunculopontine nucleus and in other brain stem regions in a pattern similar to what has been described in DYT1 patients. This transgenic mouse model demonstrates behavioral and pathologic features similar to patients with early-onset dystonia and may help to better understand the pathophysiology of this disorder and to develop more effective therapies. C1 CUNY Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Neurosurg, New York, NY 10029 USA. Vet Affairs, Bronx, NY USA. NIDCR, Funct Genom Unit, Bethesda, MD USA. Allergan Pharmaceut Inc, Irvine, CA USA. RP Shashidharan, P (reprint author), CUNY Mt Sinai Sch Med, Dept Neurol, Box 1137,1 Gustave L Levy Pl, New York, NY 10029 USA. EM pullani.shashi@mssm.edu FU NCI NIH HHS [R24 CA88302]; NINDS NIH HHS [R01 NS43038] NR 44 TC 83 Z9 84 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 1 PY 2005 VL 14 IS 1 BP 125 EP 133 DI 10.1093/hmg/ddi012 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 886AS UT WOS:000226199300012 PM 15548549 ER PT J AU Diatchenko, L Slade, GD Nackley, AG Bhalang, K Sigurdsson, A Belfer, I Goldman, D Xu, K Shabalina, SA Shagin, D Max, MB Makarov, SS Maixner, W AF Diatchenko, L Slade, GD Nackley, AG Bhalang, K Sigurdsson, A Belfer, I Goldman, D Xu, K Shabalina, SA Shagin, D Max, MB Makarov, SS Maixner, W TI Genetic basis for individual variations in pain perception and the development of a chronic pain condition SO HUMAN MOLECULAR GENETICS LA English DT Article ID CATECHOL-O-METHYLTRANSFERASE; EXPERIMENTALLY EVOKED PAIN; TEMPOROMANDIBULAR DISORDERS; TEMPORAL SUMMATION; RISK-FACTOR; SENSITIVITY; COMT; SCHIZOPHRENIA; ASSOCIATION; NOCICEPTION AB Pain sensitivity varies substantially among humans. A significant part of the human population develops chronic pain conditions that are characterized by heightened pain sensitivity. We identified three genetic variants (haplotypes) of the gene encoding catecholamine-O-methyltransferase (COMT) that we designated as low pain sensitivity (LPS), average pain sensitivity (APS) and high pain sensitivity (HPS). We show that these haplotypes encompass 96% of the human population, and five combinations of these haplotypes are strongly associated (P=0.0004) with variation in the sensitivity to experimental pain. The presence of even a single LPS haplotype diminishes, by as much as 2.3 times, the risk of developing myogenous temporomandibular joint disorder (TMD), a common musculoskeletal pain condition. The LPS haplotype produces much higher levels of COMT enzymatic activity when compared with the APS or HPS haplotypes. Inhibition of COMT in the rat results in a profound increase in pain sensitivity. Thus, COMT activity substantially influences pain sensitivity, and the three major haplotypes determine COMT activity in humans that inversely correlates with pain sensitivity and the risk of developing TMD. C1 Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC 27599 USA. Univ Adelaide, Australian Res Ctr Populat Oral Hlth, Adelaide, SA 5005, Australia. Chulalongkorn Univ, Dept Oral Med, Bangkok 10330, Thailand. NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NCBI, NIH, Bethesda, MD 20894 USA. RAS, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia. NIDCR, NIH, Pain & Neurosensory Mech Branch, Bethesda, MD 20892 USA. Attagene Inc, Res Triangle Pk, NC 27560 USA. RP Diatchenko, L (reprint author), Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Columbia St,CB 7455,2190 Old Dent Bldg, Chapel Hill, NC 27599 USA. EM lbdiatch@email.unc.edu RI Shabalina, Svetlana/N-8939-2013; Goldman, David/F-9772-2010 OI Shabalina, Svetlana/0000-0003-2272-7473; Goldman, David/0000-0002-1724-5405 FU NIAAA NIH HHS [AA000301]; NIAMS NIH HHS [AR/AI-44564, 5-P60 AR-30701-14, AR/AI-44030]; NIDCR NIH HHS [DE00366, DE007333, DE07509] NR 39 TC 639 Z9 664 U1 2 U2 43 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 1 PY 2005 VL 14 IS 1 BP 135 EP 143 DI 10.1093/hmg/ddi013 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 886AS UT WOS:000226199300013 PM 15537663 ER PT J AU Li, YH Hollingworth, P Moore, P Foy, C Archer, N Powell, J Nowotny, P Holmans, P O'Donovan, M Tacey, K Doil, L van Luchene, R Garcia, V Rowland, C Lau, K Cantanese, J Sninsky, J Hardy, J Thal, L Morris, JC Goate, A Lovestone, S Owen, M Williams, J Grupe, A AF Li, YH Hollingworth, P Moore, P Foy, C Archer, N Powell, J Nowotny, P Holmans, P O'Donovan, M Tacey, K Doil, L van Luchene, R Garcia, V Rowland, C Lau, K Cantanese, J Sninsky, J Hardy, J Thal, L Morris, JC Goate, A Lovestone, S Owen, M Williams, J Grupe, A TI Genetic association of the APP binding protein 2 gene (APBB2) with late onset Alzheimer disease SO HUMAN MUTATION LA English DT Article DE Alzheimer disease; AD; LOAD; association; APP; APBB2; SNP ID AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN-E; INTRON-13 POLYMORPHISM; MISSENSE MUTATIONS; FE65-LIKE PROTEIN; CANDIDATE GENES; FE65 GENE; LOCUS; CHROMOSOME-1; ALLELE AB Alzheimer disease (AD) is a complex neurodegenerative disorder predisposed by multiple genetic factors. Mutations in amyloid beta precursor protein (APP) are known to be associated with autosomal dominant, early onset familial AD and possibly also late onset AD (LOAD). A number of genes encoding proteins capable of binding to APP have been identified, but their contribution to AD pathobiology remains unclear. Conceivably, mutations in these genes may play a role in affecting AD susceptibility, which appears to be substantiated by some genetic studies. Here we report results of the first genetic association study with APBB2, an APP binding protein (also known as FE65L), and LOAD, in three independently collected case-control series totaling approximately 2,000 samples. Two SNPs were significantly associated with LOAD in two sample series and in meta-analyses of all three sample sets (for rs13133980: odds ratio [OR](hom) = 1.36 [95% CI: 1.05-1.75], ORhet = 1.32 [95% CI: 1.04-1.67], minor allele frequency = 43%, P = 0.041; and for hCV1558625: ORhom = 1.37 [95% CI: 1.061.77], ORhet = 1.02 [95% CI: 0.82-1.26], minor allele frequency 48%, P = 0.026). One of these SNPs, located in a region conserved between the human and mouse genome, showed a significant interaction with age of disease onset. For this marker, the association with LOAD was most pronounced in subjects with disease onset before 75 years of age (ORhom = 2.43 [95% CI: 1.61-3.67]; ORhet 2.15 [95% CI: 1.46-3.17]; P = 0.00006) in the combined sample set. Our data raise the possibility that genetic variations in APBB2 may affect LOAD susceptibility. (C) 2005 Wiley-Liss, Inc. C1 Celera Diagnost, Alameda, CA 94502 USA. Cardiff Univ, Wales Coll Med, Dept Med Psychol, Cardiff, S Glam, Wales. Kings Coll London, Inst Psychiat, Dept Neurosci, London, England. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Cardiff Univ, Wales Coll Med, Biostat & Bioinformat Unit, Cardiff, S Glam, Wales. NIA, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. RP Grupe, A (reprint author), Celera Diagnost, Alameda, CA 94502 USA. EM andrew.grupe@celeradiagnostics.com RI Lovestone, Simon/E-8725-2010; turton, miranda/F-4682-2011; Powell, John/G-4412-2011; Morris, John/A-1686-2012; Hardy, John/C-2451-2009; Holmans, Peter/F-4518-2015; OI Powell, John/0000-0001-6124-439X; Holmans, Peter/0000-0003-0870-9412; O'Donovan, Michael/0000-0001-7073-2379 FU NIA NIH HHS [P50AG05681, P01AG03991, P50 AG05131, R01AG16208, U24 AG021886] NR 29 TC 20 Z9 20 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2005 VL 25 IS 3 BP 270 EP 277 DI 10.1002/humu.20138 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 902NC UT WOS:000227362800006 PM 15714520 ER PT S AU Olsen, ECB Lee, SE Wierwille, WW AF Olsen, ECB Lee, SE Wierwille, WW GP TRB TI Eye glance behavior during lane changes and straight-ahead driving SO HUMAN PERFORMANCE; SIMULATION AND VISUALIZATION SE TRANSPORTATION RESEARCH RECORD LA English DT Article; Proceedings Paper CT 84th Annual Meeting of the Transportation-Research-Board CY JAN 09-13, 2005 CL Washington, DC SP US Dept Transportat, US Fed Aviat Adm, US Fed Highway Adm, US Fed Motor Carrier Safety Adm, US Fed Railroad Adm, US Fed Transit Adm, US Natl Highway Traff Safety Adm, US Res & Innovat Technol Adm, NASA, USA Corps Engineers, US Coast Guard, US DOE, US EPA, Transportat Res Board, Transportat Dept 50 States, Puerto Rico & District Columbia AB Understanding drivers' eye behavior before lane changing is an important aspect of designing usable, safe lane-change colfision-avoidance systems (LCAS) that will fit well with drivers' expectations. This understanding could lead to improvements for LCAS as well as for a variety of other collision avoidance systems. Findings regarding driver eye glance behaviors are presented in a comparison of lane change maneuvers with straight-ahead (baseline) driving events. Specific eye glance patterns before lane change initiation were observed. When preparing to make a lane change to the left as compared with driving straight ahead, drivers doubled the number of glances toward the rearview mirror and were much more likely to look at other locations associated with moving to the left including the left mirror and blind spot. On the basis of the eye glance Patterns observed and previous results, the following recommendations are made: (a) visual presence detection indicator displays should be used to provide information about vehicles in the rear adjacent lane any time a vehicle is detected, (b) a presence indicator should be presented in a visual format, and (c) the left mirror and rearview mirror locations should be considered for providing lane change information to the driver. The process of acquiring and analyzing eye glance movements is well worth the investment in resources. However, prototype systems must be tested before implementation, and the exact location and format of warning systems warrant a separate research and development effort to ensure safety and reliability. C1 NICHHD, Bethesda, MD 20892 USA. Virginia Polytech Inst & State Univ, Virginia Tech Transportat Inst, Blacksburg, VA 24061 USA. RP Olsen, ECB (reprint author), NICHHD, 6100 Executive Blvd,Room 7B05, Bethesda, MD 20892 USA. NR 24 TC 2 Z9 2 U1 0 U2 3 PU TRANSPORTATION RESEARCH BOARD NATL RESEARCH COUNCIL PI WASHINGTON PA 500 FIFTH ST, NW, WASHINGTON, DC 20001 USA SN 0361-1981 BN 0-309-09411-9 J9 TRANSPORT RES REC PY 2005 IS 1937 BP 44 EP 50 PG 7 WC Engineering, Civil; Ergonomics; Transportation; Transportation Science & Technology SC Engineering; Transportation GA BEG16 UT WOS:000237194300007 ER PT J AU Louis, GMB Schisterman, EF Dukic, VM Schieve, LA AF Louis, GMB Schisterman, EF Dukic, VM Schieve, LA TI Research hurdles complicating the analysis of infertility treatment and child health SO HUMAN REPRODUCTION LA English DT Article DE assisted reproductive technologies; child health; correlated outcomes; design; hierarchical models ID IN-VITRO FERTILIZATION; ASSISTED REPRODUCTIVE TECHNOLOGY; TIME-TO-PREGNANCY; LONG-TERM RECALL; CONGENITAL-MALFORMATIONS; UNITED-STATES; INVITRO FERTILIZATION; MULTIPLE GESTATION; FOLLOW-UP; BORN AB Research aimed at the empirical evaluation of infertility treatment including assisted reproductive technologies (ART) on child health and development is hampered by investigators' inability to methodologically separate possible treatment effects from underlying fecundity impairments. While the literature continues to identify ART as a risk factor for many child health outcomes, less attention has been paid to the methodologic rigor needed to answer this question. We identify aspects of fecundity and the nuances of medical practice that need to be considered and captured when designing epidemiologic investigations aimed at assessing ART and child health. These include: (i) the use of prospective study designs in which the unit of analysis (cycle versus individual versus couple) is defined; (ii) data collection on relevant time-varying covariates at, before and during treatment; and (iii) the use of statistical techniques appropriate for hierarchical data and correlated exposures. While none of these issues in and by itself is unique to ART research, attention to these issues has been lacking in much of the published research limiting our ability to evaluate health consequences for children. Longitudinal studies of children conceived with ART will benefit from attention to these issues and, hopefully, produce answers to lingering questions about safety. C1 NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv,NIH, Rockville, MD 20852 USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. RP Louis, GMB (reprint author), NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv,NIH, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. EM gb156i@nih.gov OI Dukic, Vanja/0000-0002-0348-0834; Schisterman, Enrique/0000-0003-3757-641X; Buck Louis, Germaine/0000-0002-1774-4490 NR 54 TC 36 Z9 37 U1 0 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 2005 VL 20 IS 1 BP 12 EP 18 DI 10.1093/humrep/deh542 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 886AP UT WOS:000226199000004 ER PT J AU Louis, GMB Weiner, JM Whitcomb, BW Sperrazza, R Schisterman, EF Lobdell, DT Crickard, K Greizerstein, H Kostyniak, PJ AF Louis, GMB Weiner, JM Whitcomb, BW Sperrazza, R Schisterman, EF Lobdell, DT Crickard, K Greizerstein, H Kostyniak, PJ TI Environmental PCB exposure and risk of endometriosis SO HUMAN REPRODUCTION LA English DT Article DE endocrine disruptors; endometriosis; environment; fecundity; polychlorinated biphenyls ID SERUM DIOXIN CONCENTRATIONS; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; MACACA-MULATTA; PELVIC PAIN; WOMEN; HEALTH; EXPRESSION; OUTCOMES; DISEASE; MICE AB BACKGROUND: Hormonally active environmental agents have recently been associated with the development of endometriosis. METHODS: We undertook a study to assess the relationship between endometriosis, an estrogen-dependent gynaecological disease, and 62 individual polychlorinated biphenyl (PCBs) congeners. We enrolled 84, eligible women aged 18-40 years undergoing laparoscopy for study, which included an interview and blood specimen (n = 79; 94%). Thirty-two women had visually confirmed endometriosis at laparoscopy while 52 did not. Blood specimens were run in batches of 14 including four quality control samples for toxicological analysis. Each PCB congener was adjusted for recovery; batch-specific reagent blanks were subtracted. All PCB concentrations were log transformed and expressed in ng/g serum first as a sum and then as tertiles by purported estrogenic or anti-estrogenic activity of PCB congeners. RESULTS: Using unconditional logistic regression analysis. a significantly elevated odds ratio (OR) was observed for women in the third tertile of anti-estrogenic PCBs [OR 3.77; 95% confidence interval (CI) 1.12-12.68]. Risk remained elevated after controlling for gravidity. current cigarette smoking and serum lipids (OR 3.30; 95% CI 0.87-12.46). CONCLUSIONS: These data suggest that anti-estrogenic PCBs may be associated with the development of endometriosis. C1 NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA. SUNY Buffalo, Buffalo, NY USA. US EPA, Washington, DC USA. RP Louis, GMB (reprint author), NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. EM gb156i@nih.2ov OI Schisterman, Enrique/0000-0003-3757-641X; Buck Louis, Germaine/0000-0002-1774-4490 FU NIEHS NIH HHS [1R01ES09044-01] NR 44 TC 78 Z9 82 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 EI 1460-2350 J9 HUM REPROD JI Hum. Reprod. PD JAN PY 2005 VL 20 IS 1 BP 279 EP 285 DI 10.1093/humrep/deh575 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 886AP UT WOS:000226199000040 PM 15513976 ER PT J AU Sundstrom, J Sullivan, L D'Agostino, RB Levy, D Kannel, WB Vasan, RS AF Sundstrom, J Sullivan, L D'Agostino, RB Levy, D Kannel, WB Vasan, RS TI Relations of serum uric acid to longitudinal blood pressure tracking and hypertension incidence SO HYPERTENSION LA English DT Article DE uric acid; blood pressure; epidemiology ID CORONARY HEART-DISEASE; CARDIOVASCULAR-DISEASE; INDEPENDENT MECHANISM; RISK FACTOR; FOLLOW-UP; HYPERURICEMIA; EVENTS; PREDICTORS; MORTALITY; PROGRAM AB Serum uric acid (UA) has been implicated in the pathogenesis of hypertension. We investigated the relationship of serum UA to hypertension incidence and blood pressure ( BP) progression in 3329 Framingham Study participants ( mean age 48.7 years; 55.6% women) free of hypertension, myocardial infarction, heart failure, renal failure, or gout. At follow-up 4 years from baseline, 458 persons (13.8%) had developed hypertension, and 1201 persons (36.1%) had experienced progression to a higher BP stage. Age- and sex-adjusted rates of hypertension incidence increased progressively from 9.8% for the lowest quartile to 15.6% for the top quartile of serum UA; BP progression rates increased from 32.8% ( lowest quartile) to 39.6% ( top quartile). In multivariable analyses adjusting for age, sex, body mass index, diabetes, smoking, alcohol intake, serum creatinine, proteinuria, glomerular filtration rate, baseline BP, and interim weight change, a 1 SD higher serum UA was associated with an odds ratio (OR) of 1.17 (95% confidence interval [CI], 1.02 to 1.33) for developing hypertension, and an OR of 1.11 ( 95% CI, 1.01 to 1.23) for BP progression. In analyses of a subsample of 3157 individuals not on antihypertensive treatment at the follow-up examination, serum UA was positively associated with changes in systolic ( P = 0.02) and diastolic pressure 4 years later ( P = 0.04). In summary, serum UA level was an independent predictor of hypertension incidence and longitudinal BP progression at short-term follow-up in our community-based sample. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Boston Univ, NHLBI, Boston, MA 02215 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM vasan@bu.edu RI Sundstrom, Johan/A-6286-2009; OI Sundstrom, Johan/0000-0003-2247-8454; Ramachandran, Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149 FU NHLBI NIH HHS [R01HL71039, 1R01HL67288-01, 2K24HL04334, N01-HC-25195, N01-HV-28178] NR 38 TC 261 Z9 304 U1 4 U2 12 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 2005 VL 45 IS 1 BP 28 EP 33 DI 10.1161/01.HYP.0000150784.92944.9a PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 883SD UT WOS:000226035100007 PM 15569852 ER PT J AU Lloyd-Jones, DM Leip, EP Larson, MG Vasan, RS Levy, D AF Lloyd-Jones, DM Leip, EP Larson, MG Vasan, RS Levy, D TI Novel approach to examining first cardiovascular events after hypertension onset SO HYPERTENSION LA English DT Article DE hypertension, detection and control; risk factors; cardiovascular diseases ID ISOLATED SYSTOLIC HYPERTENSION; ANTIHYPERTENSIVE DRUG-TREATMENT; BLOOD-PRESSURE; RANDOMIZED-TRIALS; STROKE PREVENTION; COMPETING RISKS; UNITED-STATES; METAANALYSIS; OUTCOMES; FRAMINGHAM AB Hypertension confers risk for multiple types of cardiovascular events, but competing risks for these outcomes are unknown. We estimated the competing risks over 12 years after hypertension onset among cases and age-, sex-, and examination-matched controls using competing Cox cumulative incidence and proportional hazards models. We included all Framingham Heart Study subjects examined after 1977 with new-onset hypertension who were free of cardiovascular disease. There were 645 men and 702 women with new-onset hypertension ( mean age: men, 55 +/- 12 years; women, 59 +/- 12 years). Compared with matched nonhypertensive controls, subjects with new-onset hypertension were more likely to experience a cardiovascular event first rather than noncardiovascular death. Among new-onset hypertensives, the 12-year competing cumulative incidence of any cardiovascular end point as a first event in men was 24.7%, compared with 9.8% for noncardiovascular death ( hazards ratio [HR], 2.53; 95% confidence interval [CI], 1.83 to 3.50); in women, the competing incidences were 16.0% versus 10.1%, respectively ( HR, 1.58; 95% CI, 1.13 to 2.20). The most common first major cardiovascular events were hard coronary disease (8.2%) in men and stroke (5.2%) in women. Type and incidence of first cardiovascular events varied by age and severity of hypertension at onset, with stroke predominating among older subjects with new-onset hypertension. After hypertension onset, cardiovascular events are more likely to occur first as opposed to noncardiovascular death. Types of initial events differ by gender, age, and severity of hypertension at onset. These results represent a novel approach to understanding the complications of hypertension and may help target therapies for patients with new-onset hypertension to optimize prevention strategies. C1 Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. NHLBI, Framingham Heart Study, NIH, Framingham, MA USA. Boston Univ, Sch Med, Div Epidemiol & Prevent Med, Boston, MA 02118 USA. NHLBI, Bethesda, MD 20892 USA. RP Lloyd-Jones, DM (reprint author), Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1120, Chicago, IL 60611 USA. EM dlj@northwestern.edu RI Lloyd-Jones, Donald/C-5899-2009; OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [N01-HC-25195, K23 HL04253] NR 28 TC 27 Z9 28 U1 0 U2 3 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 2005 VL 45 IS 1 BP 39 EP 45 DI 10.1161/01.HYP.0000149106.89470.13 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 883SD UT WOS:000226035100009 PM 15545512 ER PT J AU Hu, Z Wan, HH AF Hu, Z Wan, HH TI A novel generic fast fourier transform pruning technique and complexity analysis SO IEEE TRANSACTIONS ON SIGNAL PROCESSING LA English DT Article DE FFT; number of executed butterflies; pruning ID DISCRETE COSINE TRANSFORM; TIME FFT ALGORITHM; INPUT; COMPUTATION; DFT AB The fast Fourier transform (FFT) is an essential tool in digital signal processing and communications. In the applications of the FFT where the required outputs are very sparse, for example, in digital filtering, one may only require the spectrum corresponding to certain bins of the FFT or in narrow frequency windows. In these cases, most of the FFT outputs are not required. Some pruning algorithms have been proposed to deal with such cases. However, most of the pruning algorithms require that the outputs be in continuous windows. This paper develops a traced FFT Pruning method (TFFTP), which is a novel technique and does not require this condition. Under some circumstances, considerable savings in computational complexity and power consumption can be realized using the TFFTP compared to the FFT. This paper derives the average number of butterflies that need to be executed when only k(in) input or/and k(out) output bins of an N point FFT, where k(in) less than or equal to N, or/and k(out) < N are required. This method is then extended to arbitrary radix FFT pruning and simultaneous input and output pruning case. C1 Maryland Inst Dynamic Genomics, Lab Bioinformat, Silver Spring, MD 20906 USA. IBM Corp, Gaithersburg, MD 20879 USA. NIEHS, Natl Ctr Toxicogenomics, NIH, Res Triangle Pk, NC 27709 USA. RP Hu, Z (reprint author), Maryland Inst Dynamic Genomics, Lab Bioinformat, Silver Spring, MD 20906 USA. EM zhong_h_01@yahoo.com; hwan@niaid.nih.gov NR 23 TC 17 Z9 18 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1053-587X J9 IEEE T SIGNAL PROCES JI IEEE Trans. Signal Process. PD JAN PY 2005 VL 53 IS 1 BP 274 EP 282 DI 10.1109/TSP.2004.838925 PG 9 WC Engineering, Electrical & Electronic SC Engineering GA 880RX UT WOS:000225808000025 ER PT B AU Huang, A Roy, D Franaszek, M Summers, RM AF Huang, A Roy, D Franaszek, M Summers, RM BE Silva, CT Croller, E Rushmeier, H TI Teniae coli guided navigation and registration for virtual colonoscopy SO IEEE VISUALIZATION 2005, PROCEEDINGS LA English DT Proceedings Paper CT IEEE Visualization 2005 Conference CY OCT 23-28, 2005 CL Minneapolis, MN SP IEEE Comp Soc, VGTC, ACM SIGGRAPH DE virtual colonoscopy; CT colonography; virtual endoscopy; camera control; computer-aided diagnosis; colon flattening; parameterization ID COMPUTED-TOMOGRAPHY COLONOGRAPHY; CT COLONOGRAPHY; CENTERLINE; POLYPS AB We present a new method for guiding virtual colonoscopic navigation and registration by using teniae coli as anatomical landmarks. As most existing protocols require a patient to be scanned in both supine and prone positions to increase sensitivity in detecting colonic polyps, reference and registration between scans are necessary. However, the conventional centerline approach, generating only the longitudinal distance along the colon, lacks the necessary orientation information to synchronize the virtual navigation cameras in both scanned positions. In this paper we describe a semi-automatic method to detect teniae coli from a colonic surface model reconstructed from CT colonography. Teniae coli are three bands of longitudinal smooth muscle on the surface of the colon. They form a triple helix structure from the appendix to the sigmoid colon and are ideal references for virtual navigation. Our method was applied to 3 patients resulting in 6 data sets (supine and prone scans). The detected teniae coli matched well with our visual inspection. In addition, we demonstrate that polyps visible on both scans can be located and matched more efficiently with the aid of a teniae coli guided navigation implementation. C1 NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. EM hhuang@cc.nih.gov; dave.roy@gmail.com; mfranaszek@cc.nih.gov; rms@nih.gov NR 20 TC 10 Z9 10 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 BN 0-7803-9462-3 PY 2005 BP 279 EP 285 PG 7 WC Computer Science, Information Systems; Computer Science, Software Engineering; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BDP12 UT WOS:000234666200036 ER PT S AU Yakar, S Pennisi, P Wu, YP Zhao, H LeRoith, D AF Yakar, S Pennisi, P Wu, YP Zhao, H LeRoith, D BE Cianfarani, S Clemmons, DR Savage, MO TI Clinical relevance of systemic and local IGF-I SO IGF-I and IGF Binding Proteins: Basic Research and Clinical Management SE ENDOCRINE DEVELOPMENT LA English DT Proceedings Paper CT Symposium on IGFs and IGFBPs - Assessment and Therapeutic Benefit CY JUN, 2004 CL New Orleans, LA SP Serono Symposia ID GROWTH-FACTOR-I; SOMATOMEDIN AB The insulin-like growth factor family of ligands, receptors and binding proteins are critical for many normal physiological functions. These include normal development during fetal and post-natal development and maintenance of organ function in adult life. Circulating IGF-I is produced primarily by the liver under GH control, whereas the production of tissue IGF-I has other controls. Recent studies have demonstrated that both circulating and tissue IGF-I are important for maintaining the normal structure-function of complex organs such as bone. Circulating IGF-I is important for maintaining ambient GH levels; in its absence GH elevation is seen leading to insulin resistance. In addition, low levels of circulating IGF-I retard the progression and metastatic potential of a number of cancers. (c) Copyright 2005 S. Karger AG, Basel. C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDK, Diabet Branch, NIH, Room 8D12,Bldg 10,MSC 1758, Bethesda, MD 20892 USA. NR 9 TC 39 Z9 41 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1421-7082 BN 3-8055-7926-8 J9 ENDOCRIN DEV PY 2005 VL 9 BP 11 EP 16 DI 10.1159/000085718 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BCO52 UT WOS:000230417400002 PM 15879684 ER PT J AU Brown, P Abee, CR AF Brown, P Abee, CR TI Working with transmissible spongiform encephalopathy agents SO ILAR JOURNAL LA English DT Article DE bovine spongiform encephalopathy; Creutzfeldt-Jakob disease; prion disease; transmissible spongiform encephalopathy AB The family of illnesses called transmissible spongiform encephalopathies (TSEs), or "prion" diseases, is composed of a small number of human and animal neurodegenerative diseases caused by unique pathogenic agents that are still not fully defined. They are best considered as "protein-misfolding diseases" (together with Alzheimer's disease, Parkinson's disease, and a few other rare examples) resulting from the conversion of a normal body protein into a misfolded amyloid multimer. The pathogenic agents display a unique resistance to conventional disinfection methods and an extraordinary environmental durability, which has led the US Department of Agriculture to designate the causative agent of bovine spongiform encephalopathy as a bioterrorism security threat. In this review, precautions and regulations concerning the handling of TSE agents are discussed in relation to personnel and environmental biosafety. C1 Univ S Alabama, Dept Comparat Med, Mobile, AL 36688 USA. RP Brown, P (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 13 TC 4 Z9 5 U1 0 U2 0 PU INST LABORATORY ANIMAL RESEARCH, NATL RES COUNCIL PI WASHINGTON PA 500 FIFTH ST, N W, WASHINGTON, DC 20001 USA SN 1084-2020 J9 ILAR J JI ILAR J. PY 2005 VL 46 IS 1 BP 44 EP 52 PG 9 WC Veterinary Sciences SC Veterinary Sciences GA 892AA UT WOS:000226620900007 PM 15644563 ER PT J AU Weed, JL Raber, JM AF Weed, JL Raber, JM TI Balancing animal research with animal well-being: Establishment of goals and harmonization of approaches SO ILAR JOURNAL LA English DT Article DE animal research; environmental enrichment; experimental design; harmonization; research methods; well-being; welfare ID MEDIATED IMMUNE-RESPONSES; ENVIRONMENTAL ENRICHMENT; RHESUS MACAQUES; NONHUMAN-PRIMATES; FOREIGN-BODY; WELFARE; STRESS; MICE; RATS; BEHAVIOR AB A resource is provided for the creation of an institutional program that balances the scientific mission of an institution with the well-being of the animals used in support of the research. The concept of harmonizing scientific goals with animal well-being was first suggested in the early part of the twentieth century and later revitalized in the literature of the 1950s. Harmonization can best be achieved through the promotion of a team initiative. The team should include, at a minimum, the scientist, veterinarian, institutional animal care and use committee, and animal care staff. It is the responsibility of this animal research team to promote and balance the generation of scientifically valid data with animal wellbeing. The team must strive to minimize or eliminate nonprotocol variables that could adversely affect the validity and repeatability of the experimental data. Good experimental design coupled with excellent communication between team members can often minimize or eliminate many variables and result in both better science and animal wellbeing. To ensure the scientific validity of experimental data, scientists must be aware of the complex nature of the environment in which their animals are maintained. To ensure repeatability of an experiment, scientists must document and publish both the inanimate and social environments in which their animals are housed. Better documentation of environmental variables and their correlation with experimental results will promote critical knowledge about the relationships between an animal's environment, its wellbeing, and science. C1 NIH, Dept Hlth & Human Serv, Div Vet Resources, Bethesda, MD 20892 USA. NIMH, DHHS, NIH, Bethesda, MD 20892 USA. NEI, Bethesda, MD 20892 USA. RP Weed, JL (reprint author), NIH, Dept Hlth & Human Serv, Div Vet Resources, Bethesda, MD 20892 USA. NR 85 TC 23 Z9 23 U1 1 U2 9 PU INST LABORATORY ANIMAL RESEARCH, NATL RES COUNCIL PI WASHINGTON PA 500 FIFTH ST, N W, WASHINGTON, DC 20001 USA SN 1084-2020 J9 ILAR J JI ILAR J. PY 2005 VL 46 IS 2 BP 118 EP 128 PG 11 WC Veterinary Sciences SC Veterinary Sciences GA 901BW UT WOS:000227259000005 PM 15775021 ER PT J AU Hutchinson, E Avery, A VandeWoude, S AF Hutchinson, E Avery, A VandeWoude, S TI Environmental enrichment for laboratory rodents SO ILAR JOURNAL LA English DT Article DE animal husbandry; behavior; environmental enrichment; immunology; rodents; well-being ID MICE MUS-MUSCULUS; NESTING MATERIAL; SYRIAN-HAMSTERS; DBA/2 MICE; RATS; PREFERENCE; MOUSE; BEHAVIOR; WILD; DOMESTICATION AB Modernization of housing and husbandry techniques for rodents has minimized confounding variables. The result has been vastly improved health maintenance and reproducibility of research findings, advances that have decreased the numbers of animals needed to attain statistically significant results. Even though not all aspects of rodent manipulation have been strictly defined, as housing and handling procedures have become increasingly standardized, many animal care personnel have recognized the lack of complexity of the rodents' environment. Concern for this aspect of animal well-being has led many research facilities to provide "environmental enrichment" for rodents. Additionally, regulatory agencies in the United States and Europe have also been increasingly concerned about this issue relative to laboratory animal husbandry. However, little is known about the influence such husbandry modifications may have on biological parameters. In this article, laws and guidelines relating to rodent enrichment are reviewed, the natural behaviors of select rodent species are discussed, and an overview of widely used types of enrichment in laboratory rodent management is provided. The literature evaluating effects of rodent enrichment is reviewed both in terms of neurological development and as an experimental variable, and results of a study evaluating the effect of enrichment on immune and physiological parameters are reported. Survey data on current enrichment practices in a large multi-institutional organization are presented, and practical aspects requiring consideration when devising a rodent enrichment program are discussed. C1 NIH, Dept Hlth & Human Serv, OD ORS, Div Vet Resouces, Bethesda, MD 20892 USA. Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. Colorado State Univ, MIP, Ft Collins, CO 80523 USA. RP Hutchinson, E (reprint author), Colorado State Univ, Coll Vet Med & Biomed Sci, Bethesda, MD USA. NR 71 TC 61 Z9 62 U1 0 U2 22 PU INST LABORATORY ANIMAL RESEARCH, NATL RES COUNCIL PI WASHINGTON PA 500 FIFTH ST, N W, WASHINGTON, DC 20001 USA SN 1084-2020 J9 ILAR J JI ILAR J. PY 2005 VL 46 IS 2 BP 148 EP 161 PG 14 WC Veterinary Sciences SC Veterinary Sciences GA 901BW UT WOS:000227259000008 PM 15775024 ER PT J AU Anderson, AO Shaw, S AF Anderson, AO Shaw, S TI Conduit for privileged communications in the lymph node SO IMMUNITY LA English DT Editorial Material ID CD4 T-CELLS; DENDRITIC CELLS; ANTIGEN; CORTEX; ENCOUNTER AB A study by Sixt et al. in this issue of Immunity identifies conduit-associated dendritic cells whose privileged access to antigen arriving by the conduit enables uptake and processing of antigen within 90 min of antigen inoculation, long before the arrival of dendritic cells from skin. C1 USA, Med Res Inst Infect Dis, Dept Clin Pathol, Frederick, MD 21702 USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Anderson, AO (reprint author), USA, Med Res Inst Infect Dis, Dept Clin Pathol, Frederick, MD 21702 USA. NR 11 TC 24 Z9 25 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 2005 VL 22 IS 1 BP 3 EP 5 DI 10.1016/j.immuni.2005.01.003 PG 3 WC Immunology SC Immunology GA 892XI UT WOS:000226682900001 PM 15664153 ER PT J AU Grivennikov, SI Tumanov, AV Liepinsh, DJ Kruglov, AA Marakusha, BI Shakhov, AN Murakami, T Drutskaya, LN Forster, I Clausen, BE Tessarollo, L Ryffel, B Kuprash, DV Nedospasov, SA AF Grivennikov, SI Tumanov, AV Liepinsh, DJ Kruglov, AA Marakusha, BI Shakhov, AN Murakami, T Drutskaya, LN Forster, I Clausen, BE Tessarollo, L Ryffel, B Kuprash, DV Nedospasov, SA TI Distinct and nonredundant in vivo functions of TNF produced by T cells and macrophages/neutrophils: Protective and deleterious effects SO IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INFLAMMATORY-BOWEL-DISEASE; INDUCED LETHAL SHOCK; RHEUMATOID-ARTHRITIS; LISTERIA-MONOCYTOGENES; FACTOR RECEPTOR; LIVER-INJURY; B-CELLS; MYCOBACTERIUM-TUBERCULOSIS; LYMPHOTOXIN-ALPHA AB Tumor necrosis factor (TNF, TNFalpha) is implicated in various pathophysiological processes and can be either protective, as in host defense, or deleterious, as in autoimmunity or toxic shock. To uncover the in vivo functions of TNF produced by different cell types, we generated mice with TNF ablation targeted to various leukocyte subsets. Systemic TNF in response to lipopolysaccharide was produced mainly by macrophages and neutrophils. This source of TNF was indispensable for resistance to an intracellular pathogen, Listeria, whereas T-cell-derived TNF was important for protection against high bacterial load. Additionally, both T-cell-derived TNF and macrophage-derived TNF had critical and nonredundant functions in the promotion of autoimmune hepatitis. Our data suggest that T-cell-specific TNF ablation may provide a therapeutic advantage over systemic blockade. C1 Russian Acad Sci, VA Engelhardt Mol Biol Inst, Lab Mol Immunol, Moscow 119991, Russia. Belozersky Inst Physicochem Biol, Moscow 119991, Russia. NCI, Canc Res Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NCI, Canc Res Ctr, Mouse Genet Program, Frederick, MD 21702 USA. SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. Russian Acad Med Sci, Gamaleya Inst Epidemiol & Microbiol, Moscow 123098, Russia. Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-81675 Munich, Germany. Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands. CNRS, Inst Transgenose, IEM, F-45071 Orleans, France. RP Nedospasov, SA (reprint author), Russian Acad Sci, VA Engelhardt Mol Biol Inst, Lab Mol Immunol, 32 Vavilov Str, Moscow 119991, Russia. EM snedos@online.ru RI CLAUSEN, Bjorn/A-8229-2010; Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Forster, Irmgard/P-8545-2016; Nedospasov, Sergei/Q-7319-2016; OI CLAUSEN, Bjorn/0000-0002-2484-7842; Kuprash, Dmitry/0000-0002-1488-4148; kruglov, andrey/0000-0002-4597-2087 NR 57 TC 158 Z9 167 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 2005 VL 22 IS 1 BP 93 EP 104 DI 10.1016/j.immuni.2004.11.016 PG 12 WC Immunology SC Immunology GA 892XI UT WOS:000226682900010 PM 15664162 ER PT J AU Rezanka, LJ Kenny, JJ Longo, DL AF Rezanka, LJ Kenny, JJ Longo, DL TI 2 BCR or NOT 2 BCR - Receptor dilution: a unique mechanism for preventing the development of holes in the protective B cell repertoire SO IMMUNOBIOLOGY LA English DT Article; Proceedings Paper CT 2nd Tutzing Antiphospholipid Conference CY APR 18-21, 2005 CL Tutzing, GERMANY ID IMMUNE-DEFICIENT MICE; IMMUNOGLOBULIN LIGHT-CHAINS; REACTIVE LYMPHOCYTES-B; STREPTOCOCCUS-PNEUMONIAE; BONE-MARROW; ANTIBODY REPERTOIRE; GENE REARRANGEMENT; ALLELIC EXCLUSION; CLONAL DELETION; TRANSGENIC MICE AB The clonal selection theory and the associated corollaries have had a major influence in shaping our thinking about lymphoid cell development as well as how these cells respond to antigenic challenges. Among these concepts are that a single B cell expresses a single receptor with a single antigen specificity. While these hypotheses have proven invaluable in expanding our understanding of immune response, over time numerous observations have been made that suggest that the single cell, single receptor, single specificity model is not absolute. In this manuscript, we review this literature as it pertains to B cells and provide a summary that supports the notion that in certain situations, the overarching rules by which we consider development and response of immune cells may be compromised. The result of compromising allelic and isotype exclusion is a small but real population of dual receptor expressing B cells. A number of mechanisms that have been proposed for generating these dual expressing B cells are presented and discussed. We also consider the negative implications of dual receptor expression on regulating and controlling autoreactive B cell populations as well as its beneficial contributions to preserving essential receptor specificities and thereby preventing the development of holes in the immune repertoire. Previously, the dual receptor expressing population has received relatively little attention. Improvements in the tools available to examine individual B cell populations have resulted in our identification of and discrimination between novel populations of B cells, including novel dual receptor expressing populations. This combined with continuing increases in our understanding of how the immune repertoire relates to a protective immune response will strengthen and further define this novel aspect of immune cell development. (C) 2005 Elsevier GmbH. All rights reserved. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Rezanka, LJ (reprint author), NIA, Immunol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rezankal@grc.nia.nih.gov NR 71 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PY 2005 VL 210 IS 10 BP 769 EP 774 DI 10.1016/j.imbio.2005.10.008 PG 6 WC Immunology SC Immunology GA 994RV UT WOS:000234049800008 PM 16325496 ER PT J AU Beck, TW Menninger, J Murphy, WJ Nash, WG O'Brien, SJ Yuhki, N AF Beck, TW Menninger, J Murphy, WJ Nash, WG O'Brien, SJ Yuhki, N TI The feline major histocompatibility complex is rearranged by an inversion with a breakpoint in the distal class I region SO IMMUNOGENETICS LA English DT Article ID RADIATION HYBRID MAP; COMPARATIVE GENOME ORGANIZATION; SEQUENCING ANALYSIS; SATELLITE DNA; CONTIG MAP; BAC CONTIG; MHC GENES; EVOLUTION; CATTLE; LOCALIZATION AB In order to determine the genomic organization of the major histocompatibility complex (MHC) of the domestic cat ( Felis catus), DNA probes for 61 markers were designed from human MHC reference sequences and used to construct feline MHC BAC contig map spanning ARE1 in the class II region to the olfactory receptor complex in the extended class I region. Selected BAC clones were then used to identify feline-specific probes for the three regions of the mammalian MHC ( class II - class III - class I) for radiation hybrid mapping and fluorescent in situ hybridization to refine the organization of the domestic cat MHC. The results not only confirmed that the p-arm of domestic cat B2 is inverted relative to human Chromosome 6, but also demonstrated that one inversion breakpoint localized to the distal segment of the MHC class I between TRIM39 and TRIM26. The inversion thus disjoined the similar to 2.85 Mb of MHC containing class II - class III - class I ( proximal region) from the similar to 0.50 Mb of MHC class I/extended class I region, such that TRIM39 is adjacent to the Chromosome B2 centromere and TRIM26 is adjacent to the B2 telomere in the domestic cat. C1 NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. H&W Cytogenet Serv, Lovettsville, VA 20180 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Yuhki, N (reprint author), NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. EM yuhki@ncifcrf.gov FU PHS HHS [N01-C0-12400] NR 57 TC 18 Z9 18 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD JAN PY 2005 VL 56 IS 10 BP 702 EP 709 DI 10.1007/s00251-004-0742-6 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 889TP UT WOS:000226465800003 PM 15592824 ER PT J AU Iribarren, P Zhou, Y Hu, JY Le, YY Wang, JM AF Iribarren, P Zhou, Y Hu, JY Le, YY Wang, JM TI Role of formyl peptide receptor-like 1 (FPRL1/FPR2) in mononuclear phagocyte responses in Alzheimer disease SO IMMUNOLOGIC RESEARCH LA English DT Article DE Alzheimer disease; amyloid beta; formyl peptide receptor; inflammation ID MURINE MICROGLIAL CELLS; AMYLOID-BETA-PROTEIN; FORMYL PEPTIDE RECEPTOR; METHIONYL-LEUCYL-PHENYLALANINE; NITRIC-OXIDE SYNTHASE; BLOOD-BRAIN-BARRIER; A-BETA; GENE-EXPRESSION; UP-REGULATION; IN-VIVO AB Alzheimer disease (AD) is the most common neurodegenerative disease. affecting approx 4 million people in the United States in the year 2000 alone. Amyloid β (Aβ) deposition, activated glial cells, and neuritic degeneration are the characteristic features of AD. Although the precise cause of AD has yet to be determined, a bulk of evidence suggests that inflammatory responses elicited by elevated Aβ peptides play an important role in the pathogenic process of the disease. In AD brain, mononuclear phagocytes (microglia) accumulate at the sites of Aβ peptide deposition. In vitro, Aβ peptides activate mononuclear phagocytes to release neurotoxic mediators. A number of cell-surface molecules have been reported to act as putative receptors for Aβ peptides, among which the G protein-coupled formyl peptide receptor-like 1 (FPRL1) and its mouse homolog FPR2 have been shown to be expressed by activated microglial cells and mediate the chemotactic activity of the 42 amino acid form of Aβ (Aβ 42). FPRL1 also participates in Aβ 42 internalization in macrophages and its cytotoxicity for neuronal cells. Therefore, FPRL1 may be involved in the inflammatory aspects of AD. This review discusses recent findings relevant to the function and regulation of FPRL1/FPR2 in mononuclear phagocytes by pro- and antiinflammatory signals and its potential as a therapeutic target in AD. C1 NCI, Ctr Canc Res, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai, Peoples R China. RP Wang, JM (reprint author), NCI, Ctr Canc Res, Mol Immunoregulat Lab, Bldg 560,Room 31-40, Frederick, MD 21702 USA. EM wangji@mail.ncifcrf.gov FU NCI NIH HHS [N01 CO 56000] NR 96 TC 46 Z9 47 U1 0 U2 4 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 2005 VL 31 IS 3 BP 165 EP 176 DI 10.1385/IR:31:3:165 PG 12 WC Immunology SC Immunology GA 924MF UT WOS:000228982200001 PM 15888909 ER PT J AU Yoshimura, T Matsuyama, W Kamohara, H AF Yoshimura, T Matsuyama, W Kamohara, H TI Discoidin domain receptor 1 - A new class of receptor regulating leukocyte-collagen interaction SO IMMUNOLOGIC RESEARCH LA English DT Article DE collagen; discoidin domain receptor 1; macrophages; dendritic cells; cell signaling; cell migration; cell differentiation ID ACTIVATED PROTEIN-KINASE; NF-KAPPA-B; TYROSINE KINASE; DENDRITIC CELLS; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; MATURATION; LIPOPOLYSACCHARIDE; MACROPHAGES; TAK1 AB Previous Studies demonstrated that type I collagen, a major component of the extracellular matrix, could influence the differentiation and function of leukocytes; however, it is not clear whether those effects of colla-en were based on its interaction with the classic collagen receptors, α 1β 1 and α 2β 1 integrins. We recently detected significant Upregulation of discoidin domain receptor 1 (DDR1), a new class of collagen receptor, in human leukocytes, including neutrophils, monocytes, and lymphocytes, in vitro, leading, to the hypothesis that the leukocyte-activating effects of collagen might be owing to its interaction with DDR1. In this review, we summarize Our recent findings demonstrating that DDR1-collagen interaction facilitates the adhesion, migration, differentiation/maturation, and cytokine/chemokine production of leukocytes. We also describe the intracellular signaling pathways activated by DDR1 interaction with collagen. C1 NCI, Ctr Canc Res, Lab Mol Immunoregulat, Frederick, MD 21702 USA. RP Yoshimura, T (reprint author), NCI, Ctr Canc Res, Lab Mol Immunoregulat, Bldg 599,Room 9, Frederick, MD 21702 USA. EM yoshimur@mail.ncifcrf.gov NR 50 TC 26 Z9 26 U1 0 U2 2 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 2005 VL 31 IS 3 BP 219 EP 229 DI 10.1385/IR:31:3:219 PG 11 WC Immunology SC Immunology GA 924MF UT WOS:000228982200005 PM 15888913 ER PT J AU Punareewattana, K Gogal, RM Sharova, LV Ward, DL Holladay, SD AF Punareewattana, K Gogal, RM Sharova, LV Ward, DL Holladay, SD TI Reduced birth defects caused by maternal immune stimulation in diabetic ICR mice: Lack of correlation with placental gene expression SO IMMUNOLOGICAL INVESTIGATIONS LA English DT Article DE diabetes; diabetic embryopathy; teratogenesis; birth defects; IFN-gamma; GM-CSF; Freund's adjuvant; gene array ID PROTEIN-KINASE-C; GROWTH-FACTOR; MURINE MACROPHAGES; FETAL DEVELOPMENT; UTERUS; RAT; DIFFERENTIATION; PREGNANCY; MELLITUS; MUSCLE AB Diabetes mellitus alters placental structure and function, events that may be related to embryopathy. Three different methods of maternal immune stimulation that modulate placental function and that result in approximately equal reduction of diabetic embryopathy were studied: footpad injection with complete Freund's adjuvant, intraperitoneal injection with granulocyte-macrophage colony stimulating factor (GM-CSF), or intraperitoneal injection with interferon-gamma (IFN-gamma). A gene microarray was then used to examine expression of 151 placental genes. We hypothesized that maternal immune stimulation may overcome an embryopathy-inducing effect of diabetes on placenta, that might be detected by a shared profile of placental gene expression changes induced by the different immune stimulation procedures. However, the immune stimulation that caused the greatest reduction in birth defect incidence, IFN-gamma, did not change the placental gene expression profile as compared to control or diabetes. Complete Freund's adjuvant and GM-CSF significantly changed placental gene expression relative to control or diabetes, but differentially affected such genes. No common pattern of improved cytokine, cell-cycle, apoptotic, transcription factor, or other gene expression was identified, that might explain the ability of this procedure to reduce birth defects. These data suggest that maternal immune stimulation reduces birth defects in diabetic mice by a mechanism independent of placenta. C1 Virginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA. NIA, Genet Lab, Baltimore, MD 21224 USA. Virginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Off Grad Studies, Blacksburg, VA 24061 USA. Virginia Coll Osteopath Med, Blacksburg, VA USA. RP Holladay, SD (reprint author), Virginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA. EM holladay@vt.edu NR 36 TC 1 Z9 3 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0882-0139 J9 IMMUNOL INVEST JI Immunol. Invest. PY 2005 VL 34 IS 1 BP 71 EP 89 DI 10.1081/1MM-200047389 PG 19 WC Immunology SC Immunology GA 902QP UT WOS:000227371900005 PM 15773573 ER PT J AU Krakauer, T Chen, X Howard, OMZ Young, HA AF Krakauer, T Chen, X Howard, OMZ Young, HA TI Triptolide attenuates endotoxin- and staphylococcal exotoxin-induced T-cell proliferation and production of cytokines and chemokines SO IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY LA English DT Article DE cytokine; SEB; TSST-1; LPS; immunosuppression; triptolide ID WILFORDII HOOK-F; TOXIC-SHOCK-SYNDROME; TUMOR-NECROSIS-FACTOR; TRIPTERYGIUM-WILFORDII; ALLOGRAFT SURVIVAL; EPITHELIAL-CELLS; GENE-EXPRESSION; HUMAN-DISEASE; SUPERANTIGENS; ACTIVATION AB Proinflammatory cytokines mediate the toxic effects of superantigenic staphylococcal exotoxins (SE) and bacterial lipopolysaccharide (LPS). Triptolide, an oxygenated diterpene derived from a traditional Chinese medicinal herb, Tripterygium wilfordii, inhibited SE-stimulated T-cell proliferation (by 98%) and expression of interleukin 1 beta, interleukin 6, tumor necrosis factor, gamma interferon, monocyte chemotactic protein 1, macrophage inflammatory protein (MIP)-1 alpha, and MIP-1 beta by human peripheral blood mononuclear cells (PBMC). It also blocked the production of these cytokines and chemokines by LPS-stimulated PBMC in a dose-dependent manner. These results suggest that triptolide has potent immunosuppressive effects even counteracting the effects of superantigens and LPS. It also may be therapeutically useful for mitigating the pathogenic effects of these microbial products by downregulating the signaling pathways activated by both bacterial exotoxins and endotoxins. C1 USA, Med Res Inst Infect Dis, Dept Immunol & Mol Biol, Frederick, MD 21702 USA. NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Natl Canc Inst, Expt Immunol Lab, Canc Res Ctr, Frederick, MD USA. RP Krakauer, T (reprint author), USA, Med Res Inst Infect Dis, Dept Immunol & Mol Biol, Bldg 1425, Frederick, MD 21702 USA. EM Teresa.Krakauer@det.amedd.army.mil RI Young, Howard/A-6350-2008; Howard, O M Zack/B-6117-2012; Chen, Xin/I-6601-2015 OI Young, Howard/0000-0002-3118-5111; Howard, O M Zack/0000-0002-0505-7052; Chen, Xin/0000-0002-2628-4027 NR 37 TC 28 Z9 32 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0892-3973 J9 IMMUNOPHARM IMMUNOT JI Immunopharmacol. Immunotoxicol. PY 2005 VL 27 IS 1 BP 53 EP 66 DI 10.1081/IPH-200051294 PG 14 WC Immunology; Pharmacology & Pharmacy; Toxicology SC Immunology; Pharmacology & Pharmacy; Toxicology GA 910NY UT WOS:000227939800004 PM 15803859 ER PT J AU Bornstein, MH Cote, LR AF Bornstein, MH Cote, LR TI Expressive vocabulary in language learners from two ecological settings in three language communities SO INFANCY LA English DT Article; Proceedings Paper CT 18th Biennial Meeting of the International-Society-for-the-Study-of-Behavioral-Development CY JUL 11-15, 2004 CL Ghent, BELGIUM SP Int Soc Study Behav Dev ID EARLY LEXICAL DEVELOPMENT; SEX-DIFFERENCES; YOUNG-CHILDREN; ENGLISH; GENDER; COMPETENCE; CONTINUITY; MANDARIN; CONTEXT; SPANISH AB This study compared multiple characteristics of girls'and boys'vocabulary in 6 different linguistic communities-1 urban and 1 rural setting in each of 3 countries. Two hundred fifty-two mothers in Argentina, Italy, and the United States completed vocabulary checklists for their 20-month-old children. Individual variability was substantial within each linguistic community. Minimal cross-linguistic differences were found in children's vocabulary size; however, differences among languages in the composition of children's vocabularies appeared possibly related to cultural valuing of different categories of words. Ecological setting differences within cultures appeared in children's vocabulary size, even when the composition of children's vocabularies was examined: Children living in urban areas were reported by their mothers to say significantly more words than children living in rural areas, particularly for Argentine and U. S. children. Girls had consistently larger vocabularies than boys. These findings are discussed in terms of contextual and child factors that together influence first language learning. C1 Natl Inst Child Hlth & Human Dev, Child & Family Res, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), Natl Inst Child Hlth & Human Dev, Child & Family Res, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov NR 65 TC 10 Z9 10 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1525-0008 J9 INFANCY JI Infancy PY 2005 VL 7 IS 3 BP 299 EP 316 DI 10.1207/s15327078in0703_5 PG 18 WC Psychology, Developmental SC Psychology GA 951PA UT WOS:000230941600005 ER PT J AU Darko, CA Angov, E Collins, WE Bergmann-Leitner, ES Girouard, AS Hitt, SL McBride, JS Diggs, CL Holder, AA Long, CA Barnwell, JW Lyon, JA AF Darko, CA Angov, E Collins, WE Bergmann-Leitner, ES Girouard, AS Hitt, SL McBride, JS Diggs, CL Holder, AA Long, CA Barnwell, JW Lyon, JA TI The clinical-grade 42-kilodalton fragment of merozoite surface protein 1 of Plasmodium falciparum strain FVO expressed in Escherichia coli protects Aotus nancymai against challenge with homologous erythrocytic-stage parasites SO INFECTION AND IMMUNITY LA English DT Article ID C-TERMINAL FRAGMENT; MALARIA VACCINE DEVELOPMENT; MONOCLONAL-ANTIBODY; IN-VITRO; CRITICAL PATH; MONKEYS; INVASION; INHIBIT; GROWTH; IMMUNIZATION AB A 42-kDa fragment from the C terminus of major merozoite surface protein 1 (MSPI) is among the leading malaria vaccine candidates that target infection by asexual erythrocytic-stage malaria parasites. The MSP1(42) gene fragment from the Vietnam-Oak Knoll (FVO) strain of Plasmodium falciparum was expressed as a soluble protein in Escherichia coli and purified according to good manufacturing practices. This clinical-grade recombinant protein retained some important elements of correct structure, as it was reactive with several functional, conformation-dependent monoclonal antibodies raised against P. falciparum malaria parasites, it induced antibodies (Abs) that were reactive to parasites in immunofluorescent Ab tests, and it induced strong growth and invasion inhibitory antisera in New Zealand White rabbits. The antigen quality was further evaluated by vaccinating Aotus naneymai monkeys and challenging them with homologous P. falciparum FVO erythrocytic-stage malaria parasites. The trial included two control groups, one vaccinated with the sexual-stage-specific antigen of Plasmodium vivax, Pvs25, as a negative control, and the other vaccinated with baculovirus-expressed MSPI,, (FVO) as a positive control. Enzyme-linked immunosorbent assay (ELISA) Ab titers induced by E. coli MSP1(42) were significantly higher than those induced by the baculovirus-expressed antigen. None of the six monkeys that were vaccinated with the E. coli MSPI,, antigen required treatment for uncontrolled parasitemia, but two required treatment for anemia. Protective immunity in these monkeys correlated with the ELISA Ab titer against the p19 fragment and the epidermal growth factor (EGF)-like domain 2 fragment of MSP1(42), but not the MSP1(42) protein itself or the EGF-like domain 1 fragment. Soluble MSP1(42) (FVO) expressed in E. coli offers excellent promise as a component of a vaccine against erythrocytic-stage falciparum malaria. C1 Walter Reed Army Inst Res, Dept Immunol, Silver Spring, MD 20910 USA. NIAID, Malaria Vaccine Dev Unit, NIH, Rockville, MD USA. Ctr Dis Control & Prevent, Div Parasit Dis, Chamblee, GA USA. US Agcy Int Dev, USAID Malaria Vaccine Dev Program, Washington, DC 20523 USA. Univ Edinburgh, Sch Biol Sci, Edinburgh EH8 9YL, Midlothian, Scotland. Natl Inst Med Res, Div Parasitol, London NW7 1AA, England. RP Angov, E (reprint author), Walter Reed Army Inst Res, Dept Immunol, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. EM Evelina.angov@na.amedd.army.mil RI Bergmann-Leitner, Elke/B-3548-2011; Holder, Anthony/A-7554-2013 OI Bergmann-Leitner, Elke/0000-0002-8571-8956; Holder, Anthony/0000-0002-8490-6058 FU Medical Research Council [MC_U117532067]; NIAID NIH HHS [YIAI-0438-03]; NIDCD NIH HHS [CDC C100-042] NR 41 TC 80 Z9 82 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2005 VL 73 IS 1 BP 287 EP 297 DI 10.1128/IAI.73.1.287-297.2004 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 883TD UT WOS:000226037700029 PM 15618165 ER PT J AU Khan, AQ Chen, QY Wu, ZQ Paton, JC Snapper, CM AF Khan, AQ Chen, QY Wu, ZQ Paton, JC Snapper, CM TI Both innate immunity and type 1 humoral immunity to Streptococcus pneumoniae are mediated by MyD88 but differ in their relative levels of dependence on Toll-like receptor 2 SO INFECTION AND IMMUNITY LA English DT Article ID RESPONSES IN-VIVO; PLASMACYTOID DENDRITIC CELLS; HELPER T-CELLS; CUTTING EDGE; MYD88-DEFICIENT MICE; ISOTYPE RESPONSES; BORRELIA-BURGDORFERI; DISTINCT MECHANISMS; WALL COMPONENTS; BACTERIAL AB Little is known regarding the role of Toll-like receptors (TLRs) in regulating protein- and polysaccharide-specific immunoglobulin (Ig) isotype production in response to an in vivo challenge with an extracellular bacterium. In this report we demonstrate that MyD88(-/-), but not TLR2(-/-), mice are markedly defective in their induction of multiple splenic proinflammatory cytokine- and chemokine-specific mRNAs after intraperitoneal (i.p.) challenge with heat-killed Streptococcus pneumoniae capsular type 14 (S. pneumoniae type 14). This is correlated with analogous responses in splenic cytokine protein release in vitro following addition of S. pneumoniae type 14. Consistent with these data, naive MyD88-/-, but not TLR2-/-, mice are more sensitive to killing following i.p. challenge with live S. pneumoniae type 14, relative to responses in wild-type mice. However, prior immunization of MyD88-/- mice with heat-killed S. pneumoniae type 14 protects against an otherwise-lethal challenge with live S. pneumoniae type 14. Surprisingly, both MyD88-/- and TLR2-/- mice exhibit striking and equivalent defects in elicitation of type 1 IgG isotypes (IgG3, IgG2b, and IgG2a), but not the type 2 IgG isotype, IgG1, specific for several protein and polysaccharide antigens, in response to i.p. challenge with heat-killed S. pneumoniae type 14. Of note, the type I IgG isotype titers specific for pneumococcal surface protein A are reduced in MyD88-/- mice but not TLR2-/- mice. These data suggest that distinct TLRs may differentially regulate innate versus adaptive humoral immunity to intact S. pneumoniae and are the first to implicate a role for TLR2 in shaping an in vivo type I IgG humoral immune response to a gram-positive extracellular bacterium. C1 Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. Univ Adelaide, Sch Mol & Biomed Sci, Adelaide, SA 5005, Australia. RP Snapper, CM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pathol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM csnapper@usuhs.mil RI Paton, James/A-9920-2008 FU NIAID NIH HHS [1R01 AI46551, 1R01 AI49192, R01 AI046551, R01 AI049192] NR 58 TC 75 Z9 76 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2005 VL 73 IS 1 BP 298 EP 307 DI 10.1128/IAI.73.1.298-307.2005 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 883TD UT WOS:000226037700030 PM 15618166 ER PT J AU Kim, MP Gaydos, CA Wood, BJ Hardick, JP Zhang, YH Wahl, LM AF Kim, MP Gaydos, CA Wood, BJ Hardick, JP Zhang, YH Wahl, LM TI Chlamydia pneumoniae enhances cytokine-stimulated human monocyte matrix metalloproteinases through a prostaglandin E-2-Dependent mechanism SO INFECTION AND IMMUNITY LA English DT Article ID CORONARY HEART-DISEASE; MACROPHAGES; INFECTION; EXPRESSION; ARTERIES; LESIONS; ALPHA; CELLS; TWAR AB Exposure of human monocytes to Chlamydia pneumoniae resulted in a significant enhancement of matrix metalloproteinase (MMP) 1 and 9 production following stimulation with tumor necrosis factor alpha and granulocyte monocyte-colony stimulating factor. The effect of C pneumoniae on monocyte MMPs was mediated through the induction of prostaglandin E, These findings may have implications for atherosclerotic plaque rupture. C1 Natl Inst Dent & Craniofacial Res, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. RP Wahl, LM (reprint author), Natl Inst Dent & Craniofacial Res, Immunopathol Sect, NIH, 30 Convent Dr,Bldg 30,Room 325, Bethesda, MD 20892 USA. EM lwahl@dir.nidcr.nih.gov RI Gaydos, Charlotte/E-9937-2010 NR 17 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2005 VL 73 IS 1 BP 632 EP 634 DI 10.1128/IAI.73.1.632-634.2005 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 883TD UT WOS:000226037700070 PM 15618206 ER PT J AU Boirivant, M Strober, W Fuss, IJ AF Boirivant, M Strober, W Fuss, IJ TI Regulatory cells induced by feeding TNP-Haptenated colonic protein cross-protect mice from colitis induced by an unrelated hapten SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE colitis; regulatory cells; tolerance ID INFLAMMATORY-BOWEL-DISEASE; ORAL TOLERANCE; T-CELLS; TGF-BETA AB In previous studies, we have shown that the oral administration of colonic proteins that have been haptenated (i.e., haptenated colonic proteins [HCPs]) with trinitrophenol (TNP) can protect mice from the subsequent induction of trinitrobenzene sulfonic acid colitis. Inasmuch as this protection was mediated by regulatory cells that express the antigen-non-specific suppressor factors transforming growth factor-beta and interleukin-10, we reasoned that TNP-HCP feeding would also "cross-protect" mice from colitis induced by a different hapten, oxazolone. Indeed, we found that feeding TNP-HCP protected mice from the development of oxazolone-colitis, albeit to a lesser extent than it protected mice from trinitrobenzene sulfonic acid colitis. In addition, we showed that protection was associated with the appearance of mononuclear cells producing regulatory cytokines. These data strongly imply that the cells induced by feeding 1 type of haptenated protein are capable of cross-reacting with antigens present in colitis produced by a second type of haptenated protein. The crossprotection demonstrated in this study holds promise for the treatment of humans with inflammatory bowel disease because it shows that an appropriate fed antigen can induce regulatory cells that have the potential to suppress an inflammation induced by the unknown antigens causing this disease. C1 Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, I-00161 Rome, Italy. NIAID, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA. RP Boirivant, M (reprint author), Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, Viale Regina Elena 299, I-00161 Rome, Italy. EM monboir@iss.it RI BOIRIVANT, MONICA/B-9977-2016 NR 12 TC 6 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JAN PY 2005 VL 11 IS 1 BP 48 EP 55 DI 10.1097/00054725-200501000-00007 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 884CG UT WOS:000226061600007 PM 15674113 ER PT S AU Kasabov, NK Chan, ZKSH Jain, V Sidorov, I Dimitrov, DS AF Kasabov, Nikola K. Chan, Zeke S. H. Jain, Vishal Sidorov, Igor Dimitrov, Dimiter S. BE Bajic, VB Wee, TT TI COMPUTATIONAL MODELLING OF GENE REGULATORY NETWORKS SO INFORMATION PROCESSING AND LIVING SYSTEMS SE Series on Advances in Bioinformatics and Computational Biology LA English DT Article; Book Chapter ID FUNCTIONAL GENOMICS; EXPRESSION PATTERNS; CELL-CYCLE AB Major cell functions are dependent on interactions between DNA, RNA and proteins. Directly or indirectly in a cell such molecules either interact in a positive or in repressive manner and such interplay leads to genetic regulatory networks (GRN) which in turn controls the gene regulation. Therefore it is hard to obtain the accurate computational models through which the final state of a cell can be predicted with certain accuracy and it can help scientific community to better understand the functioning of organism. Here we summarize the biological behavior of actual regulatory systems and have made an attempt for GRN discovery of a large number of genes from multiple time series gene expression observations over small and irregular time intervals. The method integrates a genetic algorithm (GA) to select a small number of genes and a Kalman filter to derive the GRN of these genes. After GRNs of smaller number of genes are obtained, these GRNs may be integrated in order to create the GRN of a larger group of genes of interest. C1 [Kasabov, Nikola K.; Chan, Zeke S. H.; Jain, Vishal] Auckland Univ Technol, KEDRI, Auckland, New Zealand. [Sidorov, Igor; Dimitrov, Dimiter S.] NCI, NIH, Bethesda, MD 20892 USA. RP Kasabov, NK (reprint author), Auckland Univ Technol, KEDRI, Auckland, New Zealand. EM nkasabov@aut.ac.nz; shchan@aut.ac.nz; vishal.jain@aut.ac.nz; sidorovi@ncifcrf.gov; dimitrov@ncifcrf.gov RI Tan, Tin Wee/B-8963-2009 OI Tan, Tin Wee/0000-0002-4062-2854 NR 33 TC 2 Z9 2 U1 0 U2 0 PU IMPERIAL COLLEGE PRESS PI COVENT GARDEN PA 57 SHELTON STREET, COVENT GARDEN WC2H 9HE, ENGLAND SN 1751-6404 BN 978-1-86094-688-2 J9 SER ADV BIOINFORM PY 2005 VL 2 BP 673 EP 686 PG 14 WC Mathematical & Computational Biology; History & Philosophy Of Science SC Mathematical & Computational Biology; History & Philosophy of Science GA BYR90 UT WOS:000299925400009 ER PT J AU Dinglasan, RR Valenzuela, JG Azad, AF AF Dinglasan, RR Valenzuela, JG Azad, AF TI Sugar epitopes as potential universal disease transmission blocking targets SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE carbohydrate; transmission blocking vaccine; mosquito; midget; vector-borne disease ID ANOPHELES-STEPHENSI; AEDES-AEGYPTI; SACCHARIDE-BINDING; CONCANAVALIN-A; JACALIN; MIDGUT; MOSQUITO; MALARIA; LECTIN; CELLS AB One promising method to prevent vector-borne diseases is through the use of transmission blocking vaccines (TBVs). However, developing several anti-pathogen TBVs may be impractical. In this study, we have identified a conserved candidate carbohydrate target in the midguts of several Arthropod vectors. A screen of the novel GlycoChip(R) glycan array found that the anti-carbohydrate malaria transmission blocking monoclonal antibody (MG96) preferentially recognized D-mannose (a) and the type 11 lactosamine disaccharide. The specificity for D-mannose was confirmed by competition ELISA using alpha-methyl mannoside as inhibitor. Con A, which identifies terminal mannose residues, did not inhibit MG96 reactivity with mosquito midgut lysates, suggesting that Con A has differential recognition of this monosaccharide. However, the jack bean lectin, Jacalin, which recognizes D-mannose (alpha), D-galactose (alpha/beta) and the T antigen, not only displays a similar banding profile to that recognized by MG96 on immunoblot but was also shown to effectively inhibit MG96. Wheat-germ agglutinin, which recognizes N-acetyllactosamine units, only partially inhibited MG96 reactivity. This highlights the contribution of both glycan moieties to the MG96 epitope or glycotope. Enzyme deglycosylation results suggest that MG96 recognizes a mannose alpha1-6 substitution on an O-linked oligosaccharide. Taken together, the data suggest that MG96 recognizes a discontinuous glycotope composed of Manalpha1-6 proximal to Galbeta1-4GlcNAc-alpha-O-R glycans on arthropod vector midguts. As such, these glycotopes may represent potential transmission blocking vaccine targets for a wide range of vector-borne pathogens. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Dinglasan, RR (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, 615 N Wolfe St,Room W4109, Baltimore, MD 21205 USA. EM rdinglas@jhsph.edu; jvalenzuela@nih.gov; aazad@umaryland.edu OI Dinglasan, Rhoel/0000-0001-5433-8179; Dinglasan, Rhoel/0000-0001-6563-1506 NR 38 TC 36 Z9 39 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD JAN PY 2005 VL 35 IS 1 BP 1 EP 10 DI 10.1016/j.ibmb.2004.09.005 PG 10 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 888VQ UT WOS:000226402700001 PM 15607650 ER PT J AU Conrads, TP Issaq, HJ Blonder, JS Veenstra, TD AF Conrads, Thomas P. Issaq, Haleem J. Blonder, Josip S. Veenstra, Timothy D. BA Lee, MS BF Lee, MS TI MASS SPECTROMETRY-BASED PROTEOMIC APPROACHES FOR DISEASE DIAGNOSIS AND BIOMARKER DISCOVERY SO INTEGRATED STRATEGIES FOR DRUG DISCOVERY USING MASS SPECTROMETRY LA English DT Article; Book Chapter ID PROTEIN BIOCHIP TECHNOLOGY; HUMAN PLASMA PROTEOME; OVARIAN-CANCER; ELECTROPHORESIS; ADENOCARCINOMA; IDENTIFICATION; CAPTURE; SERUM C1 [Conrads, Thomas P.; Veenstra, Timothy D.] NCI, Biomed Prote Program, SAIC Frederick, Frederick, MD 21702 USA. RP Conrads, TP (reprint author), NCI, Biomed Prote Program, SAIC Frederick, Frederick, MD 21702 USA. NR 32 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-471-72103-1 PY 2005 BP 95 EP 120 DI 10.1002/0471721034.ch4 D2 10.1002/0471721034 PG 26 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BYA67 UT WOS:000297763900005 ER PT J AU Bi, XL Yang, JY Dong, YX Wang, JM Cui, YH Ikeshima, T Zhao, YQ Wu, CF AF Bi, XL Yang, JY Dong, YX Wang, JM Cui, YH Ikeshima, T Zhao, YQ Wu, CF TI Resveratrol inhibits nitric oxide and TNF-alpha production by lipopolysaccharide-activated microglia SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE resveratrol; microglia; NO; TNF-alpha; I kappa B alpha; p38 ID NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; C6 GLIOMA-CELLS; PROTEIN-KINASES; DOWN-REGULATION; CHEMOPREVENTIVE PROPERTIES; SYNTHASE EXPRESSION; NEURONAL APOPTOSIS; EPITHELIAL-CELLS; GENE-EXPRESSION AB Upon activation, brain macrophages, the microglia, release proinflammatory mediators that play important roles in eliciting neuroinflammatory responses associated with neurodegenerative diseases. As resveratrol, an antioxidant component of grape, has been reported to exert anti-inflammatory activities on macrophages, we investigated its effects on the production of TNF-alpha (TNF-alpha) and nitric oxide (NO) by lipopolysaccharide (LPS)-activated microglia. Exposure of cultured rat cortical microglia and a mouse microglial cell line N9 to LPS increased their release of TNF-alpha and NO, which was significantly inhibited by resveratrol. Further studies revealed that resveratrol suppressed LPS-induced degradation of IkappaBalpha, expression of NOS and phosphorylation of p38 mitogen-activated protein kinases (MAPKs) in N9 microglial cells. These results demonstrate a potent suppressive effect of resveratrol on proinflammatory responses of microglia, suggesting a therapeutic potential for this compound in neurodegenerative diseases accompanied by microglial activation. (C) 2004 Elsevier B.V. All rights reserved. C1 Shenyang Pharmaceut Univ, Dept Pharmacol, Shenyang 110016, Peoples R China. SAIC Frederick, Mol Immunoregulat Lab, Canc Res Ctr, Natl Canc Inst, Frederick, MD USA. Lanzhou Mil Med Univ, Biochem Sect, Lanzhou, Peoples R China. Shenyang Pharmaceut Univ, Sino Japan Inst Med, Shenyang 110016, Peoples R China. RP Wu, CF (reprint author), Shenyang Pharmaceut Univ, Dept Pharmacol, Shenyang 110016, Peoples R China. EM wuchunf@21cn.com NR 56 TC 147 Z9 155 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD JAN PY 2005 VL 5 IS 1 BP 185 EP 193 DI 10.1016/j.intimp.2004.08.008 PG 9 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 891XX UT WOS:000226615400028 PM 15589480 ER PT J AU Engdahl, B Tambs, K Borchgrevink, HM Hoffman, HJ AF Engdahl, B Tambs, K Borchgrevink, HM Hoffman, HJ TI Otoacoustic emissions in the general adult population of Nord-Trondelag, Norway: III. Relationships with pure-tone hearing thresholds SO INTERNATIONAL JOURNAL OF AUDIOLOGY LA English DT Article DE otoacoustic emissions; hearing loss; age; sex ID DISTORTION-PRODUCT EMISSIONS; IMPAIRED SUBJECTS; TEST-PERFORMANCE; EARS; AGE; DISTRIBUTIONS; 2F(1)-F(2); AUDIOGRAM; HUMANS; DPOAE AB This study aims to describe the association between otoacoustic emissions (OAEs) and pure-tone hearing thresholds (PTTs) in an unscreened adult population (N =6415), to determine the efficiency by which TEOAEs and DPOAEs can identify ears with elevated PTTs, and to investigate whether a combination of DPOAE and TEOAE responses improves this performance. Associations were examined by linear regression analysis and ANOVA. Test performance was assessed by receiver operator characteristic (ROC) curves. The relation between OAEs and PTTs appeared curvilinear with a moderate degree of non-linearity. Combining DPOAEs and TEOAEs improved performance. Test performance depended on the cut-off thresholds defining elevated PTTs with optimal values between 25 and 45 dB HL, depending on frequency and type of OAE measure. The unique constitution of the present large sample, which reflects the general adult population, makes these results applicable to population-based studies and screening programs. C1 Norwegian Inst Publ Hlth, Div Epidemiol, N-0407 Oslo, Norway. Natl Hosp, Oslo, Norway. NIDCD, NIH, Bethesda, MD USA. RP Engdahl, B (reprint author), Norwegian Inst Publ Hlth, Div Epidemiol, POB 4404 Torshov, N-0407 Oslo, Norway. EM bo.engdahl@fhi.no FU NIDCD NIH HHS [N01 DC-6-2104] NR 40 TC 2 Z9 3 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1499-2027 J9 INT J AUDIOL JI Int. J. Audiol. PD JAN PY 2005 VL 44 IS 1 BP 15 EP 23 DI 10.1080/14992020400022504 PG 9 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 909AA UT WOS:000227830100003 PM 15796098 ER PT J AU Chesney, MA Darbes, LA Hoerster, K Taylor, JM Chambers, DB Anderson, DE AF Chesney, MA Darbes, LA Hoerster, K Taylor, JM Chambers, DB Anderson, DE TI Positive emotions: Exploring the other hemisphere in behavioral medicine SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article; Proceedings Paper CT International Congress of Behavioral Medicine CY AUG, 2002 CL Helsinki, FINLAND DE positive affect; emotion; health; behavioral medicine ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; PHYSICAL HEALTH; NEGATIVE AFFECT; SOCIAL SUPPORT; CARDIOVASCULAR-DISEASE; COMMUNITY SAMPLE; COMMON COLD; RISK-FACTOR; FOLLOW-UP AB The search for the psychological antecedents medical disorders has focused on the role of stress and negative emotional states. Previous research in this area has investigated relations between negative emotions and physiological adaptations (e.g., blood pressure elevations), adverse health behaviors (e.g., smoking), and social conditions (e.g., social isolation). In this discussion, we argue that more attention is needed to understand the effects of positive emotional states on health enhancement and disease prevention. In each of the areas cited previously, evidence is beginning to emerge that indicates that positive emotions can he associated with health promoting conditions. Interventions using cognitive behavioral strategies or meditation can increase positive emotional states that are maintained over time and that may benefit health and well-being. Implications for behavioral medicine tire discussed. C1 Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. NIA, NIH, Bethesda, MD USA. RP Chesney, MA (reprint author), Natl Ctr Complementary & Alternat Med, NIH, 31 Ctr Dr,Room 2B11,MSC 2182, Bethesda, MD 20892 USA. EM chesneym@mail.nih.gov FU NIMH NIH HHS [R01 MH57233, P30-MH62246] NR 97 TC 30 Z9 33 U1 6 U2 16 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 2005 VL 12 IS 2 BP 50 EP 58 DI 10.1207/s15327558ijbm1202_2 PG 9 WC Psychology, Clinical SC Psychology GA 933BE UT WOS:000229598100002 PM 15901213 ER PT J AU Lim, JH Luo, T Sargent, TD Fallon, JR AF Lim, JH Luo, T Sargent, TD Fallon, JR TI Developmental expression of Xenopus Fragile X mental retardation-1 gene SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE Fmr1; Fragile x syndrome; neural crest; Xenopus ID XENOPUS; FXR1 AB Dysregulation of Fragile X mental retardation-1 (Fmr1) gene expression results in an inherited form of mental retardation known as the Fragile X syndrome (FXS). Fmr1 is a highly conserved gene with a broad yet distinctive expression pattern during vertebrate development. Here, we examined the expression pattern of Fmr1 during Xenopus embryonic development. Zygotic expression of Fmr1 began just prior to gastrulation and gradually increased during subsequent embryonic stages. By in situ hybridization, Fmr1 transcripts were detected by early tailbud stage and showed robust expression in the central nervous system (CNS), eye and pharyngeal arches. By late tailbud stage, Fmr1 expression became stronger in the CNS and craniofacial regions including the ear vesicle and eye. In addition, the notochord expressed high levels of Fmr1 transcripts in the late tailbud stage embryos. In the tadpole brain, the olfactory bulb and cerebellum exhibited strong Fmr1 expression. The developmental expression pattern of Fmr1 is consistent with the wide range of abnormalities observed in FXS. Further, our findings indicate that Xenopus will serve as an excellent model to study the developmental basis of this disease. C1 Brown Univ, Dept Neurosci, Providence, RI 02912 USA. NICHD, Mol Genet Lab, NIH, Bethesda, MD USA. RP Fallon, JR (reprint author), Brown Univ, Dept Neurosci, Box 1953,190 Thayer St, Providence, RI 02912 USA. EM Justin_Fallon@brown.edu FU NCRR NIH HHS [P20 RR015578-060002, P20 RR015578, RR15578]; NIMH NIH HHS [MH065094-02]; NINDS NIH HHS [P01 NS039321, P01 NS039321-050002, NS39321] NR 9 TC 9 Z9 10 U1 2 U2 3 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 2005 VL 49 IS 8 BP 981 EP 984 DI 10.1387/ijdb.052070jl PG 4 WC Developmental Biology SC Developmental Biology GA 994PU UT WOS:000234044500010 PM 16281176 ER PT J AU Dolan-Sewell, R Insel, TR AF Dolan-Sewell, R Insel, TR TI Special Issue on Anorexia Nervosa SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Editorial Material C1 NIMH, Dept Hlth & Human Serv, US Govt, NIH, Bethesda, MD 20892 USA. RP Dolan-Sewell, R (reprint author), NIMH, Dept Hlth & Human Serv, US Govt, NIH, Room 6183,MSC 9625,6001 Execut Blvd, Bethesda, MD 20892 USA. EM rdolan@mail.nih.gov NR 3 TC 2 Z9 2 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PY 2005 VL 37 SU S BP S1 EP S1 DI 10.1002/eat.20106 PG 1 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 924LS UT WOS:000228980900001 ER PT J AU Stoltzfus, P Heselmeyer-Haddad, K Castro, J White, N Silfversward, C Sjovall, K Einhorn, N Tryggvason, K Auer, G Ried, T Nordstrom, B AF Stoltzfus, P. Heselmeyer-Haddad, K. Castro, J. White, N. Silfversward, C. Sjovall, K. Einhorn, N. Tryggvason, K. Auer, G. Ried, T. Nordstrom, B. TI Gain of chromosome 3q is an early and consistent genetic aberration in carcinomas of the vulva SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE chromosome 3q; laminin-5 gamma 2 chain; VIN; vulvar carcinoma ID SQUAMOUS-CELL CARCINOMA; COMPARATIVE GENOMIC HYBRIDIZATION; LAMININ-5 GAMMA-2 CHAIN; INTRAEPITHELIAL NEOPLASIA; HUMAN-PAPILLOMAVIRUS; RECURRENT PATTERN; CANCER; TISSUES; MARKER; CERVIX AB The aim was to determine whether specific gains of chromosome 3q and laminin-5 gamma 2-chain expression can improve early detection of invasive capacity in precancerous and squamous cell carcinoma of the vulva (VSCC). Six VSCC and three precancerous lesions were studied. Multicolor fluorescence in situ hybridization (FISH) probe sets were applied to nuclei suspensions prepared from archival material using the Hedley method. The probe panel consists of the centromers of chromosome 7, chromosome 3, and the TERC gene residing on the long arm of chromosome 3. Laminin-5 gamma 2-chain immunohistochemical analysis was performed on corresponding specimens and was expressed only in the VSCC. The genome-specific FISH analysis revealed 3q amplification in 43% of the nuclei analyzed for the VSCC and 22% of the nuclei for the precancerous lesions. Low-level 3q amplifications were found in precancerous lesions with an average fold increase of 1.15 for 3q. The invasive lesions showed higher average fold increases for 3q, averaging 1.32. Laminin-5 gamma 2-chain protein was expressed only in VSCC, whereas 3q gains were observed both in precancerous lesions and in VSCC, indicating that gain of chromosome 3q is an early and consistent event during carcinogenesis of VSCC. C1 Dept Pathol & Oncol, Stockholm, Sweden. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. Karolinska Hosp, Dept Obstet & Gynecol, S-10401 Stockholm, Sweden. Karolinska Inst, Stockholm, Sweden. RP Nordstrom, B (reprint author), Karolinska Hosp, Radiumhemmet, S-17176 Stockholm, Sweden. EM brita.nordstrom@karolinska.se NR 35 TC 5 Z9 5 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD JAN-FEB PY 2005 VL 15 IS 1 BP 120 EP 126 DI 10.1111/j.1048-891X.2005.15012.x PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 890MG UT WOS:000226514700018 PM 15670306 ER PT J AU Boss, LP Evans, D Ramos-Bonoan, C Liao, W Taggart, V Redd, SC AF Boss, LP Evans, D Ramos-Bonoan, C Liao, W Taggart, V Redd, SC TI Ensuring a scientific basis for community interventions for asthma SO INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH LA English DT Article DE asthma; intervention; physicians; research; public health clinics ID GUIDELINES; CHILDREN; CARE AB Community based interventions are an important part of public health management of many diseases, including asthma. However, there are few scientifically proven and readily available community interventions for asthma. In an effort to increase the number of available interventions, we have identified ongoing asthma intervention research, identified potentially effective asthma interventions based on completed research, and prepared several of the effective interventions for widespread implementation through a process called "translation." We provide an example of one of these effective interventions now available for widespread implementation, "Creating a medical home for asthma." This intervention grew out of need for an intervention in New York City Department of Health (NYCDOH) clinics. The intervention includes training all clinic staff in a comprehensive, preventive approach to asthma care. All of the materials needed to implement the intervention are available to all through the NYCDOH web site (www.nyc.gov/html/doh/html/cmha/index.html). This example points to the importance of making the tools needed to implement effective interventions available across the country and the role of public/private partnerships to assure the availability of science-based interventions for asthma control. Published by Elsevier GmbH. C1 Ctr Dis Control & Prevent, Atlanta, GA USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. New York City Dept Hlth, New York, NY USA. RTI Int, Res Triangle Pk, NC USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Boss, LP (reprint author), 1667 Alderbrook Rd, Atlanta, GA 30333 USA. EM lpboss@earthlink.net NR 9 TC 2 Z9 2 U1 0 U2 2 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 1438-4639 J9 INT J HYG ENVIR HEAL JI Int. J. Hyg. Environ. Health. PY 2005 VL 208 IS 1-2 BP 21 EP 25 DI 10.1016/j.ijheh.2005.01.004 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 927PV UT WOS:000229207400004 PM 15881975 ER PT J AU Wada, A Wang, AP Isomoto, H Satomi, Y Takao, T Takahashi, A Awata, S Nomura, T Fujii, Y Kohno, S Okamoto, K Moss, J Millan, JL Hirayama, T AF Wada, A Wang, AP Isomoto, H Satomi, Y Takao, T Takahashi, A Awata, S Nomura, T Fujii, Y Kohno, S Okamoto, K Moss, J Millan, JL Hirayama, T TI Placental and intestinal alkaline phosphatases are receptors for Aeromonas sobria hemolysin SO INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article DE Aeromonas sobria; hemolysin; diarrhea; receptor; PLAP; IAP ID FORMING TOXIN AEROLYSIN; GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHORED PROTEIN; LIPID RAFTS; CYTOTONIC ENTEROTOXIN; CHOLERA-TOXIN; ALPHA-TOXIN; HYDROPHILA; PURIFICATION; BINDING; GENES AB The Aeromonas sobria hemolysin causes diarrhea following infection by this enteropathogenic bacterium. We previously identified the putative receptor for A. sobria hemolysin as a p66 protein on Intestine 407 cells (Microb. Pathog. 27 (1999) 215-221). Here, we have partially purified and obtained a peptide mass fingerprint of p66 which revealed its identity with placental alkaline phosphatase (PLAP). Recombinant PLAP expressed in 293T cells was also found to bind to hemolysin and the binding was found not to be dependent on the N-linked glycosylation of PLAP. By immunohistochemical analysis, PLAP expression was detected in human intestinal mucosa, the target tissue in disease. In addition to PLAP, hemolysin also binds to intestinal alkaline phosphatase (IAP), an enzyme that is also abundantly expressed in intestine. Thus, both PLAP and IAP are very likely involved in the pathogenesis of diarrhea caused by this bacterial toxin. (C) 2004 Elsevier GmbH. All rights reserved. C1 Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 8528523, Japan. Nagasaki Univ, Sch Med, Dept Internal Med 2, Nagasaki 8528523, Japan. Osaka Univ, Inst Prot Res, Lab Protem Profiling & Funct Prote, Osaka, Japan. Univ Tokushima, Sch Med, Dept Nutr, Tokushima 770, Japan. Tokushima Bunri Univ, Fac Pharmaceut Sci, Dept Biochem, Tokushima 770, Japan. Tokushima Bunri Univ, Fac Pharmaceut Sci, Inst Pharmacognosy, Tokushima 770, Japan. Okayama Univ, Fac Pharmaceut Sci, Okayama 700, Japan. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. Burnham Inst, La Jolla, CA 92037 USA. RP Hirayama, T (reprint author), Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 8528523, Japan. EM hirayama@net.nagasaki-u.ac.jp RI Millan, Jose Luis/B-6580-2008; OKAMOTO, Keinosuke/B-2257-2011; OI Satomi, Yoshinori/0000-0002-8991-1040 FU NCI NIH HHS [CA 42595] NR 34 TC 4 Z9 5 U1 0 U2 1 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 1438-4221 J9 INT J MED MICROBIOL JI Int. J. Med. Microbiol. PD JAN PY 2005 VL 294 IS 7 BP 427 EP 435 DI 10.1016/j.ijmm.2004.09.012 PG 9 WC Microbiology; Virology SC Microbiology; Virology GA 895DB UT WOS:000226840000002 PM 15715171 ER PT J AU Wittchen, HU Merikangas, KR AF Wittchen, HU Merikangas, KR TI Untitled SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH LA English DT Editorial Material C1 Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, Dresden, Germany. NIMH, Sect Dev Genet Epidemiol, Bethesda, MD USA. RP Wittchen, HU (reprint author), Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, Dresden, Germany. EM wittchen@psychologie.tu-dresden.de RI Wittchen, Hans-Ulrich/A-8507-2014 NR 0 TC 1 Z9 1 U1 0 U2 0 PU WHURR PUBLISHERS LTD PI LONDON PA 19B COMPTON TERRACE, LONDON N1 2UN, ENGLAND SN 1049-8931 J9 INT J METH PSYCH RES JI Int. J. Methods Psychiatr. Res. PY 2005 VL 14 IS 1 BP 1 EP 2 DI 10.1002/mpr.12 PG 2 WC Psychiatry SC Psychiatry GA 919AU UT WOS:000228591500001 ER PT J AU Norris, JM Langefeld, CD Scherzinger, AL Rich, SS Bookman, E Beck, SR Saad, MF Haffner, SM Bergman, RN Bowden, DW Wagenknecht, LE AF Norris, JM Langefeld, CD Scherzinger, AL Rich, SS Bookman, E Beck, SR Saad, MF Haffner, SM Bergman, RN Bowden, DW Wagenknecht, LE TI Quantitative trait loci for abdominal fat and BMI in Hispanic-Americans and African-Americans: the IRAS Family Study SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE genome scan; linkage analysis; subcutaneous fat; adiposity; Hispanic-American; visceral fat; genetics; African-American ID BODY-MASS INDEX; GENOME-WIDE SCAN; VISCERAL FAT; LINKAGE ANALYSIS; HERITAGE FAMILY; QUEBEC FAMILY; METABOLIC SYNDROME; OBESITY; GENE; ADIPOSITY AB Objective: To conduct linkage analysis for body mass index (BMI, kg/m(2)), waist-to-hip ratio (WHR), visceral adipose tissue mass (VAT, cm(2)) and subcutaneous adipose tissue mass (SAT, cm(2)) using a whole genome scan. Design: Cross-sectional family study. Study Subjects: African-American families from Los Angeles (AA, n=21 extended pedigrees) and Hispanic-American families (HA) from San Antonio, TX (HA-SA, n=33 extended pedigrees) and San Luis Valley, CO (HA-SLV, n=12 extended pedigrees), totaling 1049 individuals in the Insulin Resistance and Atherosclerosis (IRAS) Family Study. Measurements: VAT and SAT were measured using a computed tomography scan obtained at the fourth and fifth lumbar vertebrae. All phenotypes were adjusted for age, gender, and study center. VAT, SAT, and WHR were analyzed both unadjusted and adjusted for BMI. Results: Significant linkage to BMI was found at D3S2387 (LOD=3.67) in African-Americans, and at D17S1290 in Hispanic-Americans (LOD=2.76). BMI-adjusted WHR was linked to 12q13-21 (D12S297 (LOD=2.67) and D12S1052 (LOD=2.60)) in Hispanic-Americans. The peak LOD score for BMI-adjusted VAT was found at D11S2006 (2.36) in Hispanic families from San Antonio. BMI-adjusted SAT was linked to D5S820 in Hispanic families (LOD=2.64). Evidence supporting linkage of WHR at D11S2006, VAT at D17S1290, and SAT at D1S1609, D3S2387, and D6S1056 was dependent on BMI, such that the LOD scores became nonsignificant after adjustment of these phenotypes for BMI. Conclusions: Our findings both replicate previous linkage regions and suggest novel regions in the genome that may harbor quantitative trait locis contributing to variation in measures of adiposity. C1 Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. Univ Colorado, Hlth Sci Ctr, Dept Radiol, Denver, CO 80262 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Biochem, Winston Salem, NC 27103 USA. Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Gen, Winston Salem, NC 27103 USA. RP Norris, JM (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, 4200 E 9th Ave,Box B119, Denver, CO 80262 USA. EM jill.norris@uchsc.edu RI Beck-Roth, Stephanie/B-8167-2009 FU NHLBI NIH HHS [HL060894, HL0601019, HL06091, HL060919, HL060944, HL061210] NR 38 TC 28 Z9 28 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD JAN PY 2005 VL 29 IS 1 BP 67 EP 77 DI 10.1038/sj.ijo.0802793 PG 11 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 879IS UT WOS:000225710800010 PM 15534617 ER PT J AU Alvarez-Salas, LM Benitez-Hess, ML Dipaolo, JA AF Alvarez-Salas, LM Benitez-Hess, ML Dipaolo, JA TI YY-1 and c-Jun transcription factors participate in the repression of the human involucrin promoter SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE transcription; involucrin; AP-1 transcription factor; YY1 transcription factor; epithelial differentiation ID SERUM RESPONSE FACTOR; TERMINAL DIFFERENTIATION; HUMAN KERATINOCYTES; IN-VITRO; MULTIPLE MECHANISMS; ACTIVATOR PROTEIN-1; BINDING PROTEIN; GENE CONTAINS; AP-1 ACTIVITY; EXPRESSION AB The human involucrin gene, which encodes a precursor of the keratinocyte cornified layer, is strongly expressed in response to differentiation stimuli. Earlier studies suggested that YY1 and components of the AP-1 family might participate in the silencing of involucrin in proliferating keratinocytes. This study shows that overexpression of either YY1 or c-Jun represses transcription of the human involucrin gene in multiplying keratinocytes. Transient overexpression and site-directed mutagenesis experiments of the involucrin 5'-non-coding region (5'-NCR) confirmed that YY1 and c-Jun repress involucrin transcription. This repression involves the distal zinc fingers of YY1 protein and the DNA binding and leucine zipper domains of c-Jun. The results with protein pull-down experiments are consistent with the hypothesis that interaction of YY1 with c-Jun is an important mechanism for involucrin repression. Cotransfection of YY1 modified the stimulatory function of mutant c-Jun proteins independently of their DNA binding capacity suggesting that interactions may be more complex in vivo. Additionally, c-Jun protein levels are affected by differentiation stimuli indicating the importance of c-Jun in the YY1 repression pathway. Thus YY1 and c-Jun have an important role in epidermal differentiation by negatively regulating the human involucrin gene. C1 Ctr Invest & Estud Avanzados, Dept Genet & Biol Mol, Lab Terapia Gen, Mexico City 07360, DF, Mexico. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Alvarez-Salas, LM (reprint author), Ctr Invest & Estud Avanzados, Dept Genet & Biol Mol, Lab Terapia Gen, Mexico City 07360, DF, Mexico. EM lalvarez@mail.cinvestav.mx NR 55 TC 11 Z9 12 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 2005 VL 26 IS 1 BP 259 EP 266 PG 8 WC Oncology SC Oncology GA 884RV UT WOS:000226104600030 PM 15586248 ER PT J AU Datta, K Neumann, RD Winters, TA AF Datta, K Neumann, RD Winters, TA TI Characterization of a complex I-125-induced DNA double-strand break: Implications for repair SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID CELL-FREE-EXTRACTS; IONIZING-RADIATION; 3'-PHOSPHOGLYCOLATE TERMINI; BIOLOGICAL CONSEQUENCES; ENERGY DEPOSITION; MAMMALIAN-CELLS; AUGER ELECTRONS; PROTEIN-KINASE; LIGASE-IV; IN-VITRO AB Purpose: To examine the role of radiation- induced DNA double- strand break ( DSB) structural organization in DSB repair, and characterize the structural features of I-125- induced DSBs that may impact the repair process. Methods: Plasmid DNA was linearized by sequence- specific targeting using an I-125- labeled triplex- forming oligonucleotide ( TFO). Following isolation from agarose gels, base damage structures associated with the DSB ends in plasmids linearized by the I-125- TFO were characterized by probing with the E. coli DNA damage- specific endonuclease and DNA- glycosylases, endonuclease IV ( endo IV), endonuclease III ( endo III), and formamidopyrimidine- glycosylase ( Fpg). Results: Plasmid DNA containing DSBs produced by the high- LET- like effects of I-125- TFO has been shown to support at least 2- fold lower end joining than γ- ray linearized plasmid, and this may be a consequence of the highly complex structure expected near an I-125- induced DSB end. Therefore, to determine if a high density of base damage exists proximal to the DSBs produced by I-125- TFOs, short fragments of DNA recovered from the DSB end of I-125- TFO- linearized plasmid were enzymatically probed. Base damage and AP site clustering was demonstrated within 3 bases downstream and 7 bases upstream of the targeted base. Furthermore, the pattern and extent of base damage varied depending upon the presence or absence of 2 M DMSO during irradiation. Conclusions: I-125- TFO- induced DSBs exhibit a high degree of base damage clustering proximal to the DSB end. At least 60% of the nucleotides within 10 bp of the I-125 decay site are sensitive to cleavage by endo IV, endo III, or Fpg following damage accumulation in the presence of DMSO, whereas &GE; 80% are sensitive in the absence of DMSO. The high degree of base damage clustering associated with the I-125- TFO- induced DSB end may be a major factor leading to its negligible in vitro repair by the non- homologous end- joining pathway ( NHEJ). C1 NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Winters, TA (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. EM twinters@mail.cc.nih.gov NR 41 TC 12 Z9 13 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD JAN PY 2005 VL 81 IS 1 BP 13 EP 21 DI 10.1080/09553000400017713 PG 9 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 925UT UT WOS:000229079500002 PM 15962759 ER PT J AU Barker, CA Burgan, WE Carter, DJ Camphausen, K Tofilon, PJ AF Barker, CA Burgan, WE Carter, DJ Camphausen, K Tofilon, PJ TI 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine): A ribonucleotide reductase inhibitor with potent radiosensitizing properties SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 16-20, 2005 CL Denver, CO SP Amer Soc Therapeut Radiol & Oncol C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Mol Radiat Therapeut Branch, Bethesda, MD 20892 USA. RI Barker, Christopher/I-9477-2012 NR 0 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2005 VL 63 IS 2 SU 1 MA 1042 BP S170 EP S170 DI 10.1016/j.ijrobp.2005.07.292 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 967HW UT WOS:000232083300288 ER PT J AU Barra, S Vitale, V Dallorso, S Milanaccio, C Foppiano, F Guenzi, M Rossi, A Pavanello, M Nozza, P Cama, A Garre, M AF Barra, S Vitale, V Dallorso, S Milanaccio, C Foppiano, F Guenzi, M Rossi, A Pavanello, M Nozza, P Cama, A Garre, M TI Craniospinal reduced dose radiotherapy after myeoablative chemotherapy with peripheral blood stem cells rescue, in high risk medulloblastoma: Results of a mono-institutional study in Italy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 16-20, 2005 CL Denver, CO SP Amer Soc Therapeut Radiol & Oncol C1 Natl Canc Inst, Genoa, Italy. Gaslini Childrens Hosp, Genoa, Italy. RI Rossi, Andrea/A-4146-2011 OI Rossi, Andrea/0000-0001-8575-700X NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2005 VL 63 IS 2 SU 1 MA 044 BP S25 EP S25 DI 10.1016/j.ijrobp.2005.07.050 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 967HW UT WOS:000232083300047 ER PT J AU Li, G Xie, H Ning, H Citrin, D Capala, J Arora, BC Coleman, CN Camphausen, K Miller, BW AF Li, G Xie, H Ning, H Citrin, D Capala, J Arora, BC Coleman, CN Camphausen, K Miller, BW TI A clinical application of volume-view-guided image registration of four concurrent Imaging modalities: CT/MR1/MR2/PET SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 16-20, 2005 CL Denver, CO SP Amer Soc Therapeut Radiol & Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2005 VL 63 IS 2 SU 1 MA 231 BP S138 EP S139 DI 10.1016/j.ijrobp.2005.07.237 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 967HW UT WOS:000232083300234 ER PT J AU Mansueti, JR Singh, AK Guion, P Ning, H Savani, B Barrett, J Karimpour, SE AF Mansueti, JR Singh, AK Guion, P Ning, H Savani, B Barrett, J Karimpour, SE TI Pre-stem cell transplant pulmonary function tests (PFTs) predict risk of mortality in the absence of pulmonary lung shielding with fractionated total body irradiation (TBI) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 16-20, 2005 CL Denver, CO SP Amer Soc Therapeut Radiol & Oncol C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2005 VL 63 IS 2 SU 1 MA 2332 BP S427 EP S427 DI 10.1016/j.ijrobp.2005.07.727 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 967HW UT WOS:000232083301241 ER PT J AU Miller, RW Ning, H Justus, B Huston, A Falkenstein, P Li, G Xie, H Coleman, CN AF Miller, RW Ning, H Justus, B Huston, A Falkenstein, P Li, G Xie, H Coleman, CN TI Clinical implementation of a real-time fiberoptic dosimetry system SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 16-20, 2005 CL Denver, CO SP Amer Soc Therapeut Radiol & Oncol C1 Natl Canc Inst, Radiat Oncol Branch, Bethesda, MD USA. USN, Res Lab, Div Opt Sci, Washington, DC 20375 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2005 VL 63 IS 2 SU 1 MA 2446 BP S494 EP S494 DI 10.1016/j.ijrobp.2005.07.841 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 967HW UT WOS:000232083301355 ER PT J AU Panandiker, AP Ning, H Miller, R Arora, B Karimpour, S AF Panandiker, AP Ning, H Miller, R Arora, B Karimpour, S TI A new technique and verification for pediatric cranial-spinal irradiation in supine position SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 16-20, 2005 CL Denver, CO SP Amer Soc Therapeut Radiol & Oncol C1 NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2005 VL 63 IS 2 SU 1 MA 2364 BP S444 EP S445 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 967HW UT WOS:000232083301273 ER PT J AU Beaty, MW Quezado, M Sobel, ME Duray, P Merino, MJ AF Beaty, MW Quezado, M Sobel, ME Duray, P Merino, MJ TI Loss of heterozygosity on chromosome 1 and 9 and hormone receptor analysis of metastatic malignant melanoma presenting in breast SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE melanoma; metastasis; breast; loss of heterozygosity; p15 gene; chromosome 9q22.3; hormone receptors ID CELL-CARCINOMA-SYNDROME; HOMOZYGOUS DELETIONS; CUTANEOUS MELANOMA; ALLELIC DELETIONS; GENE; ESTROGEN; LOCALIZATION; PROGRESSION; DIAGNOSIS; CANCERS AB Malignant melanoma (MM), the most common metastatic solid tumor to involve the breast, may present as a diagnostic problem, frequently requiring the use of ancillary studies for accurate diagnosis. The implication of hormonal interplay is strong since metastatic MM to the breast is seen nearly always in women. However, the role of hormonal status as a predisposing factor in the development of this entity is largely unresolved. A number of chromosomal loci, including 1p36 and 9p21-22, appear to harbor critical genes important to melanoma tumorigenesis, and additionally chromosome 9q22.3-31. We wanted to know if metastatic MM in breast showed chromosome 1p and 9p genetic alterations (loss of heterozygosity) similar to those that occur in primary cutaneous MM, and whether additional 9q LOH changes are present. Hormonal receptor status of the metastatic MM was also determined. We identified 20 patients with known MM metastatic to the breast, which we analyzed with the following genetic markers: D9S12 (9q22.3), D9S171 (9p21), IFNA (9p22), and D1S450 (1p). Visually directed microdissection was performed on archival histologic slides containing both tumor and adjacent normal breast epithelium, followed by single-step DNA extraction and polymerase chain reaction (PCR) amplification for evaluation of loss of heterozygosity (LOH) for the above-listed markers. Immunohistochemical (IHC) stains for estrogen receptor (ER) and progesterone receptor (PR) was performed on 10 of the cases. Twelve of the 20 cases contained DNA suitable for PCR amplification following direct visualization microdissection. Four of 8 (50%) informative cases showed LOH at 9p21 with D9S171. Ten cases were heterozygous for IFNA, with 2 cases (20%) showing LOH at this locus. These particular cases also showed LOH at 9p21. One of 9 (11%) informative cases showed LOH for D1S450 (1p36). Five cases were heterozygous for D9S12, and 2 (40%) showed LOH in the tumor at 9q22.3. IHC stains for ER and PR were negative in the 10 tumors studied. Metastatic MM. presenting as a breast mass is an interesting entity often requiring IHC studies for diagnosis, particularly when the histologic features simulate breast carcinoma or when no primary tumor is known. These tumors are ER and PR negative. Metastatic MM involving the breast shows similar genetic allelic losses on chromosome 9p21-22 (50%) and 1p36 (11%), as previously described in primary cutaneous MM. Additional LOH was observed at the 9q22.3-31 locus (40%). We suggest this locus to be investigated for harboring potential genes important in the tumorigenesis of cutaneous MM. C1 NIH, Pathol Lab, NCI, Bethesda, MD 20892 USA. RP Merino, MJ (reprint author), NIH, Pathol Lab, NCI, Bldg 10,Room 2N212,10 Ctr Dr, Bethesda, MD 20892 USA. NR 41 TC 5 Z9 6 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD JAN PY 2005 VL 13 IS 1 BP 9 EP 18 DI 10.1177/106689690501300102 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 898JV UT WOS:000227074000002 PM 15735850 ER PT J AU Waalkes, MP Liu, J Kasprzak, KS Diwan, BA AF Waalkes, MP Liu, J Kasprzak, KS Diwan, BA TI Metallothionein-I/II double knockout mice are no more sensitive to the carcinogenic effects of nickel subsulfide than wild-type mice SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE carcinogenesis; metallothionein deficient; mice; nickel; sarcoma ID OXIDATIVE STRESS; TRANSGENIC MICE; GENE-EXPRESSION; II GENES; CADMIUM; INDUCTION; TOXICITY; CULTURES; METALS; DAMAGE AB Metallothionein (MT) is a high-affinity metal-binding protein thought to mitigate the toxicity of various metals. MT may limit the toxicity of a metal by direct binding or through action as an antioxidant for metals that generate reactive oxygen species. Nickel compounds have carcinogenic potential in humans and animals, possibly by production of oxidative stress. The impact of MT deficiency on the carcinogenic effects of nickel is unknown. Thus, groups (n = 25) of male MT-I/II double knockout (MT-null) or MT wild-type (WT) mice were exposed to a single treatment of nickel (0.5 or 1.0 mg Ni3S2/site, intramuscularly, [i.m.], into both hind legs), or left untreated (control) and observed over the next 104 weeks. There were no differences in the incidence of spontaneous tumors in MT-null and WT mice. Nickel induced injection site fibrosarcomas in a dose-related fashion to a similar extent in both WT and MT-null mice. Nickel-treatment had no effect on total lung tumor incidence, although some phenotypic-specific differences occurred in the proportion of benign and malignant pulmonary tumors. Overall, MT-null mice appear no more sensitive to the carcinogenic effects of nickel than WT mice. Thus, poor MT production does not appear to be a predisposing factor for nickel carcinogenesis. C1 NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. NCI, Met Sect, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21701 USA. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, 111 Alexander Dr,POB 12233,MD F0-09, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 27 TC 10 Z9 11 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PY 2005 VL 24 IS 4 BP 215 EP 220 DI 10.1080/10915810591000668 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 955YX UT WOS:000231267200003 PM 16126615 ER PT J AU Lebowitz, B AF Lebowitz, B TI CATIE AD: Impact on quality of life and economic utilization SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Meeting Abstract C1 NIMH, Geriatr Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PY 2005 VL 17 SU 2 BP 57 EP 57 PG 1 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 984RQ UT WOS:000233322400096 ER PT J AU Lahiri, D Chen, DM Farlow, M Sambamurti, K Greig, N AF Lahiri, D Chen, DM Farlow, M Sambamurti, K Greig, N TI Cholinesterase inhibitors, beta-amyloid and Alzheimer's disease SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Meeting Abstract C1 Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PY 2005 VL 17 SU 2 BP 157 EP 157 PG 1 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 984RQ UT WOS:000233322400302 ER PT J AU Vaishampayan, U Heilbrun, LK Parchment, RE Jain, V Zwiebel, J Boinpally, RR LoRusso, P Hussain, M AF Vaishampayan, U Heilbrun, LK Parchment, RE Jain, V Zwiebel, J Boinpally, RR LoRusso, P Hussain, M TI Phase II trial of fenretinide in advanced renal carcinoma SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE fenretinide; N-4-hydroxyphenyl retinamide; renal cancer; clinical trial ID SYNTHETIC RETINOID FENRETINIDE; CANCER CELL-LINES; BREAST-CANCER; N-(4-HYDROXYPHENYL) RETINAMIDE; 13-CIS-RETINOIC ACID; APOPTOSIS; INTERFERON; GROWTH; NEUROBLASTOMA; INDUCTION AB Purpose: Fenretinide, a synthetic form of retinoid, induced apoptosis even in chemotherapy resistant cell lines. A phase II study was hence conducted to evaluate toxicity and efficacy of fenretinide in metastatic renal cancer. Methods: Eligibility included unresectable or metastatic renal cell carcinoma (RCC), adequate organ function and Zubrod performance status less than or equal to2. Prior immunotherapy and a maximum of one prior chemotherapy regimen were allowed. Fenretinide was administered at a dose of 900 mg/m(2) twice daily orally for 7 days in a 21-day cycle. Toxicity was assessed at the start of each cycle, and response every 2 cycles. Results: Nineteen eligible patients enrolled of which fifteen had visceral/bone metastases. Seventeen patients had prior nephrectomy and 11 had prior immunotherapy. 76 cycles of therapy were delivered. Therapy was very well tolerated with few severe toxicities consisting of thrombosis in 1 individual and grade 3 fatigue, nausea and diarrhea in 1 patient. 5 patients had grade 2 nyctalopia and 3 patients had transient grade 2 visual toxicity. No objective responses were noted. Stable disease was seen in seven of nineteen cases (37%, 90% C.I. 0.21-0.59). Median time to progression was 1.5 months and median duration of stable disease was 5.8 months (90% C.I. 3.0-8.4). Median survival was 10 months. Tumor fenretinide levels were obtained in three patients and were in the lower end of the therapeutic range. Conclusion: Fenretinide was well tolerated but demonstrated minimal activity that was consistent with results of intratumoral drug measurements. Strategies are needed that will increase systemic and tumor levels of fenretinide. C1 Wayne State Univ, Karmanos Canc Inst, Div Oncol, Detroit, MI 48201 USA. Wayne State Univ, Karmanos Canc Inst, Div Biostat Core, Detroit, MI 48201 USA. NCI, Bethesda, MD 20892 USA. Univ Michigan, Ctr Comprehens Canc, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Comprehens Canc, Dept Urol, Ann Arbor, MI 48109 USA. RP Vaishampayan, U (reprint author), Wayne State Univ, Karmanos Canc Inst, Div Oncol, 4th Floor Hudson Webber Canc Res Ctr,4100 John R, Detroit, MI 48201 USA. EM vaishamu@karmanos.org FU NCI NIH HHS [CA-22453, U01-CA-062487] NR 27 TC 30 Z9 30 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD JAN PY 2005 VL 23 IS 2 BP 179 EP 185 DI 10.1007/s10637-005-5864-7 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 903MJ UT WOS:000227429800011 PM 15744595 ER PT J AU Zillig, M Wurm, A Grehn, FJ Russell, P Tamm, ER AF Zillig, M Wurm, A Grehn, FJ Russell, P Tamm, ER TI Overexpression and properties of wild-type and Tyr437His mutated myocilin in the eyes of transgenic mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID HUMAN TRABECULAR MESHWORK; OPEN-ANGLE GLAUCOMA; GLUCOCORTICOID RESPONSE PROTEIN; INTRAOCULAR-PRESSURE; ENDOPLASMIC-RETICULUM; AQUEOUS-HUMOR; EXTRACELLULAR-MATRIX; IN-VITRO; OLFACTOMEDIN DOMAIN; CLINICAL-FEATURES AB PURPOSE. To obtain experimental in vivo information on the functional properties of myocilin for aqueous humor (AH) outflow and to study in vivo the processing of mutated Tyr437His myocilin. Myocilin is a secreted glycoprotein that is mutated in some forms of primary open-angle glaucoma (POAG), and patients with the Tyr437His mutation have severe phenotypes. METHODS. The chicken betaB1-crystallin promoter was used to overexpress wild-type human myocilin and mutated Tyr437His myocilin in the lenses of transgenic mice. Expression of transgenic mRNA was monitored by Northern blot analysis and in situ hybridization. The localization and secretion of transgenic myocilin was investigated by Western blot analysis and light and electron microscopy. Intraocular pressure (IOP) was measured by anterior chamber cannulation. RESULTS. Two independent lines were established with each of the constructs that showed a strong expression of transgenic mRNA in their lenses. Transgenic expression resulted in a 4.7 +/- 1.8-fold increase of secreted normal myocilin in mouse AH, compared with its concentration in human AH. Immunoreactivity for transgenic myocilin was observed along the surfaces of lens and corneal endothelium, and in the chamber angle. At 12 weeks of age, the ultrastructure of the trabecular meshwork in mice expressing normal myocilin was not different from that of control eyes, and IOP of transgenic animals did not significantly differ from that of control littermates. In contrast, mutated Tyr437His myocilin was not secreted from lens fibers, but accumulated in dilated cisterns of rough endoplasmic reticulum. Although no structural changes were observed in lenses of animals expressing normal myocilin, lenses with Tyr437His expression developed nuclear cataracts, completely lost transparency, and eventually ruptured. Structural changes in lenses of Tyr437His expressing mice were correlated with a significant increase in IOP. CONCLUSIONS. The results do not support the concept that increasing amounts of myocilin in the outflow tissues obstruct the system and directly cause an increase in outflow resistance. Mutated Tyr437His myocilin is not secreted in vivo and causes severe alterations of cellular structure and function. A comparable mechanism may cause POAG in patients with myocilin mutations. C1 Univ Erlangen Nurnberg, Lehrstuhl 2, Inst Anat, Dept Anat Mol Anat & Embryol, D-91054 Erlangen, Germany. Univ Wurzburg, Dept Ophthalmol, Wurzburg, Germany. NEI, NIH, Bethesda, MD 20892 USA. RP Tamm, ER (reprint author), Univ Erlangen Nurnberg, Lehrstuhl 2, Inst Anat, Dept Anat Mol Anat & Embryol, Univ Str 19, D-91054 Erlangen, Germany. EM ernst.tamm@anatomie2.med.uni-erlangen.de RI Grosche, Antje/N-1978-2014; OI Grosche, Antje/0000-0003-0338-7530; Tamm, Ernst/0000-0002-6679-8743 NR 82 TC 49 Z9 54 U1 0 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2005 VL 46 IS 1 BP 223 EP 234 DI 10.1167/iovs.04-0988 PG 12 WC Ophthalmology SC Ophthalmology GA 889UV UT WOS:000226469100033 PM 15623777 ER PT J AU Choudhary, S Xiao, TL Vergara, LA Srivastava, S Nees, D Piatigorsky, J Ansari, NH AF Choudhary, S Xiao, TL Vergara, LA Srivastava, S Nees, D Piatigorsky, J Ansari, NH TI Role of aldehyde dehydrogenase isozymes in the defense of rat lens and human lens epithelial cells against oxidative stress SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID LIPID-PEROXIDATION PRODUCT; MAJOR SOLUBLE-PROTEINS; ALDOSE REDUCTASE; HEPATOCELLULAR METABOLISM; HUMAN CORNEAL; ENZYMES; GLUTATHIONE; LIVER; ERYTHROCYTES; PURIFICATION AB PURPOSE. 4-Hydroxynonenal (HNE), a metastable lipid peroxidation product, is highly toxic to various cell types if not detoxified. Because of its constant exposure to light, the ocular lens continuously generates reactive oxygen species which, under conditions of oxidative stress, may lead to excessive lipid peroxidation and consequent formation of lipid-derived aldehydes (LDAs) such as HNE. The contribution of various isozymes of aldehyde dehydrogenase (ALDH) to the oxidation of LDAs has never been systematically investigated in the lens. The present study was undertaken to ascertain the role of ALDH1A1 and -3A1 in HNE metabolism and HNE-induced toxicity in cultured human lens epithelial cells (HLECs) and in rat and mouse lenses. METHODS. The metabolism of H-3-HNE was studied in ALDH3A1-knockout mouse lens and in HLECs transfected with ALDH1A1- or -3A1-specific antisense RNA and short interfering (Si) RNA. Appropriate controls were used, including wild-type mouse lens, scrambled oligonucleotides, and a transfection reagent. Transfected HLECs were exposed to oxidative stress (Fenton reaction) or HNE (30 muM) for 3 hours. Toxicity parameters, such as cell viability, apoptosis, and protein-HNE adducts and oxidation of exogenously added H-3-HNE were measured. Rat lenses were transfected with the SiRNA specific to ALDH1A1, and oxidation of H-3-HNE and the susceptibility of the transfected lenses to oxidation-induced opacification were measured. RESULTS. Rat lenses transfected with ALDH1A1- specific SiRNA, or cultured in the presence of the ALDH inhibitor cyanamide/disulfiram and subjected to oxidative stress displayed accelerated loss of transparency and a diminished capacity to oxidize HNE. Similarly, inhibition of ALDH1A1 in HLECs by ALDH1A1-specific antisense RNA or SiRNA was associated with decreased oxidation of H-3-HNE and increased susceptibility of the cells to oxidative damage, including apoptosis. Furthermore, H-3-HNE metabolism and HNE-induced toxicity were not affected in ALDH3A1-specific SiRNA- or antisense RNA-treated rat lenses, HLECs, or ALDH3A1-null mouse lenses. CONCLUSIONS. The results suggest that, under oxidative stress, HNE produced in the lens epithelium can cause toxicity and thus contribute to oxidation-induced cataractogenesis. Furthermore, the studies indicate that ALDH1A1 is a critical isozyme for maintaining clarity in human, rat, and mouse lenses. C1 Univ Texas, Med Branch, Dept Human Biol Chem & Genet, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Physiol & Biophys, Galveston, TX 77555 USA. Univ Louisville, Div Cardiol, Louisville, KY 40292 USA. NEI, Bethesda, MD 20892 USA. RP Ansari, NH (reprint author), Univ Texas, Med Branch, Dept Human Biol Chem & Genet, 6-644 Basic Sci Bldg,301 Univ Blvd, Galveston, TX 77555 USA. EM nansari@utmb.edu RI Srivastava, Sanjay/D-3921-2012 FU NEI NIH HHS [EY13014]; NHLBI NIH HHS [HL61618] NR 49 TC 48 Z9 54 U1 1 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2005 VL 46 IS 1 BP 259 EP 267 DI 10.1167/iovs.04-0120 PG 9 WC Ophthalmology SC Ophthalmology GA 889UV UT WOS:000226469100038 PM 15623782 ER PT J AU Ala-Laurila, P Estevez, M Crouch, RK Wiggert, B Cornwall, MC AF Ala-Laurila, P Estevez, M Crouch, RK Wiggert, B Cornwall, MC TI Production and clearance of all-trans retinol in bleached rods and cones depend on opsin type and photoreceptor morphology SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO 2005) CY MAY 01-05, 2005 CL Ft Lauderdale, FL SP Assoc Res Vision Ophthalmol C1 Boston Univ, Sch Med, Boston, MA 02215 USA. Med Univ S Carolina, Charlestown, MA USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PY 2005 VL 46 SU S MA 3968 PG 1 WC Ophthalmology SC Ophthalmology GA 911CZ UT WOS:000227980404259 ER PT J AU Boesze-Battaglia, K Damek-Poprawa, M Rachel, R Pankoski, L Copeland, N Jenkins, N AF Boesze-Battaglia, K Damek-Poprawa, M Rachel, R Pankoski, L Copeland, N Jenkins, N TI Photoreceptor peripherin/rds fusogenic function is inhibited by dsu, through direct binding to the C-terminal domain SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO 2005) CY MAY 01-05, 2005 CL Ft Lauderdale, FL SP Assoc Res Vision Ophthalmol C1 Univ Penn, Sch Dent Med, Philadelphia, PA 19104 USA. NCI, MCGP, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PY 2005 VL 46 SU S MA 3975 PG 1 WC Ophthalmology SC Ophthalmology GA 911CZ UT WOS:000227980404268 ER PT J AU Chew, EY Clemens, T Bressler, S Klein, M Ruby, A Seddon, J AF Chew, EY Clemens, T Bressler, S Klein, M Ruby, A Seddon, J CA AREDS Res Grp TI Serum nutrient levels as risk factors for neovascular AMD SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO 2005) CY MAY 01-05, 2005 CL Ft Lauderdale, FL SP Assoc Res Vision Ophthalmol C1 NEI, AREDS Res Grp, NIH, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. Wilmer Eye Inst, Baltimore, MD USA. Devers Eye Inst, Portland, OR USA. Associated Retina Consultants, Royal Oak, MI USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PY 2005 VL 46 SU S MA 3303 PG 1 WC Ophthalmology SC Ophthalmology GA 911CZ UT WOS:000227980403501 ER PT J AU Fu, Y Robinson, MR Ponce, L Yuan, P Wiesner, M Bender, HM Wang, NS Csaky, KG AF Fu, Y Robinson, MR Ponce, L Yuan, P Wiesner, M Bender, HM Wang, NS Csaky, KG TI Inhibition of angiogenesis by an integrin antagonist in chicken choroiallantoic membrane assay from a sustained-release implant SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO 2005) CY MAY 01-05, 2005 CL Ft Lauderdale, FL SP Assoc Res Vision Ophthalmol C1 Univ Maryland, College Pk, MD 20742 USA. NEI, NIH, Bethesda, MD 20892 USA. NIH, Dept Pharm, CC, Bethesda, MD 20892 USA. Merck KGaA, Inst Drug Metab & Pharmacokinet, Darmstadt, Germany. RI Fu, Yingli/B-8057-2012; Wang, Nam Sun/E-4253-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PY 2005 VL 46 SU S MA 3950 PG 1 WC Ophthalmology SC Ophthalmology GA 911CZ UT WOS:000227980404242 ER PT J AU Hooper, LC Lee, MT Detrick, B Hooks, JJ AF Hooper, LC Lee, MT Detrick, B Hooks, JJ TI Induction of adhesion molecules (sE-selectin and sICAM-1) and interferon-beta by human retinal vascular endothelial cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO 2005) CY MAY 01-05, 2005 CL Ft Lauderdale, FL SP Assoc Res Vision Ophthalmol C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PY 2005 VL 46 SU S MA 4201 PG 1 WC Ophthalmology SC Ophthalmology GA 911CZ UT WOS:000227980404495 ER PT J AU Oh, ECT Kjellstrom, S Bush, RA Bennett, J Sieving, PA Swaroop, A AF Oh, ECT Kjellstrom, S Bush, RA Bennett, J Sieving, PA Swaroop, A TI Nrl is sufficient for the differentiation of functional rods SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO 2005) CY MAY 01-05, 2005 CL Ft Lauderdale, FL SP Assoc Res Vision Ophthalmol C1 Univ Michigan, Grad Program Neurosci, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Ophthalmol & Vis Sci, Ann Arbor, MI 48109 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PY 2005 VL 46 SU S MA 3983 PG 1 WC Ophthalmology SC Ophthalmology GA 911CZ UT WOS:000227980404275 ER PT J AU Posner, M Smith, A Vihtelic, TS Wistow, GJ AF Posner, M Smith, A Vihtelic, TS Wistow, GJ TI A second alpha B crystallin from the zebrafish (Danio rerio) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO 2005) CY MAY 01-05, 2005 CL Ft Lauderdale, FL SP Assoc Res Vision Ophthalmol C1 Univ Notre Dame, Notre Dame, IN 46556 USA. Ashland Univ, Dept Biol, Ashland, OH USA. NEI, Sect Mol Struct & Funct Genom, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PY 2005 VL 46 SU S MA 3870 PG 1 WC Ophthalmology SC Ophthalmology GA 911CZ UT WOS:000227980404161 ER PT J AU Sergeev, YV Backlund, PS Soustov, LV Chelnokov, EV Ostrovsky, MA Hejtmancik, JF AF Sergeev, YV Backlund, PS Soustov, LV Chelnokov, EV Ostrovsky, MA Hejtmancik, JF TI Increased UV-Light sensitivity of amino-arm truncated beta A3-crystallin: Specific structural modifications SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO 2005) CY MAY 01-05, 2005 CL Ft Lauderdale, FL SP Assoc Res Vision Ophthalmol C1 NEI, Bethesda, MD 20892 USA. NICHD, Lcmb, Bethesda, MD 20892 USA. Russian Acad Sci, Inst Appl Phys, Nizhnii Novgorod 603600, Russia. NEI, Ogvfb, Nizhnii Novgorod, Russia. Russian Acad Sci, IBP, Moscow, Russia. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PY 2005 VL 46 SU S MA 3878 PG 1 WC Ophthalmology SC Ophthalmology GA 911CZ UT WOS:000227980404168 ER PT J AU Vistica, BP Chen, J Takase, H Ham, DI Wawrousek, EF Egwuagu, CE Chan, CC Gery, I AF Vistica, BP Chen, J Takase, H Ham, DI Wawrousek, EF Egwuagu, CE Chan, CC Gery, I TI Different models of ocular inflammation: Variability in the populations of infiltrating cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO 2005) CY MAY 01-05, 2005 CL Ft Lauderdale, FL SP Assoc Res Vision Ophthalmol C1 NEI, Immunol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. NEI, Mol & Dev Biol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PY 2005 VL 46 SU S MA 969 PG 1 WC Ophthalmology SC Ophthalmology GA 911CZ UT WOS:000227980401005 ER PT J AU Ben-Shabat, S Elmalak, O Nyska, A Domb, AJ AF Ben-Shabat, S Elmalak, O Nyska, A Domb, AJ TI Synthesis and characterization of biodegradable copolyesters and copolyanhydrides prepared from fumaric and succinic acid trimers and oligomers SO ISRAEL JOURNAL OF CHEMISTRY LA English DT Article ID DRUG-CARRIER MATRICES; BIOERODIBLE POLYANHYDRIDES; IN-VIVO; DEGRADATION; DELIVERY; POLYMERS; RELEASE; EROSION AB A series of new biodegradable copolymers and copolyanhydrides built of trimers of fumaric and succinic acid and propylene glycol, covering a wide range of compositions, were prepared and characterized for use as drug carriers. The polymers were found to degrade within a period of weeks. Polyanhydrides loaded with ibuprofen as a model drug released the drug for a period of one week, while the polyesters released the drug for more then 30 days. The biocompatibility and the rate of evacuation of trimer-based polymers of fumaric and succinic acids were investigated in rats. All polymers were found compatible when implanted in mice. C1 Ben Gurion Univ Negev, Dept Pharmacol, Fac Hlth Sci, IL-84105 Beer Sheva, Israel. Ben Gurion Univ Negev, Sch Pharm, Fac Hlth Sci, IL-84105 Beer Sheva, Israel. Hebrew Univ Jerusalem, Dept Med Chem & Nat Prod, Sch Pharm, Fac Med, IL-91120 Jerusalem, Israel. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Ben-Shabat, S (reprint author), Ben Gurion Univ Negev, Dept Pharmacol, Fac Hlth Sci, IL-84105 Beer Sheva, Israel. EM sbs@bou.ac.il NR 20 TC 3 Z9 3 U1 2 U2 2 PU LASER PAGES PUBL LTD PI JERUSALEM PA MERKAZ SAPIR 6/36, GIVAT SHAUL, PO BOX 35409, JERUSALEM 91352, ISRAEL SN 0021-2148 J9 ISRAEL J CHEM JI Isr. J. Chem. PY 2005 VL 45 IS 4 BP 411 EP 420 DI 10.1560/EDR4-8FC1-CQ8M-J6RL PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 988CZ UT WOS:000233570300004 ER PT J AU Zeng, XC Corzo, G Hahin, R AF Zeng, XC Corzo, G Hahin, R TI Scorpion venom peptides without disulfide bridges SO IUBMB LIFE LA English DT Review DE scorpion; venom peptide; antimicrobial; non disulfide-bridged peptide (NDBP); bradykinin-potentiating peptide; intracellular signaling; classification; evolution ID BUTHUS-MARTENSII KARSCH; BRADYKININ-POTENTIATING PEPTIDE; ANGIOTENSIN-CONVERTING ENZYME; ANTIMICROBIAL PEPTIDES; OPISTHACANTHUS-MADAGASCARIENSIS; RECEPTOR; TOXINS; ACTIVATION; EVOLUTION; CHANNELS AB Several hundred disulfide-bridged neurotoxic peptides have been characterized from scorpion venom; however, only few scorpion venom peptides without disulfide bridges have been identified and characterized. These non-disulfide-bridged peptides (NDBPs) are a novel class of molecules because of their unique antimicrobial, immunological or cellular signaling activities. This review provides an overview of their structural simplicity, precursor processing, biological activities and evolution, and sheds insight into their potential clinical and agricultural applications. Based on their pharmacological activities and peptide size similarity, we have classified these peptides into six subfamilies. C1 Wuhan Univ, Coll Life Sci, Inst Virol, Key Lab MOE Virol,Dept Biotechnol, Wuhan 430072, Peoples R China. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Nacl Autonoma Mexico, Inst Biotechnol, Cuernavaca 62210, Morelos, Mexico. No Illinois Univ, Dept Biol Sci, De Kalb, IL 60115 USA. RP Zeng, XC (reprint author), Wuhan Univ, Coll Life Sci, Inst Virol, Key Lab MOE Virol,Dept Biotechnol, Wuhan 430072, Peoples R China. EM zengx@mail.nih.gov OI Corzo, Gerardo/0000-0002-9513-1622 NR 42 TC 80 Z9 92 U1 1 U2 13 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD JAN PY 2005 VL 57 IS 1 BP 13 EP 21 DI 10.1080/15216540500058899 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 920CH UT WOS:000228666000004 PM 16036557 ER PT J AU Magder, LS Mofenson, L Paul, ME Zorrilla, CD Blattner, WA Tuomala, RE LaRussa, P Landesman, S Rich, KC AF Magder, LS Mofenson, L Paul, ME Zorrilla, CD Blattner, WA Tuomala, RE LaRussa, P Landesman, S Rich, KC TI Risk factors for in utero and intrapartum transmission of HIV SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE timing of transmission; vertical transmission; misclassification; secular trends; antiretroviral therapy ID HUMAN-IMMUNODEFICIENCY-VIRUS; TO-CHILD TRANSMISSION; VERTICAL TRANSMISSION; PROSPECTIVE COHORT; GESTATIONAL-AGE; TYPE-1; INFECTION; WOMEN; INTRAUTERINE; ASSOCIATION AB Objective: To identify predictors of in utero and intrapartum HIV-1 transmission in infants born in the Women and Infants Transmission Study between 1990 and 2000. Methods: In utero HIV-1 infection was defined as an infant with the first positive HIV-1 peripheral blood mononuclear cell culture and/or DNA polymerase chain reaction assay at 7 days of age or younger; intrapartum infection was defined as having a negative HIV-1 culture and/or DNA polymerase chain reaction assay at 7 days of age or younger and the first positive assay after 7 days of age. Results: Of 1709 first-born singleton children with defined HIV-1 infection status, 166 (9.7%) were found to be HIV-1 infected; transmission decreased from 18.1% in 1990-1992 to 1.6% in 1999-2000. Presumed in utero infection was observed in 34% of infected children, and presumed intrapartum infection, in 66%. Among infected children, the proportion with in utero infection increased over time from 27% in 1990-1992 to 80% (4 of 5) in 1999-2000 (P = 0.072). Maternal antenatal viral load and antiretroviral therapy were associated with risk of both in utero and intrapartum transmission. Controlling for maternal antenatal viral load and antiretroviral therapy, low birth weight was significantly associated with in utero transmission, while age, antenatal CD4(+) cell percentage, year, birth weight, and duration of membrane rupture were associated with intrapartum transmission. Conclusion: Although there have been significant declines in perinatal HIV-1 infection over time, there has been an increase in the proportion of infections transmitted in utero. C1 Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. NICHHD, Bethesda, MD 20892 USA. Texas Childrens Hosp, Sect Allergy Immunol, Houston, TX 77030 USA. Univ Puerto Rico, Dept Obstet & Gynecol, San Juan, PR 00936 USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Brookdale Hosp, Dept Med, Brooklyn, NY USA. Univ Illinois, Dept Pediat, Chicago, IL USA. RP Magder, LS (reprint author), Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. EM Lmagder@epi.umaryland.edu OI Mofenson, Lynne/0000-0002-2818-9808 FU NCRR NIH HHS [RR000188, RR000645]; NIAID NIH HHS [U01 AI 034841, 1 U01 AI 050274-01, N01 AI 085339, U01 AI 034858]; NICHD NIH HHS [U01 HD 036117, U01 HD 041983]; NIDA NIH HHS [9U01 DA 015054, U01 DA 015053] NR 35 TC 72 Z9 76 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2005 VL 38 IS 1 BP 87 EP 95 DI 10.1097/00126334-200501010-00016 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 885TI UT WOS:000226179400016 PM 15608531 ER PT J AU Elkashef, A Rawson, R Smith, E Pearce, V Campbell, J Carlton, B Gorodetzky, C Haning, W Mawhinney, J McCann, M Pham, T Weis, D Ling, W Vocci, F AF Elkashef, A Rawson, R Smith, E Pearce, V Campbell, J Carlton, B Gorodetzky, C Haning, W Mawhinney, J McCann, M Pham, T Weis, D Ling, W Vocci, F TI Interim analysis results from a phase II trial of bupropion for Methamphetamine dependence SO JOURNAL OF ADDICTIVE DISEASES LA English DT Meeting Abstract C1 NIDA, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Integrated Substance Abuse Programs, Los Angeles, CA 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 2005 VL 24 IS 2 MA 12A BP 120 EP 120 PG 1 WC Substance Abuse SC Substance Abuse GA 919JP UT WOS:000228614600021 ER PT J AU James, SP AF James, SP TI Prototypic disorders of gastrointestinal mucosal immune function: Celiac disease and Crohn's disease SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Celiac disease; Crohn's disease; mucosal immunity; tolerance ID INFLAMMATORY-BOWEL-DISEASE; GENETIC-VARIATION; STRUCTURAL BASIS; RESPONSES; PEPTIDES; GLUTENIN; CHILDREN; GLIADIN; SPRUE AB Celiac disease is a disorder of the small intestine characterized by chronic inflammation of the mucosa and protean clinical manifestations caused by loss of tolerance to dietary antigens. Two strongly associated cofactors have been identified: the presence of HLA-DQ2 or HLA-DQ8 in the host and specific antigenic peptides in the diet that are present in wheat, rye, and barley. Most patients have complete remission after dietary elimination of these foods. Crohn's disease is characterized by chronic, relapsing, recurrent, focal, transmural inflammation of the gastrointestinal tract that can lead to multiple serious problems requiring chronic medical and surgical therapy. Crohn's disease is associated with multiple genetic mutations, at least one of which has been clearly implicated in innate immunity. Multiple lines of evidence suggest that the disease involves abnormal immune responses to gut microbial flora. C1 NIDDK, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. RP James, SP (reprint author), NIDDK, Div Digest Dis & Nutr, 6707 Democracy Blvd,Room 677, Bethesda, MD 20892 USA. EM Jamess@EXTRA.NIDDK.NIH.gov NR 24 TC 22 Z9 24 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2005 VL 115 IS 1 BP 25 EP 30 DI 10.1016/j.jaci.2004.11.011 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 886XS UT WOS:000226267000003 PM 15637543 ER PT J AU Kan, H Birkle, D Jain, AC Failinger, C Xie, S Finkel, MS AF Kan, H Birkle, D Jain, AC Failinger, C Xie, S Finkel, MS TI p38 MAP kinase inhibitor reverses stress-induced cardiac myocyte dysfunction SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE adult rat ventricular myocyte; mitogen-activated protein kinase ID CONGESTIVE-HEART-FAILURE; ACTIVATED PROTEIN-KINASES; BETA-ADRENERGIC-RECEPTOR; N-TERMINAL KINASES; PRENATAL STRESS; DEPRESSION; CARDIOMYOCYTES; INVOLVEMENT; ISCHEMIA; SIGNAL AB Stress is gaining increasing acceptance as an independent risk factor contributing to adverse cardiovascular outcomes. Potential mechanisms responsible for the deleterious effects of stress on the development and progression of cardiovascular disease remain to be elucidated. An established animal model of stress in humans is the prenatally stressed (PS) rat. We stressed rats in their third trimester of pregnancy by daily injections of saline and moving from cage to cage. Male offspring of these stressed dams (PS) and age-matched male control offspring (control) were further subjected to restraint stress (R) at 6 and 7 wk of age. Echocardiography revealed a significant decrease in fractional shortening in PS + R vs. controls +R (45.8 +/- 3.9 vs. 61.9 +/- 2.4%, PS + R vs. controls + R; P < 0.01; n = 12). Isolated adult rat ventricular myocytes from PS + R also revealed diminished fractional shortening (6.7 +/- 0.8 vs. 12.7 +/- 1.1%, PS + R vs. controls + R; P < 0.01; n = 24) and blunted inotropic responses to isoproterenol (P < 0.01; n = 24) determined by automated border detection. The p38 mitogen-activated protein ( MAP) kinase inhibitor SB-203580 blocked p38 MAP kinase phosphorylation, reversed the depression in fractional shortening, and partially ameliorated the blunted adrenergic signaling seen in adult rat ventricular myocytes from PS + R. Phosphorylation of p38 MAP kinase in cardiac myocytes by stress may be sufficient to lead to myocardial dysfunction in animal models and possibly humans. C1 W Virginia Univ, Sch Med, Dept Med, Morgantown, WV 26506 USA. W Virginia Univ, Sch Med, Dept Physiol & Pharmacol, Morgantown, WV 26506 USA. NIH, Natl Ctr Complimentary & Alternat Med, Bethesda, MD USA. Louis A Johnson Vet Affairs Med Ctr, Clarksburg, WV USA. RP Finkel, MS (reprint author), WVU Cardiol, Dept Med, Med Ctr Dr, Morgantown, WV 26506 USA. EM mfinkel@hsc.wvu.edu FU NHLBI NIH HHS [R01 HL 70565] NR 32 TC 10 Z9 10 U1 1 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. PD JAN PY 2005 VL 98 IS 1 BP 77 EP 82 DI 10.1152/japplphysiol.00171.2004 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 878PM UT WOS:000225658900009 PM 15465893 ER PT J AU Walsh, S Zmuda, JM Cauley, JA Shea, PR Metter, EJ Hurley, BF Ferrell, RE Roth, SM AF Walsh, S Zmuda, JM Cauley, JA Shea, PR Metter, EJ Hurley, BF Ferrell, RE Roth, SM TI Androgen receptor CAG repeat polymorphism is associated with fat-free mass in men SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE body composition; genetics; muscle mass; muscle strength; testosterone ID BONE-MINERAL DENSITY; MUSCLE STRENGTH; SKELETAL-MUSCLE; TRINUCLEOTIDE REPEATS; GENETIC INFLUENCES; BREAST-CANCER; ELDERLY-MEN; HEALTHY-MEN; WOMEN; AGE AB The human androgen receptor (AR) gene contains a CAG ( glutamine) repeat polymorphism in exon 1 that is inversely associated with transcriptional activity of the AR. We studied the association of AR CAG repeat length, fat-free mass (FFM), and testosterone in two independent cohorts: 294 Caucasian men, aged 55 - 93 yr, from the Study of Osteoporotic Risk in Men ( STORM), and 202 Caucasian volunteers ( 112 men and 90 women), aged 19 - 90 yr, from the Baltimore Longitudinal Study of Aging ( BLSA). Subjects were genotyped to determine the number of AR CAG repeats and grouped as carrying either < 22 or &GE; 22 repeats. Whole body soft tissue composition was measured by dual-energy X-ray absorptiometry. Men with greater CAG repeat number exhibited significantly greater total FFM than those with fewer CAG repeats in both cohorts (STORM: 59.2 +/- 0.3 vs. 58.0 +/- 0.4 kg, P = 0.02; BLSA: 57.2 +/- 1.1 vs. 53.8 +/- 1.1 kg, P = 0.04). Similar results were observed for total FFM normalized to height. No differences were seen in women in the BLSA cohort. In the BLSA cohort, serum testosterone levels were higher in subjects with greater repeat number ( P = 0.003). This same pattern approached significance in the STORM cohort ( P = 0.07). In conclusion, the androgen receptor CAG repeat polymorphism is associated with FFM in men in two independent cohorts. Additional studies are needed to confirm this observation and to clarify the mechanisms involved. C1 Univ Maryland, Dept Kinesiol, Coll Hlth & Human Performance, College Pk, MD 20742 USA. NIA, Clin Res Branch, Baltimore, MD 21224 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA USA. RP Roth, SM (reprint author), Univ Maryland, Dept Kinesiol, Coll Hlth & Human Performance, 2134 HHP Bldg, College Pk, MD 20742 USA. EM sroth1@umd.edu RI Cauley, Jane/N-4836-2015; OI Cauley, Jane/0000-0003-0752-4408; Shea, Patrick/0000-0001-6804-5131; Roth, Stephen/0000-0002-7841-3695 FU NIA NIH HHS [R01 AG021500-01A1, AG 21500, AG 22791, K01 AG022791, L30 AG024705, L30 AG024705-02, L30 AG024705-03, R01 AG021500, R01 AG021500-02]; NIAMS NIH HHS [AR 35582, P60 AR 44811]; NIDDK NIH HHS [DK 46204] NR 49 TC 72 Z9 81 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JAN PY 2005 VL 98 IS 1 BP 132 EP 137 DI 10.1152/japplphysiol.00537.2004 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 878PM UT WOS:000225658900016 PM 15377647 ER PT J AU Manini, T Sagendorf, K Mayer, J Ploutz-Snyder, L AF Manini, T Sagendorf, K Mayer, J Ploutz-Snyder, L TI Trunk extensor muscle function in young and old women: A pilot study SO JOURNAL OF BACK AND MUSCULOSKELETAL REHABILITATION LA English DT Article; Proceedings Paper CT 47th Annual Meeting American-College-of-Sports-Medicine CY MAY 31-JUN 03, 2000 CL INDIANAPOLIS, IN SP Amer Coll Sports Med DE aging; muscle strength; muscle endurance; low back endurance; trunk extensors ID LOW-BACK-PAIN; STRENGTH; AGE; MEN; ENDURANCE; EXERCISE; GENDER; LUMBAR; MASS; DETERMINANTS AB The purpose of this study was to document age-related alterations in trunk extensor strength and to compare these to changes in knee extensor strength over varying angles of muscle contraction. A secondary purpose was to compare age-related changes in trunk extensor endurance while statistically correcting for torso mass differences. Eighteen older (70 +/- 7.3 years) and fifteen younger (22.1 +/- 4.6 years) women volunteered for the study. Torso mass and trunk extension endurance (Modified-Sorenson test) were also evaluated. The results suggested that age-related torque production was both angle and muscle group dependent. Younger adults were 29% stronger in the knee and 23% stronger in the trunk extensors. Furthermore, the difference between age groups in knee extensor strength was 2.30 Nm/kg at 78 degrees, but only 0.47 Nm/kg at 6 degrees of knee flexion. This angle discrepancy was not evident in the trunk extensors. Following torso mass correction, trunk extension endurance time did not differ between ages (Young: 160.4 +/- 65.8 vs. Old: 159.5 +/- 71.9 sec, p = 0.99). Our study suggests that the elderly should focus on improving trunk extension strength rather than endurance. Also, knee extensor strength exercises should be emphasized between 60 degrees and 108 degrees of knee flexion in the elderly to combat the age-related loss of lower extremity strength. C1 Syracuse Univ, Dept Exercise Sci, Musculoskeletal Lab, Syracuse, NY 13244 USA. US Spine & Sport Fdn, San Diego, CA USA. RP Manini, T (reprint author), NIA, Gateway Bldg Suite 3C309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM manint@mail.nih.gov NR 35 TC 1 Z9 1 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8127 J9 J BACK MUSCULOSKELET JI J. Back Musculoskelet. Rehabil. PY 2005 VL 18 IS 1-2 BP 5 EP 13 PG 9 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 979JA UT WOS:000232937000002 ER PT J AU Itoh, Y Wang, X Hinnebusch, BJ Preston, JF Romeo, T AF Itoh, Y Wang, X Hinnebusch, BJ Preston, JF Romeo, T TI Depolymerization of beta-1,6-N-acetyl-D-glucosamine disrupts the integrity of diverse bacterial biofilms SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; STAPHYLOCOCCUS-EPIDERMIDIS; INTERCELLULAR-ADHESION; GENETIC-ANALYSIS; YERSINIA-PESTIS; POLYSACCHARIDE; LOCUS; EXOPOLYSACCHARIDE; SURFACES; PROTEIN AB Polymeric beta-1,6-N-acetyl-D-glucosamine (poly-beta-1,6-GlcNAc) has been implicated as an Escherichia coli and Staphylococcus epidermidis biofilm adhesin, the formation of which requires the pgaABCD and icaABCD loci, respectively. Enzymatic hydrolysis of poly-beta-1,6-GlcNAc, demonstrated for the first time by chromatography and mass spectrometry, disrupts biofilm formation by these species and by Yersinia pestis and Pseudomonas fluorescens, which possess pgaABCD homologues. C1 Emory Univ, Sch Med, Dept Microbiol & Immunol, Rollins Res Ctr 3105, Atlanta, GA 30322 USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA. Univ Florida, Dept Microbiol & Cell Sci, Gainesville, FL 32611 USA. RP Romeo, T (reprint author), Emory Univ, Sch Med, Dept Microbiol & Immunol, Rollins Res Ctr 3105, 1510 Clifton Rd NE, Atlanta, GA 30322 USA. EM romeo@microbioemory.edu FU NCRR NIH HHS [1S10 RR 14645-01]; NIGMS NIH HHS [GM066794, R01 GM066794] NR 38 TC 160 Z9 170 U1 0 U2 16 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 2005 VL 187 IS 1 BP 382 EP 387 DI 10.1128/JB.187.1.382-387.2005 PG 6 WC Microbiology SC Microbiology GA 888QX UT WOS:000226390400041 PM 15601723 ER PT J AU Bonner, MR Alavanja, MCR AF Bonner, MR Alavanja, MCR TI The Agricultural Health Study Biomarker Workshop on Cancer Etiology - Introduction: Overview of study design, results, and goals of the workshop SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Editorial Material ID LONG-EVANS RAT; PESTICIDE APPLICATORS; ALACHLOR; NEOPLASMS; COHORT; RISK C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. RP Bonner, MR (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. EM bonnerm@mail.nih.gov NR 11 TC 0 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2005 VL 19 IS 3 BP 169 EP 171 DI 10.1002/jbt.20070 PG 3 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 943LE UT WOS:000230354300005 PM 15977198 ER PT J AU Vermeulen, R De Roos, AJ Bakke, B Blair, A Hildesheim, A Pinto, L Gillette, PP Lynch, CF Allen, RH Alavanja, MC AF Vermeulen, R De Roos, AJ Bakke, B Blair, A Hildesheim, A Pinto, L Gillette, PP Lynch, CF Allen, RH Alavanja, MC TI A study on immunological responses to exposures encountered in corn farming SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. NCI, HPV Monitoring Lab, Frederick, MD 21702 USA. Univ Iowa, Coll Publ Hlth, Iowa City, IA 52242 USA. US EPA, Washington, DC 20460 USA. RP Vermeulen, R (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM vermeulr@mail.nih.gov RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 NR 0 TC 5 Z9 5 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2005 VL 19 IS 3 BP 172 EP 172 DI 10.1002/jbt.20071 PG 1 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 943LE UT WOS:000230354300006 PM 15977189 ER PT J AU Moore, LE Pfeiffer, R Warner, M Clark, M Skibola, C Steinmous, C Alguacil, J Rothman, N Smith, MT Smith, AH AF Moore, LE Pfeiffer, R Warner, M Clark, M Skibola, C Steinmous, C Alguacil, J Rothman, N Smith, MT Smith, AH TI Identification of biomarkers of arsenic exposure and metabolism in urine using SELDI technology SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article C1 NCI, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA. RP Moore, LE (reprint author), NCI, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA. EM moorele@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011; Smith, Allan/F-9249-2011 NR 0 TC 7 Z9 7 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2005 VL 19 IS 3 BP 176 EP 176 DI 10.1002/jbt.20074 PG 1 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 943LE UT WOS:000230354300009 PM 15977200 ER PT J AU Kunkel, TA AF Kunkel, TA TI DNA replication and repair reactions relevant to the AHS SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article C1 NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. EM kiinkel@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2005 VL 19 IS 3 BP 190 EP 191 DI 10.1002/jbt.20082 PG 2 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 943LE UT WOS:000230354300015 PM 15977194 ER PT J AU Alavanja, MCR Bonner, MR Furlong, CE Allen, R Hodgson, E AF Alavanja, MCR Bonner, MR Furlong, CE Allen, R Hodgson, E TI Molecular Biomarker Workshop - Agricultural Health Study - Discussion and conclusions SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Genome Sci, Seattle, WA USA. N Carolina State Univ, Dept Toxicol, Raleigh, NC 27695 USA. RP Alavanja, MCR (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. EM alavanjm@exchange.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2005 VL 19 IS 3 BP 192 EP 193 DI 10.1002/jbt.20083 PG 2 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 943LE UT WOS:000230354300016 PM 15977186 ER PT J AU Sviridov, A Chernomordik, V Hassan, M Russo, A Eidsath, A Smith, P Gandjbakhche, AH AF Sviridov, A Chernomordik, V Hassan, M Russo, A Eidsath, A Smith, P Gandjbakhche, AH TI Intensity profiles of linearly polarized light backscattered from skin and tissue-like phantoms SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE light propagation in tissue; equi-intensity profiles of light; collagen fiber orientation; optical diagnosis; fibrosis ID OPTICAL-PROPERTIES; PHOTON MIGRATION; SCATTERING MEDIA; REFLECTANCE; PROPAGATION; ANISOTROPY; MODEL; TRANSMITTANCE; PARAMETER; PATTERNS AB Anisotropy of mouse and human skin is investigated in vivo using polarized videoreflectometry. An incident beam (linearly polar-wavelength 650 nm) is focused at the sample surface. Two types of tissuelike media are used as controls to verify the technique: isotropic delrin and highly anisotropic demineralized bone with a priori knowledge of preferential orientation of collagen fibers. Equi-intensity profiles of light, backscattered from the sample, are fitted with ellipses that appear to follow the orientation of the collagen fibers. The ratio of the ellipse semiaxes is well correlated with the ratio of reduced scattering coefficients obtained from radial intensity distributions. Variation of equi-intensity profiles with distance from the incident beam is analyzed for different initial polarization states of the light and the relative orientation of polarization filters for incident and backscattered light. For the anisotropic media (demineralized bone and human and mouse skin), a qualitative difference between intensity distributions for cross- and co-polarized orientations of the polarization analyzer is observed up to a distance of 1.5 to 2.5 mm from the entry point. The polarized videoreflectometry of the skin may be a useful tool to assess skin fibrosis resulting from radiation treatment. (c) 2005 Society of Photo-Optical Instrumentation Engineers. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Russian Acad Sci, Inst Laser & Informat Technol, Troitsk 142190, Moscow Region, Russia. NCI, NIH, Radiat Biol Branch, Bethesda, MD 20892 USA. Natl Inst Hlth, Off Res Serv, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. RP Chernomordik, V (reprint author), NICHHD, NIH, Bldg 12A,Rm 2041,9000 Rockville Pike, Bethesda, MD 20892 USA. EM vchern@helix.nih.gov NR 32 TC 27 Z9 28 U1 0 U2 7 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS 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-FEB PY 2005 VL 10 IS 1 AR 014012 DI 10.1117/1.1854677 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 927PZ UT WOS:000229208100027 PM 15847593 ER PT J AU Kibler, KV Jeang, KT AF Kibler, KV Jeang, KT TI Human T-cell leukemia virus type I: 25 years of progress and challenges SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Review ID MITOTIC SPINDLE CHECKPOINT; NF-KAPPA-B; HTLV-I; FUNCTIONAL IMPAIRMENT; CYCLE PROGRESSION; TAX ONCOPROTEIN; EXPRESSION; PROTEIN; P53; MYELOPATHY C1 NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. Arizona State Univ, Ctr Infect Dis & Vaccinol, Tempe, AZ 85287 USA. RP Jeang, KT (reprint author), NIAID, Mol Microbiol Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 50 TC 2 Z9 5 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PY 2005 VL 12 IS 1 BP 7 EP 11 DI 10.1007/s11373-004-8164-x PG 5 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 926WX UT WOS:000229155500001 PM 15864735 ER PT J AU McFeeters, R Fowler, C Gaponenko, V Byrd, R AF McFeeters, R Fowler, C Gaponenko, V Byrd, R TI Efficient and precise measurement of H-alpha-C-alpha, C-alpha-C ', C-alpha-C-beta and H-N-N residual dipolar couplings from 2D H-N-N correlation spectra SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE J-coupling; J-modulation; residual dipolar coupling; semi-constant time ID MAGNETIC-FIELD DEPENDENCE; 2-DIMENSIONAL NMR-SPECTRA; ONE-BOND; ORIENTED MACROMOLECULES; POLYACRYLAMIDE GELS; DOMAIN ORIENTATION; BINDING PROTEIN; PULSE SCHEME; ALIGNMENT; N-15 AB A suite of experiments are presented for the measurement of H-alpha-C-alpha, C-alpha-C', C-alpha-C-beta and H-N-N couplings from uniformly N-15, C-13 labeled proteins. Couplings are obtained from a series of intensity modulated two-dimensional H-N-N spectra equivalent to the common H-1-N-15-HSQC spectra, alleviating many overlap and assignment issues associated with other techniques. To illustrate the efficiency of this method, H-alpha-C-alpha, C-alpha-C', and H-N-N isotropic scalar couplings were determined for ubiquitin from data collected in less than 4.5 h, C-alpha-C-beta data collection required 10 h. The resulting couplings were measured with an average error of +/-0.06, +/-0.05, +/-0.04 and +/-0.10 Hz, respectively. This study also shows H-alpha-C-alpha and C-alpha-C-beta couplings, valuable because they provide orientation of bond vectors outside the peptide plane, can be measured in a uniform and precise way. Superior accuracy and precision to existing 3D measurements for C-alpha-C' couplings and increased precision compared to IPAP measurements for H-N-N couplings are demonstrated. Minor modi. cations allow for acquisition of modulated H-N-C' 2D spectra, which can yield additional well resolved peaks and significantly increase the number of measured RDCs for proteins with crowded H-1-N-15 resonances. C1 NCI, Macromol NMR Sect, Struct Biophys Lab, Frederick, MD 21702 USA. RP Byrd, R (reprint author), NCI, Macromol NMR Sect, Struct Biophys Lab, Frederick, MD 21702 USA. EM rabyrd@ncifcrf.gov RI Byrd, R. Andrew/F-8042-2015; OI Byrd, R. Andrew/0000-0003-3625-4232; Fowler, Andrew/0000-0001-5646-5307 NR 41 TC 19 Z9 19 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD JAN PY 2005 VL 31 IS 1 BP 35 EP 47 DI 10.1007/s10858-004-6057-y PG 13 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 896NG UT WOS:000226940200004 PM 15692737 ER PT J AU Lee, HS Gruschus, JM Zhang, T Ferretti, JA AF Lee, HS Gruschus, JM Zhang, T Ferretti, JA TI NMR assignments of the DNA-bound human Csx/Nkx2.5 homeodomain and NK2-specific domain SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE heteronuclear NMR; homeodomain (HD); NK2-specific domain (NK2-SD); NMR resonance assignment ID TRANSCRIPTIONAL ACTIVITY; IDENTIFICATION; NKX-2.5 C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Ferretti, JA (reprint author), NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. EM ferrettj@nhlbi.nih.gov NR 9 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD JAN PY 2005 VL 31 IS 1 BP 75 EP 76 PG 2 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 896NG UT WOS:000226940200013 PM 15692746 ER PT J AU Proschan, MA AF Proschan, MA TI Two-stage sample size re-estimation based on a nuisance parameter: A review SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE adaptive methods; ancillary statistic; blinding; continuous outcome; clinical trials; conditioning; correlation; dichotomous outcome; independence; internal pilot study; lumping; pooling; power; restricted design; unrestricted design ID I ERROR RATE; CLINICAL-TRIALS; ASYMPTOTIC THEORY; T-TEST; VARIANCE AB Sample size calculations are important and difficult in clinical trails because they depend on the nuisance parameter and treatment effect. Recently, much attention has been focused on two-stage methods whereby the first stage constitutes an internal pilot study used to estimate parameters and revise the final sample size. This paper reviews two-stage methods based on estimation of nuisance parameters in either a continuous or dichotomous outcome setting. C1 NHLBI, Bethesda, MD 20892 USA. RP Proschan, MA (reprint author), NHLBI, 6701 Rockledge Dr,Room 8222,MSC 7938, Bethesda, MD 20892 USA. EM ProschaM@mail.nih.gov NR 21 TC 41 Z9 41 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2005 VL 15 IS 4 BP 559 EP 574 DI 10.1081/BIP-200063852 PG 16 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 024YO UT WOS:000236232700003 PM 16022163 ER PT J AU Proschan, MA Leifer, E Liu, Q AF Proschan, MA Leifer, E Liu, Q TI Adaptive regression SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE analysis of covariance (ANCOVA); blinding; clinical trials; conditioning; correlation; covariate adjustment; mean squared error (MSE); permutation tests; precision; stepwise regression; stratified randomization AB Adjustment for prognostic covariates is recommended in clinical trials because relative to a t-test, it improves precision and adjusts for treatment imbalances caused by an "unlucky" randomization. But, inclusion of too many covariates can be counterproductive. In the quest to strike a balance between inclusion of all important variables and not going overboard, people have proposed methods such as stepwise regression, whereby the decision to include a covariate depends on post-randomization data. Covariate inclusion decisions are typically based on either the strength of its correlation with the outcome or the degree of treatment imbalance. Are these methods valid? Is there a valid way to analyze such data? These are some of the questions we address. C1 NHLBI, Bethesda, MD 20892 USA. Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. RP Proschan, MA (reprint author), 6701 Rockledge Dr,Room 8222,MSC 7938, Bethesda, MD 20892 USA. EM ProschaM@mail.nih.gov NR 8 TC 3 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2005 VL 15 IS 4 BP 593 EP 603 DI 10.1081/BIP-200062861 PG 11 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 024YO UT WOS:000236232700005 PM 16022165 ER PT J AU Guo, HY Liu, AY AF Guo, HY Liu, AY TI A simple and efficient bias-reduced estimator of response probability following a group sequential phase II trial SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE bias-reduction; minimum variance unbiased estimation; response rate; sample proportion; Simon's two-stage designs; Whitehead's bias-adjusted estimator ID CLINICAL-TRIALS; DESIGNS AB A phase II clinical trial evaluating the rate of response of a new therapeutic treatment is often designed to have one or two interim analyses, allowing possible termination of the trial at an early stage if lack of treatment efficacy is evident. Due to the sequential nature of such a trial, the sample proportion yields biased estimation for the rate of response. In this paper we propose an estimator of response rate by subtracting the estimated bias directly from the sample proportion. The proposed estimator is simple, intuitive, and easy to compute. When the bias of the sample proportion is of concern to the investigators, the proposed estimator is an efficient alternative to other estimators in the literature in terms of bias and mean squared error. C1 NICHHD, DHHS, Biometry & Math Stat Branch, DESPR, Rockville, MD 20852 USA. Thomas Jefferson High Sch Sci & Technol, Alexandria, VA USA. RP Liu, AY (reprint author), NICHHD, DHHS, Biometry & Math Stat Branch, DESPR, 6100 Execut Blvd, Rockville, MD 20852 USA. EM Liua@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082 NR 12 TC 5 Z9 5 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2005 VL 15 IS 5 BP 773 EP 781 DI 10.1081/BIP-200067771 PG 9 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 024YR UT WOS:000236233000002 PM 16078384 ER PT J AU Chaplet, M Waltregny, D Detry, C Fisher, LW Castronovo, V Bellahcene, A AF Chaplet, M Waltregny, D Detry, C Fisher, LW Castronovo, V Bellahcene, A TI Dentin sialophosphoprotein expression correlates with progression markers in human prostate cancer SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 4th North American Symposium on Skeleted Complications of Malignancy CY APR 28-30, 2005 CL Bethesda, MD SP Natl Inst Hlth C1 Univ Liege, Metastasis Res Lab, Liege, Belgium. NIDCR, Craniofacial & Skeletal Dis Branch, NIH, DHHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PY 2005 VL 20 SU 2 BP P45 EP P45 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 017JT UT WOS:000235690600084 ER PT J AU Koblinski, J VanOsdol, S Kaplan-Singer, B Hossain, R Yokoyama, F Nomizu, M Kleinman, HK Engbring, JA AF Koblinski, J VanOsdol, S Kaplan-Singer, B Hossain, R Yokoyama, F Nomizu, M Kleinman, HK Engbring, JA TI A laminin-alpha 1 peptide, AG73, increases breast cancer bone metastasis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 4th North American Symposium on Skeleted Complications of Malignancy CY APR 28-30, 2005 CL Bethesda, MD SP Natl Inst Hlth C1 NIDCR, Bethesda, MD USA. Tokyo Univ Pharm & Life Sci, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PY 2005 VL 20 SU 2 BP P32 EP P33 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 017JT UT WOS:000235690600059 ER PT J AU Shaughnessy, J Tian, E Qiang, Y Zhan, F Yaccoby, S Zangari, M Tricot, G Barlogie, B Rudikoff, S AF Shaughnessy, J Tian, E Qiang, Y Zhan, F Yaccoby, S Zangari, M Tricot, G Barlogie, B Rudikoff, S TI Toward elucidation of the role of altered Wnt signaling in myeloma and development of corresponding therapeutic interventions SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 4th North American Symposium on Skeleted Complications of Malignancy CY APR 28-30, 2005 CL Bethesda, MD SP Natl Inst Hlth C1 Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PY 2005 VL 20 SU 2 BP P12 EP P13 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 017JT UT WOS:000235690600026 ER PT J AU Yin, J Oberst, M Chock, M Ward, Y Kelly, K AF Yin, J Oberst, M Chock, M Ward, Y Kelly, K TI Ras activation promotes prostate cancer metastasis to bone and brain SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 4th North American Symposium on Skeleted Complications of Malignancy CY APR 28-30, 2005 CL Bethesda, MD SP Natl Inst Hlth C1 NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PY 2005 VL 20 SU 2 BP P39 EP P40 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 017JT UT WOS:000235690600072 ER PT J AU Syed, MA Paterson, DI Ingkanisorn, WP Rhoads, KL Hill, J Cannon, RO Arai, AE AF Syed, MA Paterson, DI Ingkanisorn, WP Rhoads, KL Hill, J Cannon, RO Arai, AE TI Reproducibility and inter-observer variability of dobutamine stress CMR in patients with severe coronary disease: implications for clinical research SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE dobutamine stress test; magnetic resonance imaging; reproducibility; inter-observer variability ID MYOCARDIAL-ISCHEMIA; ARTERY DISEASE; ECHOCARDIOGRAPHY; EXERCISE; INFUSION AB Purpose. The purpose of this study was to analyze reproducibility and inter-observer variability of dobutamine stress cardiac magnetic resonance imaging (dobutamine CMR) and its implications on serial studies. Methods. Nineteen consecutive patients underwent two dobutamine CMR each (median 12 days apart), as part of eligibility criteria for phase I/II stein cell therapy trial. These patients had Canadian Cardiovascular Society Class III/IV angina despite maximal therapy. The two studies were compared for reproducibility of stress response. To assess inter-observer variability, 29 randomly selected dobutamine CMR studies were analyzed by three experienced observers and Kappa values were computed to measure the agreement. Results. Dobutamine CMR studies were completed Without any major complications. The left ventricular function, dobutamine and atropine dose, hemodynamic response, symptomatic response and the results of wall motion and perfusion abnormalities were highly reproducible between the two Studies (p = .91). Sample size calculations Suggested that a clinical trial using dobutamine CMR to detect an endpoint of resolution Of two ischemic segments would require a sample size of 20 subjects and to detect an improvement in perfusion of two segments would require a sample size of 8 subjects. Inter-observer variability between individual and consensus interpretation of dobutamine CMR was good to very good (kappa = 0.81 for wall motion and 0.70 for perfusion). Conclusion. Dobutamine CMR is a highly reproducible technique with very good inter-observer variability and could be used as a specific endpoint in a relatively small clinical trial. C1 NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NHLBI, Cardiovasc Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Arai, AE (reprint author), NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, Bldg 10,Room B1D 416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA. EM araia@nih.gov FU Intramural NIH HHS NR 13 TC 20 Z9 21 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1097-6647 J9 J CARDIOV MAGN RESON JI J. Cardiov. Magn. Reson. PY 2005 VL 7 IS 5 BP 763 EP 768 DI 10.1080/10976640500287414 PG 6 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 989HN UT WOS:000233663600004 PM 16353436 ER PT J AU Holmbeck, K Bianco, P Pidoux, I Inoue, S Billinghurst, RC Wu, W Chrysovergis, K Yamada, S Birkedal-Hansen, H Poole, AR AF Holmbeck, K Bianco, P Pidoux, I Inoue, S Billinghurst, RC Wu, W Chrysovergis, K Yamada, S Birkedal-Hansen, H Poole, AR TI The metalloproteinase MT1-MMP is required for normal development and maintenance of osteocyte processes in bone SO JOURNAL OF CELL SCIENCE LA English DT Article DE bone; osteocytes processes; membrane-type matrix metalloproteinase 1; MMP-13; collagen cleavage ID 3-DIMENSIONAL EXTRACELLULAR-MATRIX; GAP-JUNCTIONS; GELATINASE-A; II COLLAGEN; UP-REGULATION; CELL; DIFFERENTIATION; EXPRESSION; CARTILAGE; CLEAVAGE AB The osteocyte is the terminally differentiated state of the osteogenic mesenchymal progenitor immobilized in the bone matrix. Despite their numerical prominence, little is known about osteocytes and their formation. Osteocytes are physically separated in the bone matrix but seemingly compensate for their seclusion from other cells by maintaining an elaborate network of cell processes through which they interact with other osteocytes and bone-lining cells at the periosteal and endosteal surfaces of the bone. This highly organized architecture suggests that osteocytes make an active contribution to the structure and maintenance of their environment rather than passively submitting to random embedding during bone growth or repair. The most abundant matrix protein in the osteocyte environment is type-I collagen and we demonstrate here that, in the mouse, osteocyte phenotype and the formation of osteocyte processes is highly dependent on continuous cleavage of type-I collagen. This collagenolytic activity and formation of osteocyte processes is dependent on matrix metalloproteinase activity. Specifically, a deficiency of membrane type-I matrix metalloproteinase leads to disruption of collagen cleavage in osteocytes and ultimately to the loss of formation of osteocyte processes. Osteocytogenesis is thus an active invasive process requiring cleavage of collagen for maintenance of the osteocyte phenotype. C1 Natl Inst Dent & Craniofacial Res, Matrix Metalloproteinase Unit, Bethesda, MD 20892 USA. Univ Roma La Sapienza, I-00161 Rome, Italy. Shriners Hosp Children, Joint Dis Lab, Montreal, PQ H3G 1A6, Canada. McGill Univ, Fac Med, Dept Surg, Montreal, PQ H3G 1A6, Canada. McGill Univ, Fac Med, Dept Med, Montreal, PQ H3G 1A6, Canada. McGill Univ, Fac Med, Dept Cell Biol Anat, Montreal, PQ H3G 1A6, Canada. RP Birkedal-Hansen, H (reprint author), Natl Inst Dent & Craniofacial Res, Matrix Metalloproteinase Unit, Bethesda, MD 20892 USA. EM hbhansen@dir.nidcr.nih.gov NR 48 TC 105 Z9 115 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 1 PY 2005 VL 118 IS 1 BP 147 EP 156 DI 10.1242/jcs.01581 PG 10 WC Cell Biology SC Cell Biology GA 896JX UT WOS:000226931500015 PM 15601659 ER PT J AU Kielmanowicz, MG Laham, N Coligan, JE Lemonnier, FO Ehrlich, R AF Kielmanowicz, MG Laham, N Coligan, JE Lemonnier, FO Ehrlich, R TI Mouse HFE inhibits Tf-uptake and iron accumulation but induces non-transferrin bound iron (NTBI)-uptake in transformed mouse fibroblasts SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CELL-SURFACE EXPRESSION; HEREDITARY HEMOCHROMATOSIS PROTEIN; HIGHLY ONCOGENIC ADENOVIRUS-12; CLASS-I; HELA-CELLS; DUODENAL EXPRESSION; KNOCKOUT MOUSE; WILD-TYPE; RECEPTOR AB Iron-uptake and storage are tightly regulated to guarantee sufficient iron for essential cellular processes and to prevent the production of damaging free radicals. A non-classical class I MHC molecule, the hemochromatosis factor (HFE), has been shown to regulate iron metabolism, potentially via its interaction with the transferrin receptor. Whereas, the effect of human HFE (hHFE) on transferrin/transferrin receptor association, as well as on transferrin receptor recycling and the level of cellular iron pools in various cell lines was analyzed, very little is known about the mouse HFE (mHFE) protein. In the following study, our aim waste analyze in more detail the function of mHFE. Surprisingly, we observed that over-expression of mHFE, but not of hHFE, in a mouse transformed cell line, results in a most significant inhibition of transferrin-uptake which correlated with apoptotic cell death. mHFE inhibited transferrin-uptake immediately following transfection and this inhibition persisted in the surviving stable transfectants. Concomitantly, cellular iron derived from transferrin-iron uptake was dramatically limited. The activation of a non-transferrin bound iron-uptake pathway that functions in the stable mHFE-transfected clones could explain their normal growth curves and survival. The hypothesis that iron starvation can induce iron-uptake by a novel transferrin-independent pathway is discussed. (C) 2004 Wiley-Liss, Inc. C1 Tel Aviv Univ, Dept Cell Res & Immunol, George S Wise Fac Life Sci, Tel Aviv, Israel. NIAID, Lab Allerg Dis, NIH, Rockville, MD USA. Inst Pasteur, Unite Immunite Cellulaire Antivirale, Paris, France. RP Ehrlich, R (reprint author), Tel Aviv Univ, Dept Cell Res & Immunol, George S Wise Fac Life Sci, Tel Aviv, Israel. EM rachele@post.tau.ac.il NR 48 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JAN PY 2005 VL 202 IS 1 BP 105 EP 114 DI 10.1002/jcp.20095 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 876RF UT WOS:000225514300011 PM 15389541 ER PT J AU Berezhkovskii, A Szabo, A AF Berezhkovskii, A Szabo, A TI One-dimensional reaction coordinates for diffusive activated rate processes in many dimensions SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID KRAMERS PROBLEM; MODEL; DYNAMICS; REGIME; STATES AB For multidimensional activated rate processes controlled by diffusive crossing of a saddle point region, we show that a one-dimensional reaction coordinate can be constructed even when the diffusion anisotropy is arbitrary. The rate constant, found using the potential of mean force along this coordinate, is identical to that predicted by the multidimensional Kramers-Langer theory. This reaction coordinate minimizes the one-dimensional rate constant obtained using a trial reaction coordinate and is orthogonal to the stochastic separatrix, the transition state that separates reactants from products. (C) 2005 American Institute of Physics. C1 NIH, Ctr Informat Technol, Div Computat Biosci, Math & Stat Comp Lab, Bethesda, MD 20892 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Karpov Inst Phys Chem, Moscow 103064 K64, Russia. RP Berezhkovskii, A (reprint author), NIH, Ctr Informat Technol, Div Computat Biosci, Math & Stat Comp Lab, Bethesda, MD 20892 USA. RI Szabo, Attila/H-3867-2012 NR 28 TC 71 Z9 71 U1 3 U2 25 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD JAN 1 PY 2005 VL 122 IS 1 AR 014503 DI 10.1063/1.1818091 PG 4 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 893DC UT WOS:000226698500037 PM 15638670 ER PT J AU Gopich, I Szabo, A AF Gopich, I Szabo, A TI Theory of photon statistics in single-molecule Forster resonance energy transfer SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID DIFFUSION-INFLUENCED REACTIONS; TRANSFER CONFOCAL MICROSCOPY; FLUORESCENCE SPECTROSCOPY; TIME; DYNAMICS; SIMULATION; PEPTIDES AB We present the theory for the distribution of the number of donor and acceptor photons detected in a time bin and the corresponding energy-transfer efficiency distribution obtained from single-molecule Forster resonance energy-transfer measurements. Photon counts from both immobilized and freely diffusing molecules are considered. Our starting point is the joint distribution for the donor and acceptor photons for a system described by an arbitrary kinetic scheme. This is simplified by exploiting the time scale separation between fast fluorescent transitions and slow processes which include conformational dynamics, intersystem conversion to a dark state, and translational diffusion in and out of the laser spot. The fast fluorescent transitions result in a Poisson distribution of the number of photons which is then averaged over slow fluctuations of the local transfer efficiency and the total number of photons. The contribution of various processes to the distribution and the variance of the energy-transfer efficiency are analyzed.(C) 2005 American Institute of Physics. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Gopich, I (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM gopich@nih.gov RI Szabo, Attila/H-3867-2012 NR 35 TC 105 Z9 105 U1 3 U2 19 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD JAN 1 PY 2005 VL 122 IS 1 AR 014707 DI 10.1063/1.1812746 PG 18 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 893DC UT WOS:000226698500058 PM 15638691 ER PT J AU Tiulpakov, A Rubtsov, P Dedov, I Peterkova, V Bezlepkina, O Chrousos, GP Hochberg, Z AF Tiulpakov, A Rubtsov, P Dedov, I Peterkova, V Bezlepkina, O Chrousos, GP Hochberg, Z TI A novel C-terminal growth hormone receptor (GHR) mutation results in impaired GHR-STAT5 but normal STAT-3 signaling SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID AMINO-ACID SUBSTITUTIONS; BINDING-PROTEIN; SHORT STATURE; INTRACELLULAR DOMAIN; TRUNCATED ISOFORM; TYROSINE RESIDUES; LARON-SYNDROME; GENE; TRANSCRIPTION; SERUM AB GH insensitivity (GHI) is an autosomal recessive disorder caused by defects in the GH receptor (GHR). In a 17-yr-old female with severe short stature and biochemical features of GHI, sequencing of GHR gene revealed a compound heterozygosity for two novel mutations: C83X and a G deletion at position 1776 (1776del). 1776del is predicted to result in GHR truncation to 581 amino acids with a nonsense sequence of residues 560-581. To clarify the effect of 1776del on GHR function, wild-type GHR, GHR-1776del, and two additional GHR mutants, GHR-L561X (stop codon at site of the 1776del) and GHR-I582X (translation termination in GHR-1776del) were transiently expressed in CHO cells. After incubation with recombinant human GH, GHR-1776del showed lower signal transducer and activator of transcription 5 (STAT5)-mediated transcriptional activation (similar to50%, P < 0.05), as well as STAT5 Tyr694 phosphorylation (P < 0.05) compared with wild-type GHR, whereas GHR-L561X and GHR-I582X showed normal STAT5 phosphorylation and transcriptional activity. In contrast, all vectors produced similar effects on STAT3-mediated transcriptional activation. In conclusion, this novel GHR-1776del mutation in a classical GHI patient illustrates an important mechanism of impaired GHR-STAT5 but intact GHR-STAT3 signaling. This effect might result from interference of C-terminal nonsense sequence in mutated GHR with STAT5 docking to upstream tyrosine residues. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Endocrinol Res Ctr, Moscow 115478, Russia. Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. Meyer Childrens Hosp, Rambam Med Ctr, IL-310961 Haifa, Israel. RP Tiulpakov, A (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Suite 9D42, Bethesda, MD 20892 USA. EM tiulpaka@mail.nih.gov RI Dedov, Ivan/D-3729-2014; OI Dedov, Ivan/0000-0002-8175-7886; Bezlepkina, Olga/0000-0001-9621-5732 NR 32 TC 34 Z9 37 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2005 VL 90 IS 1 BP 542 EP 547 DI 10.1210/jc.2003-2133 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 886ME UT WOS:000226230700084 PM 15536163 ER PT J AU Sun, CX Young, HW Molina, JG Volmer, JB Schnermann, J Blackburn, MR AF Sun, CX Young, HW Molina, JG Volmer, JB Schnermann, J Blackburn, MR TI A protective role for the A(1) adenosine receptor in adenosine-dependent pulmonary injury SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DEAMINASE-DEFICIENT MICE; ISCHEMIA-REPERFUSION INJURY; INDUCED BRONCHOCONSTRICTION; MACROPHAGE METALLOELASTASE; IL-13-INDUCED INFLAMMATION; AIRWAY INFLAMMATION; ASTHMATIC SUBJECTS; ALLERGIC RABBITS; GENE-EXPRESSION; PROTEIN-KINASE AB Adenosine is a signaling nucleoside that has been implicated in the regulation of asthma and chronic obstructive pulmonary disease. Adenosine signaling can serve both pro- and anti-inflammatory functions in tissues and cells. In this study we examined the contribution of A(1) adenosine receptor (A(1)AR) signaling to the pulmonary inflammation and injury seen in adenosine deaminase-deficient (ADA-deficient) mice, which exhibit elevated adenosine levels. Experiments revealed that transcript levels for the A(1)AR were elevated in the lungs of ADA-deficient mice, in which expression was localized predominantly to alveolar macrophages. Genetic removal of the A(1)AR from ADA-deficient mice resulted in enhanced pulmonary inflammation along with increased mucus metaplasia and alveolar destruction. These changes were associated with the exaggerated expression of the Th2 cytokines IL-4 and IL-13 in the lungs, together with increased expression of chemokines and matrix metalloproteinases. These findings demonstrate that the A(1)AR plays an anti-inflammatory and/or protective role in the pulmonary phenotype seen in ADA-deficient mice, which suggests that A(1)AR signaling may serve to regulate the severity of pulmonary inflammation and remodeling seen in chronic lung diseases by controlling the levels of important mediators of pulmonary inflammation and damage. C1 Univ Texas, Hlth Sci Ctr, Sch Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA. NIDDK, NIH, Bethesda, MD USA. RP Blackburn, MR (reprint author), Univ Texas, Hlth Sci Ctr, Sch Med, Dept Biochem & Mol Biol, 6431 Fannin St, Houston, TX 77030 USA. EM michael.r.blackburn@uth.tmc.edu OI Blackburn, Michael/0000-0002-1394-9966 FU NHLBI NIH HHS [HL-70952, R01 HL070952]; NIAID NIH HHS [AI-43572, R01 AI043572] NR 57 TC 88 Z9 91 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2005 VL 115 IS 1 BP 35 EP 43 DI 10.1172/JCI200522656 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 890KB UT WOS:000226509000011 PM 15630442 ER PT J AU Kurtzman, CP Robnett, CJ Ward, JM Brayton, C Gorelick, P Walsh, TJ AF Kurtzman, CP Robnett, CJ Ward, JM Brayton, C Gorelick, P Walsh, TJ TI Multigene phylogenetic analysis of pathogenic Candida species in the Kazachstania (Arxiozyma) telluris complex and description of their ascosporic states as Kazachstania bovina sp nov., K-heterogenica sp nov., K-pintolopesii sp nov., and K-slooffiae sp nov. SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID YEASTS; SACCHAROMYCES AB A yeast causing widespread infection of laboratory mice was identified from 26S rRNA gene sequences as Candida pintolopesii. To determine the relationship of C. pintolopesii with other members of the Kazachstania (Arxiozyma) telluris species complex, nucleotide sequences from domains 1 and 2 of the 26S rRNA gene, the mitochondrial small-subunit rRNA gene, and the RNA polymerase II gene were phylogenetically analyzed. That analysis resolved the 48 strains examined into five closely related species: K. telluris, Candida bovina, C. pintolopesii, Candida slooffiae, and a previously unknown species. One or more strains of each of the last four species formed an ascosporic state much like that of K. telluris. To place these ascosporogenous strains taxonomically, it is proposed that they be assigned to the teleomorphic genus Kazachstania as K. bovina (type strain NRRL Y-7283, CBS 9732, from the nasal passage of a pigeon), K. heterogenica (type strain NRRL Y-27499, CBS 2675, from rodent feces), K. pintolopesii (type strain NRRL Y-27500, CBS 2985, from the peritoneal fluid of a dead guinea pig), and K. slooffiae (type strain NRRL YB-4349, CBS 9733, from the cecum of a horse). On the basis of multigene sequence analyses, K. heterogenica appears to be a hybrid of K. pintolopesii and a presently unknown species. With the exception of K bovina, the phylogenetically defined species show a moderate degree of host specificity. C1 USDA ARS, Natl Ctr Agr Utilizat Res, Microbial Genomics & Bioproc Res Unit, Peoria, IL 61604 USA. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Baylor Coll Med, Ctr Comparat Med, Houston, TX 77030 USA. SAIC Frederick, Natl Canc Inst Frederick, Anim Hlth Diagnost Lab, Frederick, MD USA. RP Kurtzman, CP (reprint author), USDA ARS, Natl Ctr Agr Utilizat Res, Microbial Genomics & Bioproc Res Unit, 1815 N Univ St, Peoria, IL 61604 USA. EM kurtzman@ncaur.usda.gov FU NCI NIH HHS [N01-CO-56000] NR 25 TC 23 Z9 25 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 2005 VL 43 IS 1 BP 101 EP 111 DI 10.1128/JCM.43.1.101-111.2005 PG 11 WC Microbiology SC Microbiology GA 888NB UT WOS:000226380400013 PM 15634957 ER PT J AU Palmer, S Kearney, M Maldarelli, F Halvas, EK Bixby, CJ Bazmi, H Rock, D Falloon, J Davey, RT Dewar, RL Metcalf, JA Hammer, S Mellors, JW Coffin, JM AF Palmer, S Kearney, M Maldarelli, F Halvas, EK Bixby, CJ Bazmi, H Rock, D Falloon, J Davey, RT Dewar, RL Metcalf, JA Hammer, S Mellors, JW Coffin, JM TI Multiple, linked human immunodeficiency virus type 1 drug resistance mutations in treatment-experienced patients are missed by standard genotype analysis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID REVERSE-TRANSCRIPTASE; ANTIRETROVIRAL THERAPY; IN-VIVO; PROTEASE INHIBITORS; TREATMENT INTERRUPTION; MULTIDRUG-RESISTANCE; SEQUENCE ALIGNMENT; TREATMENT FAILURE; VIRAL RESISTANCE; HIV-1 AB To investigate the extent to which drug resistance mutations are missed by standard genotyping methods, we analyzed the same plasma samples from 26 patients with suspected multidrug-resistant human immunodeficiency virus type 1 by using a newly developed single-genome sequencing technique and compared it to standard genotype analysis. Plasma samples were obtained from patients with prior exposure to at least two antiretroviral drug classes and who were on a failing antiretroviral regimen. Standard genotypes were obtained by reverse transcriptase (RT)-PCR and sequencing of the bulk PCR product. For single-genome sequencing, cDNA derived from plasma RNA was serially diluted to 1 copy per reaction, and a region encompassing p6, protease, and a portion of RT was amplified and sequenced. Sequences from 15 to 46 single viral genomes were obtained from each plasma sample. Drug resistance mutations identified by single-genome sequencing were not detected by standard genotype analysis in 24 of the 26 patients studied. Mutations present in less than 10% of single genomes were almost never detected in standard genotypes (1 of 86). Similarly, mutations present in 10 to 35% of single genomes were detected only 25% of the time in standard genotypes. For example, in one patient, 10 mutations identified by single-genome sequencing and conferring resistance to protease inhibitors (PIs), nucleoside analog reverse transcriptase inhibitors, and nonnucleoside reverse transcriptase inhibitors (NNRTIs) were not detected by standard genotyping methods. Each of these mutations was present in 5 to 20% of the 20 genomes analyzed; 15% of the genomes in this sample contained linked PI mutations, none of which were present in the standard genotype. In another patient sample, 33% of genomes contained five linked NNRTI resistance mutations, none of which were detected by standard genotype analysis. These findings illustrate the inadequacy of the standard genotype for detecting low-frequency drug resistance mutations. In addition to having greater sensitivity, single-genome sequencing identifies linked mutations that confer high-level drug resistance. Such linkage cannot be detected by standard genotype analysis. C1 NCI, HIV Drig Resistance Program, NIH, Frederick, MD 21702 USA. SAIC Frederick, Frederick, MD 21702 USA. NIAID, Crit Care Med Dept Clin, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Columbia Univ, New York, NY USA. Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. RP Palmer, S (reprint author), NCI, HIV Drig Resistance Program, NIH, 1050 Boyles St,Bldg 535,Room 109, Frederick, MD 21702 USA. EM spalmer@ncifcrf.gov FU NIAID NIH HHS [U01 AI038858, U01AI38858] NR 48 TC 284 Z9 298 U1 1 U2 8 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 2005 VL 43 IS 1 BP 406 EP 413 DI 10.1128/JCM.43.1.406-413.2005 PG 8 WC Microbiology SC Microbiology GA 888NB UT WOS:000226380400058 PM 15635002 ER PT J AU Shepard, JW Buysse, DJ Chesson, AL Dement, WC Goldberg, R Guilleminault, C Harris, CD Iber, C Mignot, E Mitler, MM Moore, KE Phillips, BA Quan, SF Rosenberg, RS Roth, T Schmidt, HS Silber, MH Walsh, JK White, DP AF Shepard, John W., Jr. Buysse, Daniel J. Chesson, Andrew L., Jr. Dement, William C. Goldberg, Rochelle Guilleminault, Christian Harris, Cameron D. Iber, Conrad Mignot, Emmanuel Mitler, Merrill M. Moore, Kent E. Phillips, Barbara A. Quan, Stuart F. Rosenberg, Richard S. Roth, Thomas Schmidt, Helmut S. Silber, Michael H. Walsh, James K. White, David P. TI History of the Development of Sleep Medicine in the United States SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE Sleep medicine; history; sleep disorders; sleep research AB Sleep Medicine has only recently been recognized as a specialty of medicine. Its development is based on an increasing amount of knowledge concerning the physiology of sleep, circadian biology and the pathophysiology of sleep disorders. This review chronicles the major advances in sleep science over the past 70 years and the development of the primary organizations responsible for the emergence of Sleep Medicine as a specialty, sleep disorders as a public health concern and sleep science as an important area of research. C1 [Shepard, John W., Jr.; Harris, Cameron D.; Silber, Michael H.] Mayo Clin, Coll Med, Sleep Disorders Ctr, Rochester, MN USA. [Buysse, Daniel J.] Univ Pittsburgh, Sch Med, Dept Psychiat, Sleep & Chronobiol Program, Pittsburgh, PA USA. [Chesson, Andrew L., Jr.] Louisiana State Univ, Med Ctr, Dept Neurol, Shreveport, LA USA. [Dement, William C.; Guilleminault, Christian] Stanford Univ, Sleep Disorders Clin, Stanford, CA 94305 USA. [Dement, William C.] Stanford Univ, Res Ctr, Stanford, CA 94305 USA. [Dement, William C.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Goldberg, Rochelle] Sleep Med Serv, Wynnewood, PA USA. [Iber, Conrad] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Mignot, Emmanuel] Stanford Univ, Sch Med, Ctr Narcolepsy, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Mitler, Merrill M.] NINDS, Bethesda, MD 20892 USA. [Phillips, Barbara A.] Univ Kentucky, Med Ctr, Dept Med, Lexington, KY 40536 USA. [Quan, Stuart F.] Univ Arizona, Sleep Ctr, Tucson, AZ USA. [Quan, Stuart F.] Univ Arizona, Arizona Resp Ctr, Tucson, AZ USA. [Rosenberg, Richard S.] Amer Acad Sleep Med, Westchester, IL USA. [Roth, Thomas] Henry Ford Hosp, Dept Psychiat & Behav Neurosci, Sleep Disorders Ctr, Detroit, MI 48202 USA. [Schmidt, Helmut S.] Ohio Sleep Med & Neurosci Inst, Dublin, OH USA. [Silber, Michael H.] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN USA. [Walsh, James K.] St Lukes Hosp, Sleep Med & Res Ctr, Chesterfield, MO USA. [White, David P.] Brigham & Womens Hosp, Dept Med, Div Sleep Med, Boston, MA 02115 USA. RP Shepard, JW (reprint author), Mayo Clin & Mayo Grad Sch Med, Sleep Disorder Ctr, 200 First St Southwest, Rochester, MN 55905 USA. EM shepard.john2@mayo.edu FU Sanofi; Cephalon; Pfizer; Somaxon; Syrex; Takeda; Neurocrine; GlaxoSmithKline; Aventis; Sepracor; Respironics; Itamar Medical; Alfred E. Mann Foundation; WideMed FX This was not an industry supported study. Dr. Buysse has a consulting relationship with Actelion, Cephalon, Eli Lilly, Merck, Neurocrine, Pfizer, Respironics, Sanofi-Synthelabo, Sepracor, and Takeda; and has participated in speaking engagements supported by Neurocrine, Pfizer, Sanofi-Synthelabo, and Sepracor. Dr. Iber is on the academic advisory board of the AASM/Pfizer visiting professorships in Sleep Medicine. Dr. Quan is a member of the 2005 Pfizer Academic Scholar Board. Dr. Roth has received research support from Sanofi, Cephalon, Pfizer, Somaxon, Syrex, Takeda, Neurocrine, GlaxoSmithKline, Aventis, and Sepracor; is a consultant for Transoral, Sanofi, Cephalon, Merck, Pfizer, Somaxon, Vivometrics, Syrex, Takeda, Neurocrine, GlaxoSmithKline, Eli Lilly, Wyeth, Aventis, Sepracor, Roche, Organaon, AstraZenca, McNeil, Lundbeck, Hypnion, Orginer, and King; and has participated in speaking engagements supported by Sanofi. Dr. White has received research support from Respironics, Itamar Medical, Alfred E. Mann Foundation, and WideMed; and has a consulting relationship with Respironics, Itamar Medical, Alfred E. Mann Foundation, Aspire Medical, and WideMed. Drs. Chesson, Dement, Goldberg, Guilleminault, Harris, Mignot, Mitler, Moore, Phillips, Rosenberg, Schmidt, Shepard, Silber, and Walsh have indicated no financial conflicts of interest. NR 158 TC 37 Z9 38 U1 3 U2 5 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2005 VL 1 IS 1 BP 61 EP 82 PG 22 WC Clinical Neurology SC Neurosciences & Neurology GA V44UZ UT WOS:000209775200013 PM 17561617 ER PT J AU Dolan-Sewell, RT Riley, WT Hunt, CE AF Dolan-Sewell, Regina T. Riley, William T. Hunt, Carl E. TI NIH State-of-the-Science Conference on Chronic Insomnia SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Editorial Material C1 [Dolan-Sewell, Regina T.; Riley, William T.] NIMH, Bethesda, MD 20892 USA. [Hunt, Carl E.] NHLBI, Natl Ctr Sleep Disorders Res, Bethesda, MD 20892 USA. RP Dolan-Sewell, RT (reprint author), NIMH, Bethesda, MD 20892 USA. NR 1 TC 4 Z9 4 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2005 VL 1 IS 4 BP 335 EP 336 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA V44VC UT WOS:000209775500026 PM 17564396 ER PT J AU Carver, F Feeney, M Mitchell-Francis, J Holroyd, T Coppola, R AF Carver, F Feeney, M Mitchell-Francis, J Holroyd, T Coppola, R TI Multiple sources of the auditory oddball response revealed by synthetic aperture magnetometry SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 12th Annnual Meeting of the Cognitive-Neuroscience-Society CY APR 09-12, 2005 CL New York, NY SP Cognit Neurosci Soc C1 NIMH, MEG Core Facil, Bethesda, MD USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2005 SU S BP 18 EP 18 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 909RP UT WOS:000227878700042 ER PT J AU Lee, L Friston, KJ Horwitz, B AF Lee, L Friston, KJ Horwitz, B TI Large-scale neural models and dynamic causal modelling: A cross validation. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 12th Annual Meeting of the Cognitive-Neuroscience-Society CY APR 09-12, 2005 CL New York, NY SP Cognit Neurosci Soc C1 UCL, Wellcome Dept Imaging Neurosci, London, England. NIDOCD, Brain Imaging & Modeling Sect, NIH, Bethesda, MD USA. RI Friston, Karl/D-9230-2011 OI Friston, Karl/0000-0001-7984-8909 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X EI 1530-8898 J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2005 SU S BP 32 EP 32 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 909RP UT WOS:000227878700109 ER PT J AU Alia-Klein, N Goldstein, RZ Tomasi, D Cottone, L Fowler, J Wang, GJ Volkow, ND AF Alia-Klein, N Goldstein, RZ Tomasi, D Cottone, L Fowler, J Wang, GJ Volkow, ND TI Role of genotype in cingulate function and inhibitory control: A functional magnetic resonance imaging (FMRI) study SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 12th Annnual Meeting of the Cognitive-Neuroscience-Society CY APR 09-12, 2005 CL New York, NY SP Cognit Neurosci Soc C1 NIDA, Med Dept, Brookhaven Natl Lab, NIH, Bethesda, MD USA. RI Tomasi, Dardo/J-2127-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2005 SU S BP 33 EP 34 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 909RP UT WOS:000227878700116 ER PT J AU Finger, E Snow, J Fridberg, D Budhani, S Mondillo, K Vythilingam, M Bonne, O Blair, J AF Finger, E Snow, J Fridberg, D Budhani, S Mondillo, K Vythilingam, M Bonne, O Blair, J TI Impaired passive avoidance learning in PTSD patients SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 12th Annnual Meeting of the Cognitive-Neuroscience-Society CY APR 09-12, 2005 CL New York, NY SP Cognit Neurosci Soc C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2005 SU S BP 65 EP 65 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 909RP UT WOS:000227878700260 ER PT J AU Roiser, J Blackwell, A Cools, R Clark, L Robbins, T Sahakian, B AF Roiser, J Blackwell, A Cools, R Clark, L Robbins, T Sahakian, B TI Serotonin transporter polymorphism mediates vulnerability to loss of motivated action following acute tryptophan depletion SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 12th Annnual Meeting of the Cognitive-Neuroscience-Society CY APR 09-12, 2005 CL New York, NY SP Cognit Neurosci Soc C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA. Univ Cambridge, Dept Psychiat, Cambridge CB2 1TN, England. Univ Cambridge, Dept Expt Psychol, Cambridge CB2 1TN, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2005 SU S BP 65 EP 65 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 909RP UT WOS:000227878700257 ER PT J AU Breitenstein, C Kamping, S Gieseking, I Korsukewitz, C Drager, B Floel, A Knecht, S AF Breitenstein, C Kamping, S Gieseking, I Korsukewitz, C Drager, B Floel, A Knecht, S TI Wernicke's area and language acquisition: A transcranial magnetic stimulation study SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 12th Annnual Meeting of the Cognitive-Neuroscience-Society CY APR 09-12, 2005 CL New York, NY SP Cognit Neurosci Soc C1 Univ Munster, D-4400 Munster, Germany. NINDS, NIH, Bethesda, MD USA. RI Floel, Agnes/A-9426-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2005 SU S BP 71 EP 71 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 909RP UT WOS:000227878700287 ER PT J AU Knecht, S Rogalewski, A Jansen, A Floel, A Foerster, AF Deppe, M Breitenstein, C AF Knecht, S Rogalewski, A Jansen, A Floel, A Foerster, AF Deppe, M Breitenstein, C TI Transmodal activation of the mirror neuron system: Listening to speech prosody activates the cortical motor representation of the right hand SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 12th Annnual Meeting of the Cognitive-Neuroscience-Society CY APR 09-12, 2005 CL New York, NY SP Cognit Neurosci Soc C1 Univ Munster, Dept Neurol, D-4400 Munster, Germany. Univ Munster, IZKF Muenster, D-4400 Munster, Germany. NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. Ruhr Univ Bochum, BG Kliniken Bergmannsheil, Dept Radiol, D-4630 Bochum, Germany. RI Floel, Agnes/A-9426-2017; Deppe, Michael/C-5780-2017 OI Deppe, Michael/0000-0002-8372-9678 NR 0 TC 0 Z9 0 U1 0 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2005 SU S BP 92 EP 92 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 909RP UT WOS:000227878700384 ER PT J AU Floel, A Garraux, G Giraux, P Schaefer, M Breitenstein, C Herscovitch, P Knecht, S Cohen, LG AF Floel, A Garraux, G Giraux, P Schaefer, M Breitenstein, C Herscovitch, P Knecht, S Cohen, LG TI Dopaminergic influences on motor memory formation in the elderly. A combined behavioral-TMS/PET study. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 12th Annnual Meeting of the Cognitive-Neuroscience-Society CY APR 09-12, 2005 CL New York, NY SP Cognit Neurosci Soc C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Univ Munster, Dept Neurol, D-4400 Munster, Germany. Univ Munster, IZKF Munster, D-4400 Munster, Germany. NIH, Ctr Clin, Positron Emiss Tomog Imaging Sect, Bethesda, MD 20892 USA. RI Garraux, Gaetan/G-9050-2011; Floel, Agnes/A-9426-2017 NR 0 TC 0 Z9 0 U1 0 U2 2 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2005 SU S BP 104 EP 104 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 909RP UT WOS:000227878700439 ER PT J AU Barense, M Bussey, T Lee, A Rogers, T Hodges, J Saksida, L Murray, E Kim, G AF Barense, M Bussey, T Lee, A Rogers, T Hodges, J Saksida, L Murray, E Kim, G TI Feature ambiguity influences performance on novel object discriminations in patients with damage to perirhinal cortex SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 12th Annnual Meeting of the Cognitive-Neuroscience-Society CY APR 09-12, 2005 CL New York, NY SP Cognit Neurosci Soc C1 MRC, Cognit & Brain Sci Unit, Cambridge, England. Univ Cambridge, Dept Expt Psychol, Cambridge CB2 1TN, England. NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2005 SU S BP 129 EP 129 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 909RP UT WOS:000227878700555 ER PT J AU Yang, JJ Francis, N Bellgowan, PSF Martin, A AF Yang, JJ Francis, N Bellgowan, PSF Martin, A TI Object concepts and the human amygdala: Enhanced activity for identifying animals independent of in-put modality and stimulus format SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 12th Annnual Meeting of the Cognitive-Neuroscience-Society CY APR 09-12, 2005 CL New York, NY SP Cognit Neurosci Soc C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RI martin, alex/B-6176-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2005 SU S BP 176 EP 176 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 909RP UT WOS:000227878701138 ER PT J AU Hwang, GC Eapen, M Japee, S Hendler, T Ungerleider, L AF Hwang, GC Eapen, M Japee, S Hendler, T Ungerleider, L TI Emotional modulation of selection into awareness of face percepts: An fMRI study SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 12th Annnual Meeting of the Cognitive-Neuroscience-Society CY APR 09-12, 2005 CL New York, NY SP Cognit Neurosci Soc C1 NIMH, NIH, Lab Brain & Cognit, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2005 SU S BP 196 EP 196 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 909RP UT WOS:000227878701229 ER PT J AU Eldreth, D Fishbein, D Hyde, C Matochik, J Grant, S London, E AF Eldreth, D Fishbein, D Hyde, C Matochik, J Grant, S London, E TI Neural substrates of emotional perception deficits in abstinent drug abusers SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 12th Annnual Meeting of the Cognitive-Neuroscience-Society CY APR 09-12, 2005 CL New York, NY SP Cognit Neurosci Soc C1 NIDA, Div Clin Neurobiol, Lexington, KY 40583 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2005 SU S BP 200 EP 200 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 909RP UT WOS:000227878701247 ER PT J AU Vaidya, C Kaplan, L Kenworthy, L Gilotty, L Girton, L Fos, J Lacey, E Gaillard, W AF Vaidya, C Kaplan, L Kenworthy, L Gilotty, L Girton, L Fos, J Lacey, E Gaillard, W TI Altered neural basis of controlling interference from social and non-social information in childhood autism: A functional magnetic resonance study SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 12th Annnual Meeting of the Cognitive-Neuroscience-Society CY APR 09-12, 2005 CL New York, NY SP Cognit Neurosci Soc C1 Georgetown Univ, Washington, DC 20057 USA. Columbia Univ, New York, NY 10027 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2005 SU S BP 222 EP 222 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 909RP UT WOS:000227878701344 ER PT J AU Delosh, D Leskovjan, AC Cottone, LA Alia-Klein, N Wong, GJ Fowler, JS Volkow, ND Goldstein, RZ AF Delosh, D Leskovjan, AC Cottone, LA Alia-Klein, N Wong, GJ Fowler, JS Volkow, ND Goldstein, RZ TI Cocaine addiction is associated with impaired learning on the Wisconsin Card Sort Task: Findings in high functioning individuals SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 12th Annnual Meeting of the Cognitive-Neuroscience-Society CY APR 09-12, 2005 CL New York, NY SP Cognit Neurosci Soc C1 Brookhaven Natl Lab, Upton, NY 11973 USA. NIDA, NIH, Lexington, KY 40583 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2005 SU S BP 226 EP 226 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 909RP UT WOS:000227878701363 ER PT J AU van Raalten, T Jansma, M Ramsey, N Duyn, J AF van Raalten, T Jansma, M Ramsey, N Duyn, J TI An FMRI study of practice-effects on separate processes of a Sternberg task SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 12th Annnual Meeting of the Cognitive-Neuroscience-Society CY APR 09-12, 2005 CL New York, NY SP Cognit Neurosci Soc C1 UMC Utrecht, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands. NINDS, LFMI, NIH, Bethesda, MD 20892 USA. RI Duyn, Jozef/F-2483-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2005 SU S BP 244 EP 244 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 909RP UT WOS:000227878701444 ER PT J AU Jansma, M van Gelderen, P van Raalten, T Ramsey, N Duyn, J AF Jansma, M van Gelderen, P van Raalten, T Ramsey, N Duyn, J TI High resolution spatial separation of functional processes in a Sternberg task using FMRI. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 12th Annnual Meeting of the Cognitive-Neuroscience-Society CY APR 09-12, 2005 CL New York, NY SP Cognit Neurosci Soc C1 NINDS, LFMI, Adv MRI Sect, NIH, Bethesda, MD USA. Univ Utrecht, Med Ctr, Funct Imaging Sect, Utrecht, Netherlands. RI Duyn, Jozef/F-2483-2010 NR 0 TC 0 Z9 0 U1 1 U2 2 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2005 SU S BP 245 EP 245 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 909RP UT WOS:000227878701448 ER PT J AU Green, SL Westendorf, JM Jaffe, H Pant, HC Cork, LC Ostrander, EA Vignaux, F Ferrell, JE AF Green, SL Westendorf, JM Jaffe, H Pant, HC Cork, LC Ostrander, EA Vignaux, F Ferrell, JE TI Allelic variants of the canine heavy neurofilament (NFH) subunit and extensive phosphorylation in dogs with motor neuron disease SO JOURNAL OF COMPARATIVE PATHOLOGY LA English DT Article DE dog; motor neuron disease; neurofilament protein; phosphorylation ID SPINAL MUSCULAR-ATROPHY; AMYOTROPHIC-LATERAL-SCLEROSIS; RADIATION HYBRID MAP; SUPEROXIDE-DISMUTASE; PROTEIN INVITRO; GENOME; GENE; IDENTIFICATION; CONSTRUCTION; ARCHITECTURE AB Aberrant accumulation of extensively phosphorylated heavy (high molecular weight) neurofilament (NFH) and neurodegeneration are features of hereditary canine spinal muscular atrophy (HCSMA), an animal model of human motor neuron disease. In this study, the canine NFH gene was mapped, cloned, and sequenced, and electrospray/mass spectrometry was used to evaluate the phosphorylation state of NFH protein from normal dogs and dogs with HCSMA. The canine NFH gene was localized to a region on canine chromosome 26 that corresponds to human NFH on chromosome 22q. The predicted length of the canine NFH protein is 1135 amino acids, and it shares an 80.3% identity with human NFH and >74.6% with murine NFH proteins. Direct sequencing of NFH cDNA from HCSMA dogs revealed no mutations, although cDNA sequence and restriction fragment length polymorphism (RFLP) analysis indicates that there are at least three canine NFH alleles, differing in the position and number (61 or 62) of Lys-Ser-Proline (KSP) motifs. The two longest alleles (L1 and L2), each with 62 KSP repeats, contain an additional 24-base insert and were observed in both normal and HCSMA dogs. However, the shorter allele (the C allele), with 61 KSP sites and lacking the 24-base insertion, was absent in dogs with HCSMA. Mass spectrometry data indicated that almost all of the NFH KSP phosphorylation sites were occupied. No new or extra sites were identified in native NFH purified from the HCSMA dogs. The predominance of the two longest NFH alleles and the additional KSP phosphorylation sites they confer probably account for the presence of extensively phosphorylated NFs detected immunohistochemically in dogs with HCSMA. (C) 2004 Elsevier Ltd. All rights reserved. C1 Stanford Univ, Dept Comparat Med, Stanford, CA 94305 USA. Stanford Univ, Dept Mol Pharmacol, Stanford, CA 94305 USA. NINDS, Prot Peptide Sequencing Facil & Lab Neurochem, NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res & Human Biol, Seattle, WA 98109 USA. Fac Med, F-35043 Rennes, France. RP Green, SL (reprint author), Stanford Univ, Dept Comparat Med, RAF 1,Quad 7,Bldg 330, Stanford, CA 94305 USA. OI Ostrander, Elaine/0000-0001-6075-9738 FU NCRR NIH HHS [RR00132-04]; NIGMS NIH HHS [GM46383]; NINDS NIH HHS [NS31621] NR 39 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0021-9975 J9 J COMP PATHOL JI J. Comp. Pathol. PD JAN PY 2005 VL 132 IS 1 BP 33 EP 50 DI 10.1016/j.jcpa.2004.06.003 PG 18 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 890TW UT WOS:000226534700003 PM 15629478 ER PT J AU Gong, SG Gong, TW Shum, L AF Gong, SG Gong, TW Shum, L TI Identification of markers of the midface SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE primary palate; microarray analysis; RT-qPCR ID PROGRAMMED CELL-DEATH; HEAD INDUCTION; GENE; DICKKOPF-1; EXPRESSION; FGF; REGION; FAMILY; BMP AB Currently, much remains unknown of the genes that mediate the biological events during growth and fusion of the midfacial region, and the possible pathways through which these genes function. We took advantage of high-throughput microarray analysis to search for genes that may play a critical role in the growth and fusion of the midfacial region to become the primary palate. We identified several genes that were potentially expressed at different levels between tail somite (TS) 6-8 (pre-fusion) and TS 12-14 (fusion) in the 3 midfacial processes. Expression of 4 of these genes (Tbx14/15, Dickkopf-1, Fibroblast Growth Factor 8, and Keratin-18) was further verified by reverse-transcription/quantitative PCR and in situ hybridization at the 2 stages of midfacial development. With the identification of these genes, and possibly others, functional analyses can be conducted to improve our understanding of the mechanisms and pathways by which the midface forms. C1 Univ Michigan, Sch Dent, Dept Orthodont & Pediat Dent, Ann Arbor, MI 48109 USA. Univ Michigan, Kresge Hearing Res Inst, Dept Otolaryngol Head Neck Surg, Ann Arbor, MI 48109 USA. NICDCR, Physiol Pharmacogenet & Injury Program, Div Basic & Translat Sci, NIH, Bethesda, MD 20892 USA. RP Gong, SG (reprint author), Univ Michigan, Sch Dent, Dept Orthodont & Pediat Dent, 1011 N Univ Ave, Ann Arbor, MI 48109 USA. EM sggong@umich.edu NR 14 TC 14 Z9 14 U1 0 U2 0 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 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JAN PY 2005 VL 84 IS 1 BP 69 EP 72 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 895AV UT WOS:000226834000012 PM 15615879 ER PT J AU Hearing, VJ AF Hearing, VJ TI Biogenesis of pigment granules: a sensitive way to regulate melanocyte function SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Review ID OCULOCUTANEOUS ALBINISM TYPE-1; HERMANSKY-PUDLAK-SYNDROME; DHICA OXIDASE ACTIVITY; MELANOSOME BIOGENESIS; ENDOPLASMIC-RETICULUM; GRISCELLI-SYNDROME; MELANOCORTIN-1 RECEPTOR; HUMAN TYROSINASE; PROTEINS; MODEL AB Pigmentation not only provides a wide range of cosmetic coloration to the skin, hair and eyes, but also provides the underlying tissue significant protection from ultraviolet (UV) damage, which can lead to photoaging and photocarcinogenesis. The melanin pigment is synthesized and deposited within a unique, membrane-bound organelle termed the melanosome. Recent advances in molecular biology and biochemistry have allowed a greater appreciation of how melanocytes generate this organelle and how its biogenesis, structure and function is regulated by the environment. Melanosomes serve as ideal models for the study of organelle biogenesis.. protein trafficking, organelle movement and cell-cell interactions that occur during the transfer of melanosomes to keratinocytes. Our understanding of the mechanisms behind a wide range of human pigmentary diseases have grown remarkably as melanosomes have been unraveled. Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology. C1 NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hearing, VJ (reprint author), NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bldg 37,Room 2132, Bethesda, MD 20892 USA. EM hearingv@nih.gov NR 57 TC 154 Z9 166 U1 2 U2 16 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD JAN PY 2005 VL 37 IS 1 BP 3 EP 14 DI 10.1016/j.jdermsci.2004.08.014 PG 12 WC Dermatology SC Dermatology GA 892FR UT WOS:000226636000001 PM 15619429 ER PT J AU Nagorsen, D Fetsch, PA Abati, A Marincola, FM Panelli, MC AF Nagorsen, D Fetsch, PA Abati, A Marincola, FM Panelli, MC TI Degree of CD14 expression in melanoma infiltrating mononuclear phagocytes SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Letter ID DENDRITIC CELLS; MONOCYTES; MACROPHAGES; RECEPTORS C1 NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Univ Med Berlin, Charite, Berlin, Germany. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Panelli, MC (reprint author), NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM mpanelli@cc.nih.gov NR 10 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD JAN PY 2005 VL 37 IS 1 BP 52 EP 54 DI 10.1016/j.jdermsci.2004.09.007 PG 3 WC Dermatology SC Dermatology GA 892FR UT WOS:000226636000007 PM 15619435 ER PT J AU Knowler, WC Coresh, J Elston, RC Freedman, BI Iyengar, SK Kimmel, PL Olson, JM Plaetke, R Sedor, JR Seldin, MF AF Knowler, WC Coresh, J Elston, RC Freedman, BI Iyengar, SK Kimmel, PL Olson, JM Plaetke, R Sedor, JR Seldin, MF TI The Family Investigation of Nephropathy and Diabetes (FIND) Design and methods SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE nephropathy; diabetes; genetics; linkage; admixture ID STAGE RENAL-DISEASE; ADMIXTURE LINKAGE DISEQUILIBRIUM; AFRICAN-AMERICANS; PIMA-INDIANS; INSERTION/DELETION POLYMORPHISM; MEXICAN-AMERICANS; HUMAN-POPULATIONS; TYPE-2 DIABETES/; NITRIC-OXIDE; RISK-FACTORS AB Background: The Family Investigation of Nephropathy and Diabetes (FIND) is a multicenter study designed to identify genetic determinants of diabetic nephropathy. It is conducted in eight U.S. clinical centers and a coordinating center, and with four ethnic groups (European Americans, African Americans, Mexican Americans, and American Indians). Two strategies are used to localize susceptibility genes: a family-based linkage study and a case-control study using mapping by admixture linkage disequilibrium (MALD). Methods: In the family-based study, probands with diabetic nephropathy are recruited with their parents and selected siblings. Linkage analyses will be conducted to identify chromosomal regions containing genes that influence the development of diabetic nephropathy or related quantitative traits such as serum creatinine concentration, urinary albumin excretion, and plasma glucose concentrations. Regions showing evidence of linkage will be examined further with both genetic linkage and association studies to identify genes that influence diabetic nephropathy or related traits. Two types of MALD studies are being done. One is a case-control study of unrelated individuals of Mexican American heritage in which both cases and controls have diabetes, but only the case has nephropathy. The other is a case-control study of African American patients with nephropathy (cases) and their spouses (controls) unaffected by diabetes and nephropathy; offspring are genotyped when available to provide haplotype data. Conclusions: Identification of genes that influence susceptibility to diabetic nephropathy will lead to a better understanding of how nephropathy develops. This should eventually lead to improved treatment and prevention. (C) 2005 Elsevier Inc. All rights reserved. C1 Case Western Reserve Univ, Metrohlth Med Ctr, Dept Genet Epidemiol & Biostat, Cleveland, OH 44109 USA. NIDDKD, Diabet & Arthrit Epidemiol Sect, Phoenix, AZ USA. Johns Hopkins Univ, Dept Epidemiol Biostat & Med, Baltimore, MD 21218 USA. Wake Forest Univ, Dept Internal Med Nephrol, Winston Salem, NC 27109 USA. NIDDKD, Diabet Nephropathy Program, Bethesda, MD 20892 USA. NIDDKD, HIV Program, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78285 USA. Case Western Reserve Univ, Kammelkamp Ctr Res & Educ, Cleveland, OH 44109 USA. Univ Calif Davis, Dept Biol Chem & Med, Davis, CA 95616 USA. RP Elston, RC (reprint author), Case Western Reserve Univ, Metrohlth Med Ctr, Dept Genet Epidemiol & Biostat, 2500 MetroHlth Dr,Rammelkamp 258, Cleveland, OH 44109 USA. RI Nelson, Robert/B-1470-2012; OI Jun, Gyungah/0000-0002-3230-8697 NR 57 TC 62 Z9 64 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD JAN-FEB PY 2005 VL 19 IS 1 BP 1 EP 9 DI 10.1016/j.jdiacomp.2003.12.007 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 896VF UT WOS:000226961400001 PM 15642484 ER PT J AU Buenz, EJ Johnson, HE Beekman, EM Motley, TJ Bauer, BA AF Buenz, EJ Johnson, HE Beekman, EM Motley, TJ Bauer, BA TI Bioprospecting Rumphius's Ambonese herbal: Volume I SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Review DE historic text; ambon; Rumphius; Indonesia; Ethnobotany; medicinal; plants ID PLANT-PATHOGENIC FUNGI; MEDICINAL-PLANTS; GARCINIA-MANGOSTANA; ANTIMICROBIAL ACTIVITY; BETA-SITOSTEROL; PROSTAGLANDIN BIOSYNTHESIS; 2-STAGE CARCINOGENESIS; VOLATILE COMPOUNDS; FLAVOR COMPOUNDS; TUMOR PROMOTION AB Collaborating with traditional healers remains a valid method for the identification of potential lead compounds for novel pharmaceuticals. However, the knowledge of these traditional healers is rapidly being lost. Historic herbal texts provide a unique window to identify plants whose specific uses are no longer known. We have identified nine plants in the 17th century Ambonese Herbal: Volume 1 which were documented as having medicinal properties but which have not been examined in the current literature. We demonstrate that by evaluating plant and herb efficacy reports from historic texts, in the context of comprehensive modern databases such as NAPRALERT(TM), we can ultimately identify candidate specimens deserving further pharmacological study. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Mayo Clin & Mayo Fdn, Mayo Coll Med, Complementary & Integrat Med Program, Rochester, MN 55905 USA. Univ Illinois, NIH, Ctr Bot Dietary Supplements Res, Chicago, IL USA. Univ Massachusetts, Amherst, MA 01003 USA. New York Bot Garden, Lewis B & Dorothy Cullman Program Mol Systemat St, Bronx, NY 10458 USA. RP Buenz, EJ (reprint author), Mayo Clin & Mayo Fdn, Mayo Coll Med, Complementary & Integrat Med Program, 200 1st St NW, Rochester, MN 55905 USA. EM buenz.eric@mayo.edu OI , Eric/0000-0002-4053-7422 NR 139 TC 23 Z9 25 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-8741 J9 J ETHNOPHARMACOL JI J. Ethnopharmacol. PD JAN PY 2005 VL 96 IS 1-2 BP 57 EP 70 DI 10.1016/j.jep.2004.08.016 PG 14 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 881LS UT WOS:000225869600007 PM 15588651 ER PT J AU De Joode, BV Tielemans, E Vermeulen, R Wegh, H Kromhout, H AF De Joode, BV Tielemans, E Vermeulen, R Wegh, H Kromhout, H TI Dermal exposure assessment to benzene and toluene using charcoal cloth pads SO JOURNAL OF EXPOSURE ANALYSIS AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE dermal exposure; charcoal cloth pads; benzene; toluene ID S-PHENYLMERCAPTURIC ACID AB Charcoal cloth pads have been used to assess volatile chemicals on the skin in a laboratory setting; however, they have not yet been applied to measure dermal exposure in occupational settings. This study aimed at evaluating whether charcoal pads can be used to assess dermal exposure to benzene and toluene in workers of a petrochemical plant. Inhalation and dermal exposure levels to benzene and toluene were assessed for workers of a petrochemical plant performing different jobs. Benzene uptake was assessed by determining S-phenylmercapturic acid in workers' urine samples. Dermal exposure levels on the charcoal pads were adjusted for ambient air levels of benzene and toluene by subtracting the amount of benzene or toluene measured in personal air from the amount of benzene or toluene measured on the charcoal pad. In general, measured external and internal exposure levels were low. The estimated contribution of the dermal route to internal benzene exposure levels was less than 0.06% for all jobs. Toluene personal air concentrations and benzene and toluene dermal exposure levels differed statistically significantly between job titles. For benzene, differences between jobs were larger for adjusted dermal exposures ( maximum 17-fold, P = 0.02) than for inhalation exposures ( maximum two-fold, P = 0.08). Also for toluene, although less clear, differences between jobs were larger for adjusted dermal exposures ( maximum 23-fold, P = 0.01) as compared to inhalation exposures ( maximum 10-fold, P = 0.01). Charcoal pads appeared to measure dermal exposures to benzene and toluene in addition to ambient air levels. Future studies applying charcoal cloth pads for the dermal exposure assessment at workplaces with higher dermal exposure to organic solvents may provide more insight into the biological relevance of dermal exposure levels measured by charcoal cloth pads. In addition, the design of the dermal sampler might be improved by configuring a dermal sampler, where part of the sampler is protected against direct contact and splashes, but still permeable for the gas phase. This design would most likely result in a better ability to correct for airborne concentrations at a given body location. C1 Univ Utrecht, Inst Risk Assessment Sci, Environm & Occupat Hlth Div, NL-3508 TD Utrecht, Netherlands. TNO Chem, Dept Chem Exposure Assessment, Zeist, Netherlands. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. Univ Wageningen & Res Ctr, Wageningen, Netherlands. RP De Joode, BV (reprint author), Univ Utrecht, Inst Risk Assessment Sci, Environm & Occupat Hlth Div, POB 80176, NL-3508 TD Utrecht, Netherlands. EM b.vanwendel@iras.uu.nl RI Kromhout, Hans/A-9159-2008; Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 NR 7 TC 7 Z9 7 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1053-4245 J9 J EXPO ANAL ENV EPID JI J. Expo. Anal. Environ. Epidemiol. PD JAN PY 2005 VL 15 IS 1 BP 47 EP 50 DI 10.1038/sj.jea.7500349 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 884ZO UT WOS:000226125400006 ER PT J AU Stager, SV Calis, K Grothe, D Bloch, M Berensen, NM Smith, PJ Braun, A AF Stager, SV Calis, K Grothe, D Bloch, M Berensen, NM Smith, PJ Braun, A TI Treatment with medications affecting dopaminergic and serotonergic mechanisms: Effects on fluency and anxiety in persons who stutter SO JOURNAL OF FLUENCY DISORDERS LA English DT Article DE stuttering; dopaminergic; serotonergic; anxiety; fluency ID OBSESSIVE-COMPULSIVE DISORDER; POSITRON-EMISSION-TOMOGRAPHY; CLOMIPRAMINE TREATMENT; CONTROLLED TRIAL; HALOPERIDOL; SPEECH; DESIPRAMINE; PAROXETINE; NONSTUTTERERS; MEPROBAMATE AB Medications with dopamine antagonist properties, such as haloperidol, and those with serotonin reuptake inhibitor properties, such as clomipramine, have been shown to improve fluency. To examine the degree to which each of these two pharmacological mechanisms might independently affect fluency, a selective serotonin reuptake inhibitor, paroxetine, and a selective dopamine (D-2) antagonist, pimozide, were evaluated. Both types of medications also affect mood and anxiety, factors that could influence fluency levels. Therefore, we also evaluated the medications' effects on generalized and speech-related anxiety and the relationships between changes in anxiety and changes in fluency in 11 subjects with a history of developmental stuttering. The randomized, double blind, placebo-controlled crossover study that was designed had to be terminated prior to completion due to severe side effects following withdrawal from paroxetine. Even with a reduced sample size (n=6), significant improvement in percent fluent speaking time (p=0.02) was found using a telephone task between baseline and pimozide (n=6), with average duration of dysfluencies significantly shorter (p=0.04) but no significant difference in the estimated number of dysfluencies per minute. This significant improvement was associated with non-significant increases in generalized anxiety, but non-significant decreases in speech-related anxiety. No significant differences were found in fluency between baseline and paroxetine (n=5). These preliminary results suggest that fluency improvement is more likely to be mediated by dopaminergic rather than serotonergic mechanisms. Due to its side effects, however, pimozide may be considered a risk for treatment of stuttering. Educational objectives: As a result of reading this paper the reader will describe and explain: (1) how medications may affect fluency and the rationale for selecting medications for treatment trials; (2) the interrelationship between fluency and anxiety; and (3) factors important in developing clinical trials using medications. (c) 2005 Elsevier Inc. All rights reserved. C1 NIDCD, Voice & Speech Sect, Bethesda, MD 20892 USA. Magnuson Clin Ctr, Dept Pharm, Bethesda, MD 20892 USA. NIMH, Behav Psychiat Branch, Bethesda, MD 20892 USA. Univ Maryland, Dept Math, Stat Program, College Pk, MD 20742 USA. NIDCD, Language Sect, Bethesda, MD 20892 USA. RP Stager, SV (reprint author), George Washington Univ, Med Fac Associates Voice Treatment Ctr, 2150 Penn Ave NW,Suite 6-301, Washington, DC 20037 USA. EM sstager@mfa.gwu.edu OI Stager, Sheila/0000-0002-4294-2114 NR 60 TC 20 Z9 21 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0094-730X J9 J FLUENCY DISORD JI J. Fluency Disord. PY 2005 VL 30 IS 4 BP 319 EP 335 DI 10.1016/j.jfludis.2005.09.004 PG 17 WC Audiology & Speech-Language Pathology; Education, Special; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Education & Educational Research; Linguistics; Rehabilitation GA 996KG UT WOS:000234172200003 PM 16246409 ER PT J AU Moore, BA Augustson, EM Moser, RP Budney, AJ AF Moore, BA Augustson, EM Moser, RP Budney, AJ TI Respiratory effects of marijuana and tobacco use in a U.S. Sample SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Annual Scientific Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 12-17, 2003 CL Bal Harbour, FL SP Coll Problems Drug Dependence DE marijuana; tobacco; smoking; respiratory symptoms; epidemiology ID SMOKING MARIJUANA; HABITUAL SMOKERS; AND/OR TOBACCO; HEAVY SMOKERS; COCAINE; CIGARETTES; DEPOSITION; LUNG; TAR AB OBJECTIVE: Although a number of studies have examined the respiratory impact of marijuana smoking, such studies have generally used convenience samples of marijuana and tobacco users. The current study examined respiratory effects of marijuana and tobacco use in a nationally representative sample while controlling for age, gender, and current asthma. DESIGN: Analysis of the nationally representative third National Health and Nutrition Examination Survey (NHANES III). SETTING: U.S. households. PARTICIPANTS: A total of 6,728 adults age 20 to 59 who completed the drug, tobacco, and health sections of the NHANES III questionnaire in 1988 and 1994. Current marijuana use was defined as self-reported 100+ lifetime use and at least 1 day of use in the past month. MEASUREMENTS AND MAIN RESULTS: Self-reported respiratory symptoms included chronic bronchitis, frequent phlegm, shortness of breath, frequent wheezing, chest sounds without a cold, and pneumonia. A medical exam also provided an overall chest finding and a measure of reduced pulmonary functioning. Marijuana use was associated with respiratory symptoms of chronic bronchitis (P=.02), coughing on most days (P=.001), phlegm production (P=.0005), wheezing (P<.0001), and chest sounds without a cold (P=.02). CONCLUSION: The impact of marijuana smoking on respiratory health has some significant similarities to that of tobacco smoking. Efforts to prevent and reduce marijuana use, such as advising patients to quit and providing referrals for support and assistance, may have substantial public health benefits associated with decreased respiratory health problems. C1 Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06519 USA. NCI, Tobacco Control Res Branch, Div Canc Control & Populat Sci, Rockville, MD USA. NCI, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD USA. Univ Vermont, Dept Psychol, Burlington, VT 05405 USA. Univ Vermont, Dept Psychiat, Burlington, VT 05405 USA. RP Moore, BA (reprint author), Yale Univ, Sch Med, Dept Psychiat, 219S CMHC-SAC,34 Pk St, New Haven, CT 06519 USA. EM Brent.Moore@Yale.edu RI Moore, Brent/O-4867-2015 OI Moore, Brent/0000-0003-0123-6616 FU NIDA NIH HHS [R01-DA12157, T32 DA007242, T32-DA07242] NR 27 TC 59 Z9 59 U1 1 U2 12 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2005 VL 20 IS 1 BP 33 EP 37 DI 10.1111/j.1525-1497.2004.40081.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 895YF UT WOS:000226899900006 PM 15693925 ER PT J AU Davison, AJ Trus, BL Cheng, NQ Steven, AC Watson, MS Cunningham, C Le Deuff, RM Renault, T AF Davison, AJ Trus, BL Cheng, NQ Steven, AC Watson, MS Cunningham, C Le Deuff, RM Renault, T TI A novel class of herpesvirus with bivalve hosts SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID SIMPLEX-VIRUS TYPE-1; CHANNEL CATFISH VIRUS; HATCHERY-REARED LARVAE; CRASSOSTREA-GIGAS; CRYOELECTRON MICROSCOPY; SEQUENCE COMPARISONS; OYSTER HERPESVIRUS; CAPSID STRUCTURE; PACIFIC OYSTERS; BINDING-PROTEIN AB Ostreid herpesvirus 1 (OsHV-1) is the only member of the Herpesviridae that has an invertebrate host and is associated with sporadic mortality in the Pacific oyster (Crassostrea gigas) and other bivalve species. Cryo-electron microscopy of purified capsids revealed the distinctive T = 16 icosahedral structure characteristic of herpesviruses, although the preparations examined lacked pentons. The gross genome organization of OsHV-1 was similar to that of certain mammalian herpesviruses (including herpes simplex virus and human cytomegalovirus), consisting of two invertible unique regions (U-L, 167-8 kbp; U-S, 3-4 kbp) each flanked by inverted repeats (TRL/IRL, 7-6 kbp; TRS/IRS, 9-8 kbp), with an additional unique sequence (X, 1.5 kbp) between IRL and IRS. Of the 124 unique genes predicted from the 207 439 bp genome sequence, 38 were members of 12 families of related genes and encoded products related to helicases, inhibitors of apoptosis, deoxyuridine triphosphatase and RING-finger proteins, in addition to me m bran e-associated proteins. Eight genes in three of the families appeared to be fragmented. Other genes that did not belong to the families were predicted to encode DNA polymerase, the two subunits of ribonucleotide reductase, a helicase, a primase, the ATPase subunit of terminase, a RecB-like protein, additional RING-like proteins, an ion channel and several other membrane-associated proteins. Sequence comparisons showed that OsHV-1 is at best tenuously related to the two classes of vertebrate herpesviruses (those associated with mammals, birds and reptiles, and those associated with bony fish and amphibians). OsHV-1 thus represents a third major class of the herpesviruses. C1 Inst Virol, MRC, Virol Unit, Glasgow G11 5JR, Lanark, Scotland. NIAMSD, Imaging Sci Lab, Ctr Informat Technol, NIH, Bethesda, MD 20892 USA. NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. IFREMER, Lab Genet & Pathol, F-17390 La Tremblade, France. RP Davison, AJ (reprint author), Inst Virol, MRC, Virol Unit, Church St, Glasgow G11 5JR, Lanark, Scotland. EM a.davison@vir.gla.ac.uk RI RENAULT, Tristan/H-6405-2011 NR 78 TC 128 Z9 244 U1 4 U2 33 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD JAN PY 2005 VL 86 BP 41 EP 53 DI 10.1099/vir.0.80382-0 PN 1 PG 13 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 888QT UT WOS:000226390000006 PM 15604430 ER PT J AU Von Eschenbach, AC AF Von Eschenbach, AC TI Special Issue - The National Cancer Institute's Cancer Information Service: A New Generation of Service and Research to the Nation - Foreword SO JOURNAL OF HEALTH COMMUNICATION LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Von Eschenbach, AC (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2005 VL 10 SU 1 BP 5 EP 5 DI 10.1080/10810730500257614 PG 1 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 988DD UT WOS:000233570700002 ER PT J AU Bright, MA AF Bright, MA TI The National Cancer Institute's Cancer Information Service: A new generation of service and research to the nation SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID AFRICAN-AMERICAN SMOKERS; OUTREACH PROGRAM; IMPACT; INTERVENTION; EXPERIENCE AB The National Cancer Institute (NCI), the nation's leading agency for cancer information and research, mandated by the U. S. Congress to provide accurate, up-to-date information about cancer to all segments of the U.S. population, established the Cancer Information Service (CIS) on July 1, 1975. Using a two-pronged approach, the telephone information service and education programs for the public and health professionals, the CIS was designed to maximize its reach. In 1982, the CIS implemented three tools: the Call Record Form to record data about each call to the service, a national user survey and a system of national test calls. These resulted in a rich data source and all infrastructure that allowed collaborative health communications research with the CIS to emerge later in the decade. As the CIS embarks on a new generation of service to the nation, it is now characterized by three vital components that advance the NCI's overall mission of cancer prevention and control: a Partnership Program, Multichannel Contact Centers, and a Health Communications Research Program. C1 NCI, Off Canc Informat Serv, NIH, Bethesda, MD 20892 USA. RP Bright, MA (reprint author), NCI, Off Canc Informat Serv, NIH, 6116 Execut Blvd,Room 3048,MSC 8322, Bethesda, MD 20892 USA. EM brightma@mail.nih.gov NR 34 TC 9 Z9 9 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2005 VL 10 SU 1 BP 7 EP 13 DI 10.1080/10810730500263687 PG 7 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 988DD UT WOS:000233570700003 PM 16377597 ER PT J AU Squiers, L Rutten, LJF Treiman, K Bright, MA Hesse, B AF Squiers, L Rutten, LJF Treiman, K Bright, MA Hesse, B TI Cancer patients' information needs across the cancer care continuum: Evidence from the cancer information service SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID SUPPORT; COMMUNICATION; PROSTATE; IMPACT; BREAST; WOMEN AB This study examines the information needs of cancer patients who contacted the National Cancer Institute's (NCI's) Cancer Information Service (CIS) via a toll-free telephone number Records from 19,030 calls received from cancer patients between September 2002 and August 2003 were analyzed to determine differences in subjects of interaction (main topics of inquiry and discussion) for subgroups of patients based on demographic characteristics and stage along the cancer care continuum (pretreatment, in-treatinent, post-treatment, recurrence). Females were more likely than males to inquire about cancer screening/diagnosis, support services, psychosocial issues, and general cancer site information, but they were less likely to seek specific cancer treatment information. Older patients were more likely than younger patients to seek specific treatment information, but they were less interested in support services, psychosocial issues, and prevention/risk factors. Compared with White callers, Hispanics and most minorities were more likely to seek support service information, and African Americans were more likely to have questions related to psychosocial issues. Compared with patients in treatment, patients in recurrence were more likely to seek specific treatment information; patients not in treatment were more likely to seek medical referral information; and patients in post-treatment ivere more likely to seek screening/diagnosis and prevention/risk risk/factor information. Findings will help the CIS and other cancer-focused organizations address the distinct information needs of different subsets of cancer patients. C1 NCI, Canc Informat Serv, Rockville, MD 20850 USA. NCI, Canc Prevent Fellowship Program, Div Canc Prevent & Hlth Commun, Bethesda, MD 20892 USA. NCI, Informat Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Hlth Commun & Informat Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. RP Squiers, L (reprint author), NCI, Canc Informat Serv, 6116 Execut Blvd, Rockville, MD 20850 USA. OI Hesse, Bradford/0000-0003-1142-1161 NR 24 TC 71 Z9 71 U1 2 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2005 VL 10 SU 1 BP 15 EP 34 DI 10.1080/10810730500263620 PG 20 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 988DD UT WOS:000233570700004 PM 16377598 ER PT J AU Stoddard, JL Delucchi, KL Munoz, RF Collins, NM Stable, EJP Augustson, E Lenert, LL AF Stoddard, JL Delucchi, KL Munoz, RF Collins, NM Stable, EJP Augustson, E Lenert, LL TI Smoking cessation research via the Internet: A feasibility study SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID FAGERSTROM TOLERANCE QUESTIONNAIRE; WORLD-WIDE-WEB; NICOTINE DEPENDENCE; SMOKERS; INTERVENTIONS; ABSTINENCE; PROGRAM; SPANISH; MAIL AB To reverse the present stagnation in progress toward reduced smoking rates, new widely accessible treatment methods for smoking cessation must be developed and evaluated with large groups of smokers. We tested the feasibility of conducting a smoking cessation study over the Internet using a brief self-help educational intervention. Through a direct e-mail sent from a large health information web site (WebMD), and with our presence on the Internet, we recruited 538 adult smokers to the study. Most participants (90.5%) completed all baseline questionnaires. Questionnaires showed acceptable to good reliability and were comparable with studies using paper-and-pencil methods. Participants appeared to be highly dependent on nicotine. Forty-two percent indicated being ready to quit smoking at baseline. At 1-month follow-up, 42.8% of baseline participants returned a complete follow-up questionnaire, 40% of whom indicated having made a serious quit attempt, and 8.3% of whom indicated 7-day abstinence. Most follow-up participants rated the site as at least somewhat helpful to quitting (74.9%) and reported at least a slight increased intention to quit smoking over baseline (67.3%). While Internet-enabled self-help interventions for smoking cessation are able to reach large numbers of smokers interested in quitting smoking, additional procedures are needed to retain these users for treatment and follow-up assessments. C1 Univ Calif San Francisco, Ctr Comprehens Canc, Dept Psychiat, San Francisco, CA 94143 USA. San Francisco Gen Hosp, Latino Mental Hlth Res Program, San Francisco, CA USA. Univ Calif San Francisco, Med Effectiveness Res Ctr Diverse Populat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. RP Munoz, RF (reprint author), Univ Calif San Francisco, Ctr Comprehens Canc, Dept Psychiat, Box 0852, San Francisco, CA 94143 USA. FU NIDA NIH HHS [P50DA09253] NR 45 TC 37 Z9 37 U1 4 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PD JAN-FEB PY 2005 VL 10 IS 1 BP 27 EP 41 DI 10.1080/10810730590904562 PG 15 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 903PP UT WOS:000227438400003 PM 15764442 ER PT J AU Bright, MA Fleisher, L Thomsen, C Morra, ME Marcus, A Gehring, W AF Bright, MA Fleisher, L Thomsen, C Morra, ME Marcus, A Gehring, W TI Exploring e-health usage and interest among cancer information service users: The need for personalized interactions and multiple channels remains SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article AB Since searching for health information is among the most popular uses of the Internet, we analyzed a survey of 6,019 callers to the National Cancer Institute's (NCI's) Cancer Information Service (CIS) to assess Internet usage and interest in technologies to access health and cancer information. Findings suggest that about 40% of CIS callers used the Internet to obtain cancer information and of these, only about 20% found all the information they sought. Nearly 33% of Internet users called the CIS to discuss information found on the Internet; most (>90%) reported that the CIS was helpful. Those who sought cancer information on the Internet were more likely to call the CIS about this information if they found all or most of the information they were seeking, compared with those who found some or little of the information. New, communication services endorsed by most CIS callers included e-mails from an information specialist and telephone support from the CIS while on the Internet. The survey, results indicate the importance of multiple access points, both traditional and technology based, and that there is still a need for more traditional, personalized forms of health communication. A crucial question is how best to harness and integrate these new; technologies within the current. generation of mediated health information systems. C1 NCI, Off Canc Informat Serv, NIH, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Hlth Commun & Publ Hlth Program, Philadelphia, PA 19111 USA. NIH, Off Commun & Publ Liaison, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. Morra Commun, Milford, CT USA. Univ Colorado, Ctr Canc, AMC Canc Ctr, Ctr Behav Res, Denver, CO 80202 USA. Cooper Inst Denver, Golden, CO USA. RP Bright, MA (reprint author), NCI, Off Canc Informat Serv, NIH, 6116 Execut Blvd,Room 3049,MSC 8322, Bethesda, MD 20892 USA. FU NCI NIH HHS [2P0-1 CA 057586-09] NR 23 TC 31 Z9 31 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2005 VL 10 SU 1 BP 35 EP 52 DI 10.1080/10810730500265609 PG 18 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 988DD UT WOS:000233570700005 PM 16377599 ER PT J AU Talosig-Garcia, M Davis, SW AF Talosig-Garcia, M Davis, SW TI Information-seeking behavior of minority breast cancer patients: An exploratory study SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID INTERNET; NEEDS; WOMEN; PREFERENCES; IMPACT AB Few population-based studies have been conducted with minority breast cancer patients in the United States to understand their information-seeking behaviors. We examined the resources minority breast cancer patients used and the extent to which the Internet was being utilized by Hispanic and African American breast cancer patients. A random sample of 388 Hispanic and African American breast cancer female patients was obtained from the Sacramento Cancer Surveillance Program in California. Various survey and data collection tools were researched and adapted to create the 44-item questionnaire. Subjects were asked to participate in a telephone interview. Of the 388 cases, 74% (n = 287) consented to participate in our study. Sixty-three percent (n = 181) received cancer-related information at the time of their diagnosis; 58% reported that a health care professional provided them with this information. Only 17% of study respondents had ever used the Internet. The top 3 sources for cancer information were books, brochures, and pamphlets (98%); doctor or other health professionals (97%); and spouse or partner, family members, friends, or all of these (62%). None of the respondents indicated accessing the National Cancer Institute's cancer.gov website. Minority breast cancer patients were using the Internet for cancer-related information at a very low rate. C1 NCI, Canc Informat Serv, No Calif Canc Ctr, Fremont, CA 94538 USA. RP Davis, SW (reprint author), NCI, Canc Informat Serv, No Calif Canc Ctr, 2201 Walnut Ave,Suite 280, Fremont, CA 94538 USA. EM sdavis@nccc.org NR 26 TC 34 Z9 34 U1 2 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2005 VL 10 SU 1 BP 53 EP 64 DI 10.1080/10810730500263638 PG 12 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 988DD UT WOS:000233570700006 PM 16377600 ER PT J AU Latimer, AE Katulak, NA Mowad, L Salovey, P AF Latimer, AE Katulak, NA Mowad, L Salovey, P TI Motivating cancer prevention and early detection behaviors using psychologically tailored messages SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID MATCHING HEALTH MESSAGES; PHYSICAL-ACTIVITY; RANDOMIZED-TRIAL; MAMMOGRAPHY UTILIZATION; VEGETABLE CONSUMPTION; INFORMATION-SERVICE; MHLC SCALES; INTERVENTION; STYLES; NUTRITION AB Tailoring health messages to make them salient to recipients is a strategy to motivate cancer prevention and early defection behaviors. Various tactics call be used to tailor health materials; our approach involves tailoring messages to individual differences in the psychological processes by which people understand health information. To summarize out-tailoring approach, we review findings from six field experiments (four published, two pending publication) conducted in collaboration with the National Cancer Institute's (NCI's) Cancer Information Service (CIS) examining the utility of psychologically tailored messages. Messages were tailored to individual variability in the following: (a) need for cognition, (b) monitor/blunting coping style, (c) health locus of control, and (d) regulatory focus. Collectively, the findings suggest that, as hypothesized, messages congruent with the recipients' psychological style of health information processing (i.e., matched messages) are more persuasive in promoting screening mammography and fruit and vegetable consumption than mismatched messages. This line of research provides evidence for the utility of psychological tailoring as a health communication strategy and direction for developing effective health messages in a variety of settings. C1 Yale Univ, Dept Psychol, New Haven, CT 06520 USA. Yale Univ, Ctr Canc, Natl Canc Inst, Canc Informat Serv, New Haven, CT USA. RP Salovey, P (reprint author), Yale Univ, Dept Psychol, POB 208205, New Haven, CT 06520 USA. EM peter.salovey@yale.edu FU NCI NIH HHS [R01 CA068427, R01-CA68427]; NIDA NIH HHS [P50-DA1334]; NIMH NIH HHS [P01-MH/DA 56826] NR 43 TC 33 Z9 33 U1 4 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2005 VL 10 SU 1 BP 137 EP 155 DI 10.1080/10810730500263364 PG 19 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 988DD UT WOS:000233570700011 PM 16377605 ER PT J AU Perocchia, RS Rapkin, B Hodorowski, JK Davis, NL McFarlane, AR Carpenter, R AF Perocchia, RS Rapkin, B Hodorowski, JK Davis, NL McFarlane, AR Carpenter, R TI Raising awareness of on-line cancer information: Helping providers empower patients SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID HEALTH-CARE; INTERNET AB While the digital divide remains a special problem in health care, providers' reluctance to refer patients to the Internet is an equally important problem. The Bridging the Digital Divide Project: Your Access to Cancer Information was designed with two target audiences in mind-consumers and health care providers. A total of 256 providers from varied health care settings enrolled in workshops over a 10-month period (2001-2002). Results suggest differences in awareness and use of on-line cancer information among providers and confirm that many providers need to become more comfortable with referring patients to on-line information. At completion of the workshops, all participants reported an increased awareness of cancer information websites, increased confidence in making judgments about the reliability and appropriateness of the sites, an increased willingness to discuss Internet information sources with patients and their family members, and an increased awareness of and intention to use the CIS. Providers from the community hospital were more likely than other groups to report that what they had learned about the Internet was helpful and that their comfort level using the Internet had increased. Partnerships between providers and the CIS may help to further increase this comfort level, ultimately benefiting cancer patients. C1 Mem Sloan Kettering Canc Ctr, Natl Canc Inst, Canc Informat Serv, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. RP Perocchia, RS (reprint author), Mem Sloan Kettering Canc Ctr, Natl Canc Inst, Canc Informat Serv, 1275 York Ave, New York, NY 10021 USA. EM perocchr@mskcc.org OI Hodorowski, Julie/0000-0003-3587-2135 NR 20 TC 9 Z9 9 U1 2 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2005 VL 10 SU 1 BP 157 EP 172 DI 10.1080/10810730500265575 PG 16 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 988DD UT WOS:000233570700012 PM 16377606 ER PT J AU Gustafson, DH McTavish, FM Stengle, W Ballard, D Jones, E Julesberg, K McDowell, H Landucci, G Hawkins, R AF Gustafson, DH McTavish, FM Stengle, W Ballard, D Jones, E Julesberg, K McDowell, H Landucci, G Hawkins, R TI Reducing the digital divide for low-income women with breast cancer: A feasibility study of a population-based intervention SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID PRIMARY-CARE; TRENDS; CHESS AB A fundamental challenge to helping underserved women and their families cope with breast cancer is providing them with easily accessible, reliable health care information and support. This is especially trite for low-income families living in rural areas where resources are few, and frequently distant as well as low-income families in urban areas where access to information and support can be complex and overwhelming. The Internet is one mechanism that has tremendous potential to help these families cope with breast cancer. This article describes a feasibility test of the potential for the National Cancer Institute's (NCI's) Cancer Information Service (CIS) to provide access to an Internet-based system that has been shown to improve quality of life for underserved breast cancer patients. The test was conducted in rural Wisconsin (low socioeconomic status [SES] Caucasian women) and in Detroit, Michigan (low SES African American women), and compares the effectiveness of several different dissemination strategies. Using these results we propose a model for how CIS telephone and partnership program services could efficiently disseminate such information and support systems. In doing so we believe that important steps can be taken to close the digital divide that separates low-income families from the resources they need to effectively face cancer. This is the first of two articles coming from this study. A companion article reports on an evaluation of the use and impact of this system on the women who were given access to it. C1 Univ Wisconsin, Ctr Hlth Syst Res & Anal, Madison, WI 53726 USA. Natl Canc Inst, MW Canc Informat Serv, Detroit, MI USA. Natl Canc Inst, N Cent Canc Informat Serv, Madison, WI USA. RP Gustafson, DH (reprint author), Univ Wisconsin, Ctr Hlth Syst Res & Anal, 610 Walnut St,WARF Bldg Off 1119, Madison, WI 53726 USA. EM dhgustaf@wisc.edu NR 23 TC 39 Z9 40 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2005 VL 10 SU 1 BP 173 EP 193 DI 10.1080/10810730500263281 PG 21 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 988DD UT WOS:000233570700013 PM 16377607 ER PT J AU Gustafson, DH McTavish, FM Stengle, W Ballard, D Hawkins, R Shaw, BR Jones, E Julesberg, K McDowell, H AF Gustafson, DH McTavish, FM Stengle, W Ballard, D Hawkins, R Shaw, BR Jones, E Julesberg, K McDowell, H TI Use and impact of eHealth system by low-income women with breast cancer SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID SOCIAL SUPPORT; FUNCTIONAL ASSESSMENT; COMPUTER SUPPORT; SURVIVAL AB This article is the second of a two-part series reporting oil a population-based study intended to use an eHealth system to examine the feasibility of reaching underserved women with breast cancer (Gustafson, McTavish et al., Reducing the digital divide for low-income women with breast cancer, 2004; Madison Center for Health Systems Research and Analysis, University of Wisconsin; Comprehensive Health Enhancement Support System [CHESS]) and determine how they use the system and what impact it had on them. Participants included women recently diagnosed with breast cancer whose income was at or below 250% of poverty level and were living in rural Wisconsin (n = 144; all Caucasian) or Detroit (n = 85; all African American). Because this was a population-based study all 229 participants received CHESS. A comparison group of patients (n = 51) with similar demographics was drawn from a separate recently completed randomized clinical trial. Use rates (e.g., frequency and length of use as well as type of use) as well as impact oil several dimensions of quality of life and participation in health care are reported. Low-income subjects in this study logged on and spent more time oil CHESS than more affluent women in a previous study. Urban African Americans used information and analysis services more and communication services less than rural Caucasians. When all low-income women from this study are combined and compared with a low-income control group from another study, the CHESS group was superior to that control group in 4 of 8 outcome variables at both statistically and practically significant levels (social support, negative emotions, participation in health care, and information competence). When African Americans and Caucasians are separated the control group's sample size becomes 30 and 21 thus reducing power. Statistical significance is retained, however, in all four outcomes for Caucasians and in two of four for African Americans. Practical significance is retained for all four outcomes. We conclude that an eHealth system like CHESS will be used extensively and have a positive impact on low-income women with breast cancer. C1 Univ Wisconsin, Ctr Hlth Syst Res & Anal, Madison, WI 53706 USA. Natl Canc Inst, Canc Informat Serv, MW Canc Informat Serv, Detroit, MI USA. Natl Canc Inst, Canc Informat Serv, N Cent Canc Informat Serv, Madison, WI USA. RP Gustafson, DH (reprint author), Univ Wisconsin, Ctr Hlth Syst Res & Anal, Madison, WI 53706 USA. EM dhgustaf@wisc.edu NR 39 TC 91 Z9 94 U1 1 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2005 VL 10 SU 1 BP 195 EP 218 DI 10.1080/10810730500263257 PG 24 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 988DD UT WOS:000233570700014 PM 16377608 ER PT J AU Marcus, AC Heimendinger, J Berman, E Strecher, V Bright, MA Allen, AR Davis, SW Julesberg, K Mowad, LZ Nguyen, LH Perocchia, R Thomsen, C AF Marcus, AC Heimendinger, J Berman, E Strecher, V Bright, MA Allen, AR Davis, SW Julesberg, K Mowad, LZ Nguyen, LH Perocchia, R Thomsen, C TI A case study in dissemination: Lessons learned from a pilot study involving the National Cancer Institute's Cancer Information Service SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID EFFICACY; HEALTH; TRANSITION; MODEL AB The Cancer Information Service Research Consortium (CISRC) was funded by the National Cancer Institute to disseminate as a pilot study a longitudinally tailored print intervention to promote the 5 A Day for Better Health program among callers to the National Cancer Institute's Cancer Information Service (CIS). Using a one group (intervention-only) study design, 1,022 eligible CIS callers were enrolled to receive the intervention consisting of four mailings of tailored print materials over a 3-month period Program evaluation focused on process and implementation evaluation, including adherence to the baseline interviews by CIS information specialists based on live-call monitoring (n = 55 eligible callers), and the timeliness of the intervention mailouts (4,088 scheduled inailouts). Adherence to the baseline interviews by CIS information specialists was extremely high, exceeding 90% for all indicators of quality control. Of the 4,088 intervention mailings, 75% occurred oil or before the target date, while 95% occurred within 21 days of the target date. All delays in the scheduled mailouts occurred in the first mailing, due to changes made in the production process (batch printing of all tailored print materials at baseline). This change required additional system upgrades and more intensive and time-consuming quality control than originally anticipated, which was exacerbated by the faster-than-expected accrual of eligible participants. Based on this pilot study, the CIS is now positioned for widespread dissemination of the 5 A Day tailored print intervention. Several key lessons learned are also identified to facilitate the transition from research to dissemination. C1 AMC Canc Res Ctr, Ctr Behav & Community Studies, Denver, CO 80214 USA. Aspen Syst Corp, Rockville, MD USA. Univ Michigan, Hlth Media Res Lab, Ann Arbor, MI 48109 USA. NCI, Canc Informat Serv, Bethesda, MD 20892 USA. W Virginia Univ, Mary Babb Randolph Canc Ctr, Canc Informat Serv, Mid Altantci Reg, Morgantown, WV 26506 USA. No Calif Canc Ctr, Calif Reg, Canc Informat Serv, Union City, CA USA. Univ Wisconsin, Ctr Canc, N Cent Reg, Canc Informat Serv, Madison, WI USA. Yale Univ, Ctr Canc, New Haven, CT USA. Univ Texas, MD Anderson Canc Ctr, Canc Informat Serv, S Cent Reg, Houston, TX 77030 USA. Mem Sloan Kettering Canc Ctr, New York Reg, Canc Informat Serv, New York, NY 10021 USA. NCI, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Marcus, AC (reprint author), AMC Canc Res Ctr, Ctr Behav & Community Studies, 1600 Pierce St, Denver, CO 80214 USA. EM marcusa@amc.org NR 17 TC 5 Z9 5 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2005 VL 10 SU 1 BP 219 EP 233 DI 10.1080/10810730500257689 PG 15 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 988DD UT WOS:000233570700015 PM 16377609 ER PT J AU Marcus, AC Morra, ME Bright, MA Fleisher, L Kreps, G Perocchia, R AF Marcus, AC Morra, ME Bright, MA Fleisher, L Kreps, G Perocchia, R TI The CIS model for collaborative research in health communications: A brief retrospective from the current generation of research SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID CANCER INFORMATION-SERVICE; VEGETABLE CONSUMPTION; RANDOMIZED-TRIAL; INCREASE FRUIT; INTERVENTION; CALLERS; CONSORTIUM; TELEPHONE AB The Cancer Information Service (CIS) of the National Cancer Institute (NCI) is the premiere organization for providing cancer information to the nation. The CIS provides a stellar example of how a service organization dedicated to health communications also can serve as a laboratory for research. This journey by the CIS into health communication research is described briefly along with the current generation Of research summarized in this issue of the Journal of Health Communication (JHC). The CIS model for collaborative research is presented as an exemplar that other service organizations might embrace as a strategic tool for quality improvement in health communications. C1 AMC Canc Res Ctr, Ctr Behav & Community Studies, Denver, CO 80214 USA. Morra Commun, Milford, CT USA. NCI, Canc Informat Serv, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Hlth Commun & Publ Hlth Program, Philadelphia, PA 19111 USA. George Mason Univ, Dept Commun, Fairfax, VA 22030 USA. Mem Sloan Kettering Canc Ctr, Natl Canc Inst, Canc Informat Serv, New York, NY 10021 USA. RP Marcus, AC (reprint author), AMC Canc Res Ctr, Ctr Behav & Community Studies, 1600 Pierce St, Denver, CO 80214 USA. EM marcusa@amc.org NR 26 TC 10 Z9 10 U1 2 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2005 VL 10 SU 1 BP 235 EP 245 DI 10.1080/10810730500263612 PG 11 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 988DD UT WOS:000233570700016 PM 16377610 ER PT J AU Belfer, I Buzas, B Hipp, H Phillips, G Taubman, J Lorincz, I Evans, C Lipsky, RH Enoch, MA Max, MB Goldman, D AF Belfer, I Buzas, B Hipp, H Phillips, G Taubman, J Lorincz, I Evans, C Lipsky, RH Enoch, MA Max, MB Goldman, D TI Haplotype-based analysis of alpha 2A, 2B, and 2C adrenergic receptor genes captures information on common functional loci at each gene SO JOURNAL OF HUMAN GENETICS LA English DT Article DE single-nucleotide polymorphism; insertion/deletion polymorphism; linkage disequilibrium; haplotype; alpha 2-adrener1gic receptors ADRA2A; ADRA2B; ADRA2C ID ALPHA(2B)-ADRENERGIC RECEPTOR GENE; 3RD INTRACELLULAR LOOP; ALPHA(2)-ADRENERGIC RECEPTORS; LINKAGE DISEQUILIBRIUM; ACID DELETION; HUMAN GENOME; HYPERTENSION; POLYMORPHISM; HERITABILITY; BLOCKS AB The alpha 2-adrenergic receptors (alpha(2)-AR) mediate physiological effects of epinephrine and norepinephrine. Three genes encode alpha(2)-AR subtypes carrying common functional polymorphisms (ADRA2A Asn251Lys, ADRA2B Ins/Del301-303 and ADRA2C Ins/Del322-325). We genotyped these functional markers plus a panel of single nucleotide polymorphisms evenly spaced over the gene regions to identify gene haplotype block structure. A total of 24 markers were genotyped in 96 Caucasians and 96 African Americans. ADRA2A and ADRA2B each had a single haplotype block at least 11 and 16 kb in size, respectively, in both populations. ADRA2C had one haplotype block of 10 kb in Caucasians only. For the three genes, haplotype diversity and the number of common haplotypes were highest in African Americans, but a similar number of markers (3-6) per block was sufficient to capture maximum diversity in either population. For each of the three genes, the haplotype was capable of capturing the information content of the known functional locus even when that locus was not genotyped. The alpha(2)-AR haplotype maps and marker panels are useful tools for genetic linkage studies to detect effects of known and unknown alpha(2)-AR functional loci. C1 NIH, Rockville, MD 20852 USA. Natl Inst Dental & Craniofacial Res, Pain & Neurosensory Mechanisms Branch, Bethesda, MD 20892 USA. Natl Inst Alcohol Abuse & Alcoholism, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Belfer, I (reprint author), NIH, 12420 Parklawn Dr,Suite 451,MSC 8110, Rockville, MD 20852 USA. EM ibelfer@mail.nih.gov RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Lipsky, Robert/0000-0001-7753-1473; Hipp, Heather/0000-0002-1089-3928 FU NIAAA NIH HHS [Z01 AA000301]; NIDCR NIH HHS [Z01 DE00366] NR 29 TC 32 Z9 33 U1 0 U2 1 PU SPRINGER TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 1435-232X J9 J HUM GENET JI J. Hum. Genet. PY 2005 VL 50 IS 1 BP 12 EP 20 DI 10.1007/s10038-004-0211-y PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 893BD UT WOS:000226693400003 PM 15592690 ER PT J AU Svetkey, LP Erlinger, TP Vollmer, WM Feldstein, A Cooper, LS Appel, LJ Ard, JD Elmer, PJ Harsha, D Stevens, VJ AF Svetkey, LP Erlinger, TP Vollmer, WM Feldstein, A Cooper, LS Appel, LJ Ard, JD Elmer, PJ Harsha, D Stevens, VJ TI Effect of lifestyle modifications on blood pressure by race, sex, hypertension status, and age SO JOURNAL OF HUMAN HYPERTENSION LA English DT Article DE blood pressure; hypertension; lifestyle; DASH; weight loss; diet ID CLINICAL-TRIAL; DIETARY PATTERNS; SODIUM REDUCTION; WEIGHT-LOSS; NONPHARMACOLOGIC INTERVENTIONS; SUBGROUP ANALYSIS; DASH DIET; PHASE-II; PREVENTION; SENSITIVITY AB Recommendations for control of high blood pressure (BP) emphasize lifestyle modification, including weight loss, reduced sodium intake, increased physical activity, and limited alcohol consumption. The Dietary Approaches to Stop Hypertension (DASH) dietary pattern also lowers BP. The PREMIER randomized trial tested multicomponent lifestyle interventions on BP in demographic and clinical subgroups. Participants with above-optimal BP through stage 1 hypertension were randomized to an Advice Only group or one of two behavioural interventions that implement established recommendations (Est) or established recommendations plus DASH diet (Est plus DASH). The primary outcome was change in systolic BP at 6 months. The study population was 810 individuals with an average age of 50 years, 62% women, 34% African American (AA), 95% overweight/obese, and 38% hypertensive. Participants in all the three groups made lifestyle changes. Mean net reductions in systolic (S) BP in the Est intervention were 1.2 mmHg in AA women, 6.0 in AA men, 4.5 in non-AA women, and 4.2 in non-AA men. The mean effects of the Est Plus DASH intervention were 2.1, 4.6, 4.2, and 5.7 mmHg in the four race-sex subgroups, respectively. BP changes were consistently greater in hypertensives than in nonhypertensives, although interaction tests were nonsignificant. The Est intervention caused statistically significant BP reductions in individuals over and under age 50. The Est Plus DASH intervention lowered BP in both age groups, and significantly more so in older individuals. In conclusion, diverse groups of people can adopt multiple lifestyle changes that can lead to improved BP control and reduced CVD risk. C1 Duke Univ, Med Ctr, Duke Hypertens Ctr, Durham, NC 27710 USA. Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27710 USA. Johns Hopkins Med Ctr, Welch Prevent Ctr, Baltimore, MD USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Med, Dept Nutr Sci, Birmingham, AL 35294 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. RP Svetkey, LP (reprint author), Duke Univ, Med Ctr, Duke Hypertens Ctr, Box 3075, Durham, NC 27710 USA. EM svetk001@mc.duke.edu FU NHLBI NIH HHS [UO1 HL60570, UO1 HL60574, UO1 HL62828, UO1 HL60571, UO1 HL60573] NR 28 TC 93 Z9 96 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD JAN PY 2005 VL 19 IS 1 BP 21 EP 31 DI 10.1038/sj.jhh.1001770 PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 880EX UT WOS:000225772900003 PM 15385946 ER PT J AU Kumanyika, SK Cook, NR Cutler, JA Belden, L Brewer, A Cohen, JD Hebert, PR Lasser, VI Raines, J Raczynski, J Shepek, L Diller, L Whelton, PK Yamamoto, M AF Kumanyika, SK Cook, NR Cutler, JA Belden, L Brewer, A Cohen, JD Hebert, PR Lasser, VI Raines, J Raczynski, J Shepek, L Diller, L Whelton, PK Yamamoto, M CA Hypertension Prevention Collaborat TI Sodium reduction for hypertension prevention in overweight adults: further results from the Trials of Hypertension Prevention Phase II SO JOURNAL OF HUMAN HYPERTENSION LA English DT Article DE primary prevention; blacks; dietary change; women; blood pressure ID ISOLATED SYSTOLIC HYPERTENSION; RANDOMIZED CONTROLLED-TRIALS; REDUCED DIETARY-SODIUM; BLOOD-PRESSURE; NONPHARMACOLOGIC INTERVENTIONS; WEIGHT-LOSS; ANGIOTENSINOGEN GENOTYPE; OLDER PERSONS; UNITED-STATES; ELDERLY TONE AB Sodium reduction is efficacious for primary prevention of hypertension, but the feasibility of achieving this effect is unclear. The objective of the paper is detailed analyses of adherence to and effects of the sodium reduction intervention among overweight adults in the Trials of Hypertension Prevention, Phase II. Sodium reduction (comprehensive education and counselling about how to reduce sodium intake) was tested vs no dietary intervention (usual care) for 36-48 months. A total of 956 white and 203 black adults, ages 30-54 years, with diastolic blood pressure 83-89 mmHg, systolic blood pressure (SBP) <140 mmHg, and body weight 110-165% of gender-specific standard weight were included in the study. At 36 months, urinary sodium excretion was 40.4 mmol/24 h (24.4%) lower in sodium reduction compared to usual care participants (P < 0.0001), but only 21% of sodium reduction participants achieved the targeted level of sodium excretion below 80 mmol/24 h. Adherence was positively related to attendance at face-to-face contacts. Net decreases in SBP at 6, 18, and 36 months of 2.9 (P < 0.001), 2.0 (P < 0.001), and 1.3 (P = 0.02) mmHg in sodium reduction vs usual care were associated with an overall 18% lower incidence of hypertension (P = 0.048); were relatively unchanged by adjustment for ethnicity, gender, age, and baseline blood pressure, BMI, and sodium excretion; and were observed in both black and white men and women. From these beneficial but modest results with highly motivated and extensively counselled individuals, sodium reduction sufficient to favourably influence the population blood pressure distribution will be difficult to achieve without food supply changes. C1 Univ Penn, Sch Med, CCEB, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. Univ Calif Davis, Sch Med, Davis, CA 95616 USA. Univ Tennessee, Memphis, TN USA. St Louis Univ, Sch Med, St Louis, MO 63103 USA. Yale Univ, Sch Med, New Haven, CT USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Alabama, Birmingham, AL USA. Univ Arkansas Med Sci, Coll Publ Hlth, Little Rock, AR 72205 USA. St Elizabeth Hosp, So Illinois Heart Inst, Belleville, IL USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Kumanyika, SK (reprint author), Univ Penn, Sch Med, CCEB, 8th Floor Blockley Hall, Philadelphia, PA 19104 USA. EM skumanyi@cceb.med.upenn.edu FU NHLBI NIH HHS [HL 37924, HL 37904, HL 37907, HL 37854, HL 37884, HL 37906, HL 37853, HL 37852, HL 37849, HL 37899] NR 41 TC 44 Z9 44 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD JAN PY 2005 VL 19 IS 1 BP 33 EP 45 DI 10.1038/sj.jhh.1001774 PG 13 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 880EX UT WOS:000225772900004 PM 15372064 ER PT J AU Cook, NR Kumanyika, SK Cutler, JA Whelton, PK AF Cook, NR Kumanyika, SK Cutler, JA Whelton, PK CA Hypertension Prevention Collaborat TI Dose-response of sodium excretion and blood pressure change among overweight, nonhypertensive adults in a 3-year dietary intervention study SO JOURNAL OF HUMAN HYPERTENSION LA English DT Article DE blood pressure; sodium excretion; dose-response; dietary intervention; primary prevention; population; cardiovascular disease ID HYPERTENSION PREVENTION; PUBLIC-HEALTH; PHASE-I; TRIALS; METAANALYSIS; REDUCTION; SALT; PREVALENCE; INTERSALT AB A cross-sectional dose-response relationship between sodium intake and blood pressure (BP) has been demonstrated, but evidence for a graded longitudinal effect is limited. Evaluation of BP response to sodium reduction was assessed in a 3-year lifestyle dietary intervention trial. BP changes at 18 and 36 months after enrollment were analysed according to concurrent quantitative changes in sodium excretion and by categories of success in sodium reduction among 1157 men and women, ages 30-54 years, with a diastolic BP (DBP) 83-89 mmHg, systolic BP (SBP) <140 mmHg, body weight 110-165% of sex-specific standard weight, and valid baseline urinary sodium excretion. Participants were randomized to a Sodium Reduction intervention (n = 581) or Usual Care (n = 576). From a 187 mmol/24 h baseline mean sodium excretion, net decreases were 44 mmol/24 h at 18 months and 38 mmol/24 h at 36 months in Sodium Reduction vs Usual Care. Corresponding net decreases in SBP/DBP were 2.0/1.4 mmHg at 18 months, and 1.7/0.9 mmHg at 36 months. Significant dose-response trends in BP change over quintiles of achieved sodium excretion were seen at both 18 (SBP and DBP) and 36 (SBP only) months; effects appeared stronger among those maintaining sodium reduction. Estimated SBP decreases per 100 mmol/24 h reduction in sodium excretion at 18 and 36 months were 2.2 and 1.3 mmHg before and 7.0 and 3.6 mmHg after correction for measurement error, respectively. DBP changes were smaller and nonsignificant at 36 months. In conclusion, incremental decreases in BP with lower sodium excretion were observed in these overweight nonhypertensive individuals. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, E Boston, MA 02215 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NHLBI, Bethesda, MD 20892 USA. Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. RP Cook, NR (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave, E Boston, MA 02215 USA. EM ncook@rics.bwh.harvard.edu FU NHLBI NIH HHS [HL 37852, HL 37849, HL 37854, HL 37884, HL 37904, HL 37906, HL 37907, HL 37924, HL37853, HL37899] NR 27 TC 13 Z9 14 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD JAN PY 2005 VL 19 IS 1 BP 47 EP 54 DI 10.1038/sj.jhh.1001775 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 880EX UT WOS:000225772900005 PM 15343354 ER PT J AU Vollmer, WM Appel, LJ Svetkey, LP Moore, TJ Vogt, TM Conlin, PR Proschan, M Harsha, D AF Vollmer, WM Appel, LJ Svetkey, LP Moore, TJ Vogt, TM Conlin, PR Proschan, M Harsha, D CA DASH Collaborative Res Grp TI Comparing office-based and ambulatory blood pressure monitoring in clinical trials SO JOURNAL OF HUMAN HYPERTENSION LA English DT Article DE blood pressure; blood pressure monitoring; ambulatory; clinical trials; methodology ID HYPERTENSIVE PATIENTS; DIETARY PATTERNS; REPRODUCIBILITY; RESTRICTION; VALUES AB Ambulatory blood pressure monitoring (ABPM) is commonly used in clinical trials. Yet, its ability to detect blood pressure (BP) change in comparison to multiple office-based measurements has received limited attention. We recorded ambulatory and five daily pairs of random zero (RZ) BPs pre- and post-intervention on 321 adult participants in the multicentre Dietary Approaches to Stop Hypertension trial. Treatment effect estimates measured by ambulatory monitoring were similar to those measured by RZ and did not differ significantly for waking vs 24-h ambulatory measurements. For systolic BP, the standard deviations of change in mean 24-h ambulatory BP (8.0 mmHg among hypertensives and 6.0 mmHg among nonhypertensives) were comparable to or lower than the corresponding standard deviations of change in RZ-BP based on five daily readings (8.9 and 5.9 mmHg). The standard deviations of change for mean waking ambulatory BP (8.7 and 6.7 mmHg) were comparable to those obtained using three to four daily RZ readings. Results for diastolic BP were qualitatively similar. Ambulatory monitoring was more efficient (ie, a smaller sample size could detect a given BP change) than three to four sets of daily RZ readings and required fewer clinic visits. The average of 33 ambulatory BP readings during the waking hours had an efficiency comparable to that from the mean of four daily pairs of RZ-BPs. Participants readily accepted the ABPM devices, and their use requires less staff training. ABPM provides a useful alternative to RZ-BP measurements in clinical trials. C1 Kaiser Permanente Ctr Hlth Res, Portland, OR 97227 USA. Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. Duke Univ, Med Ctr, Duke Hypertens Ctr, Durham, NC USA. Duke Univ, Med Ctr, Sarah W Stedman Ctr Nutr Studies, Durham, NC USA. Boston Univ, Boston, MA 02215 USA. Kaiser Permanente Ctr Hlth Res, Honolulu, HI USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Rockville, MD USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. RP Vollmer, WM (reprint author), Kaiser Permanente Ctr Hlth Res, 3800 N Interstate Ave, Portland, OR 97227 USA. EM william.vollmer@kpchr.org FU NCRR NIH HHS [RR00722, RR02635]; NHLBI NIH HHS [HL02642, HL50968, HL50972, HL50977, HL50981, HL50982] NR 32 TC 23 Z9 23 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD JAN PY 2005 VL 19 IS 1 BP 77 EP 82 DI 10.1038/sj.jhh.1001772 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 880EX UT WOS:000225772900009 PM 15361888 ER PT J AU Zamisch, M Moore-Scott, B Su, D Lucas, PJ Manley, N Richie, ER AF Zamisch, M Moore-Scott, B Su, D Lucas, PJ Manley, N Richie, ER TI Ontogeny and regulation of IL-7-expressing thymic epithelial cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COMMON LYMPHOID PROGENITORS; POLYMERASE CHAIN-REACTION; CYTOKINE GENE-EXPRESSION; RECEPTOR-DEFICIENT MICE; TCR-GAMMA-LOCUS; T-CELL; IL-7 RECEPTOR; THYMOCYTE DEVELOPMENT; STROMAL CELLS; MOUSE THYMUS AB Epithelial cells in the thymus produce IL-7, an essential cytokine that promotes the survival, differentiation, and proliferation of thymocytes. We identified IL-7-expressing thymic epithelial cells (TECs) throughout ontogeny and in the adult mouse thymus by in situ hybridization analysis. IL-7 expression is initiated in the thymic fated domain of the early primordium by embryonic day 11.5 and is expressed in a Foxn1-independent pathway. Marked changes occur in the localization and regulation of IL-7-expressing TECs during development. IL-7-expressing TECs are present throughout the early thymic rudiment. In contrast, a major population of IL-7-expressing TECs is localized to the medulla in the adult thymus. Using mouse strains in which thymocyte development is arrested at various stages, we show that fetal and postnatal thymi differ in the frequency and localization of IL-7-expressing TECs. Whereas IL-7 expression is initiated independently of hemopoietic-derived signals during thymic organogenesis, thymocyte-derived signals play an essential role in regulating IL-7 expression in the adult TEC compartment. Moreover, different thymocyte subsets regulate the expression of IL-7 and keratin 5 in adult cortical epithelium, suggesting that despite phenotypic similarities, the cortical TEC compartments of wild-type and RAG-1(-/-) mice are developmentally and functionally distinct. C1 Univ Texas, MD Anderson Canc Ctr, Sci Pk Res Div, Smithville, TX 78957 USA. Univ Texas, Grad Sch Biomed Sci, Houston, TX 77225 USA. Univ Georgia, Dept Genet, Athens, GA 30602 USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Richie, ER (reprint author), Univ Texas, MD Anderson Canc Ctr, Sci Pk Res Div, POB 389, Smithville, TX 78957 USA. EM erichie@odin.mdacc.tmc.edu FU NIAID NIH HHS [AI 055001, AI 041543]; NIEHS NIH HHS [ES 07784] NR 66 TC 76 Z9 76 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 2005 VL 174 IS 1 BP 60 EP 67 PG 8 WC Immunology SC Immunology GA 881HB UT WOS:000225852900010 PM 15611228 ER PT J AU Wu, LX La Rose, J Chen, L Neale, C Mak, T Okkenhaug, K Wange, R Rottapel, R AF Wu, LX La Rose, J Chen, L Neale, C Mak, T Okkenhaug, K Wange, R Rottapel, R TI CD28 regulates the translation of Bcl-x(L) via the phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL-ACTIVATION; PROTEIN-KINASE B; MESSENGER-RNA; KAPPA-B; COSTIMULATORY SIGNAL; MAMMALIAN TARGET; UP-REGULATION; C-FLIP; 3-KINASE; PHOSPHORYLATION AB In concert with the TCR, CD28 promotes T cell survival by regulating the expression of the antiapoptotic protein Bel-x(L). The mechanism by which CD28 mediates the induction of Bcl-x(L) remains unknown. We show that although signaling through the TCR is sufficient to stimulate transcription of Bcl-x(L) mRNA, CD28, by activating PI3K and mammalian target of rapalmycin, provides a critical signal that regulates the translation of Bcl-x(L) transcripts. We observe that CD28 induced 4E-binding protein-1 phosphorylation, an inhibitor of the translational machinery, and that CD28 costimulation directly augmented the translation of a Bcl-x(L) 5'-untranslated region reporter construct. Lastly, costimulation by CD28 shifted the distribution of Bcl-x(L) mRNA transcripts from the pretranslation complex to the translationally active polyribosomes. These results demonstrate that CD28 relieves the translational inhibition of Bcl-x(L) in a PI3K/mammalian target of rapamycin-dependent manner. C1 Princess Margaret Hosp, Ontario Canc Inst, Div Expt Therapeut, Toronto, ON M5G 2M9, Canada. Univ Toronto, Dept Immunol, Toronto, ON, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. Univ Toronto, Dept Med, Toronto, ON, Canada. Babraham Inst, Cambridge, England. NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD USA. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. RP Rottapel, R (reprint author), Princess Margaret Hosp, Ontario Canc Inst, Div Expt Therapeut, 610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM rottapel@uhnres.utoronto.ca RI Okkenhaug, Klaus/D-5149-2012 OI Okkenhaug, Klaus/0000-0002-9432-4051 NR 60 TC 38 Z9 39 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 2005 VL 174 IS 1 BP 180 EP 194 PG 15 WC Immunology SC Immunology GA 881HB UT WOS:000225852900022 PM 15611240 ER PT J AU Lekstrom-Himes, JA Kuhns, DB Alvord, WG Gallin, JI AF Lekstrom-Himes, JA Kuhns, DB Alvord, WG Gallin, JI TI Inhibition of human neutrophil IL-8 production by hydrogen peroxide and dysregulation in chronic granulomatous disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; INTERLEUKIN-8 GENE-EXPRESSION; TRANSCRIPTION FACTORS AP-1; NF-KAPPA-B; CHEMOTACTIC FACTORS; RESPIRATORY BURST; ESCHERICHIA-COLI; EPITHELIAL-CELLS; LEUKOTRIENE B-4; OXIDANT STRESS AB The innate immune response to bacterial infections includes neutrophil chemotaxis and activation, but regulation of inflammation is less well understood. Formyl peptides, byproducts of bacterial metabolism as well as mitochondrial protein biosynthesis, induce neutrophil chemotaxis, the generation of reactive oxygen intermediates (1101), and the production of the neutrophil chemoattractant, IL-8. Patients with chronic granulomatous disease (CGD) exhibit deficient generation of ROI and hydrogen peroxide and susceptibility to bacterial and fungal pathogens, with associated dysregulated inflammation and widespread granuloma formation. We show in this study that in CGD cells, fMLF induces a 2- to 4-fold increase in IL-8 production and a sustained IL-8 mRNA response compared with normal neutrophils. Moreover, normal neutrophils treated with catalase (H2O2 scavenger) or diphenyleneiodonium chloride (NADPH oxidase inhibitor) exhibit IL-8 responses comparable to those of CGD neutrophils. Addition of hydrogen peroxide or an H2O2-generating system suppresses the sustained IL-8 mRNA and increased protein production observed in CGD neutrophils. These results indicate that effectors downstream of the activation of NADPH oxidase negatively regulate IL-8 mRNA in normal neutrophils, and their absence in CGD cells results in prolonged IL-8 mRNA elevation and enhanced IL-8 levels. ROI may play a critical role in regulating inflammation through this mechanism. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. SAIC Frederick Inc, Clin Serv Program, Frederick, MD 21702 USA. NCI, Data Management Serv, Frederick, MD 21702 USA. RP Gallin, JI (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Room 2C146,10 Ctr Dr, Bethesda, MD 20892 USA. EM jgallin@nih.gov FU NCI NIH HHS [N01 CO 12400] NR 29 TC 61 Z9 62 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 2005 VL 174 IS 1 BP 411 EP 417 PG 7 WC Immunology SC Immunology GA 881HB UT WOS:000225852900047 PM 15611265 ER PT J AU Hashimoto, K Sheller, JR Morrow, JD Collins, RD Goleniewska, K O'Neal, J Zhou, WS Ji, SQ Mitchell, DB Graham, BS Peebles, RS AF Hashimoto, K Sheller, JR Morrow, JD Collins, RD Goleniewska, K O'Neal, J Zhou, WS Ji, SQ Mitchell, DB Graham, BS Peebles, RS TI Cyclooxygenase inhibition augments allergic inflammation through CD4-dependent, STAT6-independent mechanisms SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AIRWAY HYPERRESPONSIVENESS; CYTOKINE SECRETION; PROSTAGLANDIN E(2); SENSITIZED MICE; DEFICIENT MICE; ASTHMA; INTERLEUKIN-13; CELLS; IL-4; PROFILES AB Nonselective cyclooxygenase (COX) inhibition during the development of allergic disease in a murine model causes an increase in type 2 cytokines and lung eosinophilia; however, the mechanisms responsible for this augmented allergen-induced inflammation have not been examined. Ab depletion of CD4 and CD8 cells revealed that the heightened allergic inflammation caused by COX inhibition was CD4, but not CD8, dependent. Allergen sensitization and airway challenge alone led to undetectable levels of IL-5 and IL-13 in the lungs of IL-4, IL-4Ralpha, and STAT6 knockout (KO) mice, but COX inhibition during the development of allergic inflammation resulted in wild-type levels of IL-5 and IL-13 and heightened airway eosinophilia in each of the three KO mice. These results indicate that the effect of COX inhibition was independent of signaling through IL-4, IL-4Ralpha, and STAT6. However, whereas COX inhibition increased IgE levels in allergic wild-type mice, IgE levels were undetectable in IL-4, IL-4Ralpha and STAT6 KO mice, suggesting that IL-13 alone is not a switch factor for IgE synthesis in this model. These results illustrate the central role played by products derived from the COX pathway in the regulation of allergic immune responses. C1 Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA. LINCO Res, St Charles, MO 63304 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Peebles, RS (reprint author), Vanderbilt Univ, Med Ctr, T-1217 MCN, Nashville, TN 37232 USA. EM stokes.peebles@vanderbilt.edu FU NCI NIH HHS [CA 77839]; NHLBI NIH HHS [R01 HL 069949]; NIAID NIH HHS [R01 AI 054660]; NIDDK NIH HHS [DK 26657, DK 48831]; NIGMS NIH HHS [GM 15431] NR 27 TC 25 Z9 26 U1 1 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 2005 VL 174 IS 1 BP 525 EP 532 PG 8 WC Immunology SC Immunology GA 881HB UT WOS:000225852900061 PM 15611279 ER PT J AU Zhou, JH Dudley, ME Rosenberg, SA Robbins, PF AF Zhou, JH Dudley, ME Rosenberg, SA Robbins, PF TI Persistence of multiple tumor-specific T-Cell clones is associated with complete tumor regression in a melanoma patient receiving adoptive cell transfer therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE melanoma; adoptive cell transfer; T-cell receptor beta chain variable regions; T-cell persistence; tumor antigens ID INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; ANTIGENS; IDENTIFICATION; INTERLEUKIN-2; IMMUNOTHERAPY; RECOGNITION; GAS7 AB The authors recently reported that adoptive immunotherapy with autologous tumor-reactive tumor infiltrating lymphocytes (TILs) immediately following a conditioning non-myeloablative chemotherapy regimen resulted in an enhanced clinical response rate in patients with metastatic melanoma. These observations led to the current studies, which are focused on a detailed analysis of the T-cell antigen reactivity as well as the in vivo persistence of T cells in melanoma patient 2098, who experienced a complete regression of all metastatic lesions in lungs and soft tissues following therapy. Screening of an autologous tumor cell cDNA library using transferred TILs resulted in the identification of novel mutated growth arrest-specific gene 7 (GAS7) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene transcripts. Direct sequence analysis of the expressed T-cell receptor beta chain variable regions showed that the transferred TILs contained multiple T-cell clonotypes, at least six of which persisted in peripheral blood for a month or more following transfer. The persistent T cells recognized both the mutated GAS7 and GAPDH. These persistent tumor-reactive T-cell clones were detected in tumor cell samples obtained from the patient following adoptive cell transfer and appeared to be represented at higher levels in the tumor sample obtained 1 month following transfer than in the peripheral blood obtained at the same time. Overall, these results indicate that multiple tumor-reactive T cells can persist in the peripheral blood and at the tumor site for prolonged times following adoptive transfer and thus may be responsible for the complete tumor regression in this patient. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), Room 3-3940,CRC,Bldg 10,10 Ctr Dr MSC1201, Bethesda, MD 20892 USA. EM sar@mail.nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 26 TC 82 Z9 87 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD JAN-FEB PY 2005 VL 28 IS 1 BP 53 EP 62 DI 10.1097/00002371-200501000-00007 PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 884LT UT WOS:000226087300007 PM 15614045 ER PT J AU Robbins, JB Schneerson, R Trollfors, B Sato, H Sato, Y Rappuoli, R Keith, JM AF Robbins, JB Schneerson, R Trollfors, B Sato, H Sato, Y Rappuoli, R Keith, JM TI The diphtheria and pertussis components of diphtheria-tetanus toxoids-pertussis vaccine should be genetically inactivated mutant toxins SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID LYMPHOCYTOSIS-PROMOTING FACTOR; ACELLULAR PERTUSSIS; BORDETELLA-PERTUSSIS; WHOOPING-COUGH; FILAMENTOUS HEMAGGLUTININ; CONTROLLED TRIAL; RESPIRATORY-INFECTION; NUCLEOTIDE-SEQUENCE; HOUSEHOLD EXPOSURE; HYDROGEN-PEROXIDE AB Replacement of cellular with acellular pertussis (aP) vaccines has considerably reduced the systemic reactions observed with diphtheria-tetanus toxoids-pertussis vaccine but has not eliminated the extensive swelling ( sometimes involving an entire limb) observed after the fifth injection of diphtheria-tetanus toxoids- aP (DTaP) vaccine. This local reaction, which is likely an Arthus hypersensitivity reaction caused by high levels of antibodies reacting with DTaP vaccine, could discourage its use in adults, who serve as the major reservoir of pertussis for infants. That a critical level of antibodies to pertussis toxin is both essential and sufficient to prevent infection with Bordetella pertussis is derived from data from animal and clinical studies, including data showing the similarities between the immunity induced by diphtheria and pertussis toxoids. The genetically inactivated diphtheria and pertussis mutant toxins are more immunogenic and, therefore, induce comparable levels of antitoxin at lower protein levels than do the formalin-treated native toxins. Replacement of the diphtheria and aP components with these improved antigens will reduce the amount of protein in DTaP vaccine and, most likely, the incidence and severity of local reactions in teenagers and adults. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Univ Gothenburg, Dept Pediat, Gothenburg, Sweden. Chiron Vaccines, Siena, Italy. RP Robbins, JB (reprint author), NICHHD, NIH, Bldg 31,Rm 2A-25, Bethesda, MD 20892 USA. EM robbinsjo@mail.nih.gov NR 100 TC 24 Z9 26 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 2005 VL 191 IS 1 BP 81 EP 88 DI 10.1086/426454 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 877JF UT WOS:000225564000013 PM 15593007 ER PT J AU Bariae, I Fumiae, K Vugrek, O Aeuk, M Maradin, M Glenn, B Wagner, C Stabler, S Schulze, A Rados, M Sarnavka, V Buist, N Mudd, SH AF Bariae, I. Fumiae, K. Vugrek, O. Aeuk, M. Maradin, M. Glenn, B. Wagner, C. Stabler, S. Schulze, A. Rados, M. Sarnavka, V. Buist, N. Mudd, S. H. TI S-ADENOSYLHOMOCYSTEINE (ADOHCY) HYDROLASE DEFICIENCY: MYOPATHY SEEMS TO BE CONGENITAL SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 [Bariae, I.; Fumiae, K.; Aeuk, M.; Maradin, M.; Rados, M.; Sarnavka, V.] Univ Zagreb, Univ Hosp Ctr, Zagreb, 80202, Croatia. [Vugrek, O.] Inst Ruoer Boskoviae, Zagreb, Croatia. [Glenn, B.; Wagner, C.] Vanderbilt Univ, Nashville, TN 97201 USA. [Stabler, S.] Univ Colorado, Denver, CO 20892 USA. [Schulze, A.] Univ Childrens Hosp, Heidelberg, Germany. [Buist, N.] Oregon Hlth & Sci Univ, Portland, OR USA. [Mudd, S. H.] NIMH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PY 2005 VL 28 SU 1 BP 76 EP 76 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 460TC UT WOS:000267210400153 ER PT J AU Acosta, M Munasinghe, J Theodore, WH Gibson, KM Gupta, M Pearl, P Rogawski, MA AF Acosta, M. Munasinghe, J. Theodore, W. H. Gibson, K. M. Gupta, M. Pearl, P. Rogawski, M. A. TI BRAIN MRI AND HISTOLOGY IN A MURINE MODEL OF INHERITED SUCCINIC SEMIALDEHYDE DEHYDROGENASE (SSADH) DEFICIENCY SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 [Acosta, M.; Theodore, W. H.; Rogawski, M. A.] NINDS, Epilepsy Res Lab, NIH, Bethesda, MD 20892 USA. [Munasinghe, J.] NINDS, Mouse Imaging Facil, NIH, Bethesda, MD 20892 USA. [Gibson, K. M.; Gupta, M.] Oregon Hlth & Sci Univ, Clin Biochem Genet Lab, Portland, OR 97201 USA. [Acosta, M.; Pearl, P.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PY 2005 VL 28 BP 234 EP 234 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 460TC UT WOS:000267210400469 ER PT J AU Kim-Shapiro, DB Gladwin, MT Patel, RP Hogg, N AF Kim-Shapiro, DB Gladwin, MT Patel, RP Hogg, N TI The reaction between nitrite and hemoglobin: the role of nitrite in hemoglobin-mediated hypoxic vasodilation SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article DE nitrite; hemoglobin; hypoxia; vasodilation ID S-NITROSOHEMOGLOBIN; HYDROGEN-PEROXIDE; ACID-BASE; OXIDE; OXIDATION; MECHANISM; DEOXYHEMOGLOBIN; OXYHEMOGLOBIN; INVOLVEMENT; MYOGLOBIN AB The reaction between nitrite and hemoglobin has been studied for over a century. However, recent evidence indicating nitrite is a latent vasodilatory agent that can be activated by its reaction with deoxyhemoglobin has led to renewed interest in this reaction. In this review we survey, in the context of our own recent studies, the chemical reactivity of nitrite with oxyhemoglobin, deoxyhemoglobin and methemoglobin, and place these reactions in both a physiological and pharmacological/therapeutic context. (C) 2004 Elsevier Inc. All rights reserved. C1 Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Free Rad Res Ctr, Milwaukee, WI 53226 USA. Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA. NIDDK, Dept Crit Care Med, Biol Chem Lab, NIH, Bethesda, MD USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ Alabama, Ctr Free Rad Biol, Birmingham, AL 35294 USA. RP Hogg, N (reprint author), Med Coll Wisconsin, Dept Biophys, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM nhogg2@mcw.edu OI Patel, Rakesh/0000-0002-1526-4303 FU NHLBI NIH HHS [HL58091, HL70146, R01 HL058091]; NIGMS NIH HHS [GM55792] NR 44 TC 101 Z9 103 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD JAN PY 2005 VL 99 IS 1 BP 237 EP 246 DI 10.1016/j.jinorgbio.2004.10.034 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 891AZ UT WOS:000226555000019 PM 15598504 ER PT J AU Marx, SJ Stratakis, CA AF Marx, SJ Stratakis, CA TI Multiple endocrine neoplasia - Introduction SO JOURNAL OF INTERNAL MEDICINE LA English DT Article DE multiple endocrine neoplasia; genetic counselling; tumorigenesis; MEN1; MEN2; HRPT2; VHL; Carney Complex; PRKAR1A; hyperparathyroid; cyclic AMP AB Each multiple endocrine neoplasia (MEN) syndrome expresses striking features of hormone oversecretion from its own characteristic group of tissues. Additional expressions include non-hormonal tumours in each MEN syndrome and selected cancers in some syndromes. The complexity of its stereotyped features results in difficult management issues that often justify cooperation across multiple specialties. MEN syndromes, though rare, have long received intense study as models for more common diseases. The syndromal nature often with a large pedigree has promoted recent discovery of the main gene that differs for each of the six MEN syndromes. Each mutant gene has been introduced into clinical decision-making and into further clarification of tumorigenesis. This mini-symposium is related to the 9th International Workshop on Multiple Endocrine Neoplasia in June 2004; it consists of six manuscripts. They report new developments in clinical practices and in basic understandings about this rapidly advancing field. C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Marx, SJ (reprint author), NIDDK, Metab Dis Branch, NIH, Bld 10,Rm 9C-101, Bethesda, MD 20892 USA. EM stephenm@intra.niddk.nih.gov NR 13 TC 30 Z9 30 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD JAN PY 2005 VL 257 IS 1 BP 2 EP 5 DI 10.1111/j.1365-2796.2004.01419.x PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 892UA UT WOS:000226674300001 PM 15606371 ER PT J AU Pacak, K Ilias, I Adams, KT Eisenhofer, G AF Pacak, K Ilias, I Adams, KT Eisenhofer, G TI Biochemical diagnosis, localization and management of pheochromocytoma: focus on multiple endocrine neoplasia type 2 in relation to other hereditary syndromes and sporadic forms of the tumour SO JOURNAL OF INTERNAL MEDICINE LA English DT Article DE computerized tomography; magnetic resonance imaging; metanephrines; multiple endocrine neoplasia type 2; pheochromocytoma; radionuclide imaging ID MALIGNANT PHEOCHROMOCYTOMA; SOMATOSTATIN RECEPTORS; LAPAROSCOPIC SURGERY; RET PROTOONCOGENE; WILD-TYPE; PET; METAIODOBENZYLGUANIDINE; SCINTIGRAPHY; PARAGANGLIOMAS; ADRENALECTOMY AB Approximately 50% of patients with multiple endocrine neoplasia (MEN) 2A or 2B develop pheochromocytoma. These tumours are almost exclusively benign and localized in the adrenal glands. About one-third are bilateral at initial diagnosis. Amongst patients with pheochromocytoma. those with MEN 2A have subtler symptoms compared to those with sporadic disease. Since pheochromocytomas in patients with MEN 2 often secrete catecholamines episodically (but metabolize them continuously to metanephrines), the first choice for biochemical diagnosis is the measurement of free metanephrines in plasma, with urinary fractionated metanephrines being the second choice. In patients with pheochromocytomas that produce exclusively normetanephrine, MEN2 can be excluded. In patients with biochemically proven MEN2-related pheochromocytoma, anatomical imaging of the adrenals (with either computerized tomography or magnetic resonance) should be obtained next. Functional imaging with specific ligands (e.g. scintigraphy with [I-123]-metaiodobenzylguanidine or, if available, positron emission tomography with [F-18]-fluorodopamine, [C-18]-dihydroxyphenylalanine, [C-11]-adrenaline or [C-11]-hydroxyephedrine) may then be particularly useful in patients with distorted anatomy from previous surgery. in cases of equivocal biochemical data despite high clinical suspicion for a tumour. to rule out multifocal disease, or where there is suspicion of metastatic disease (e.g. tumours larger than 5 cm). Laparoscopic surgery is the treatment of choice and subtotal (cortical-sparing) adrenalectomy is the procedure of choice in bilateral pheochromocytomas. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Patras, Sch Med, Dept Pharmacol, GR-26110 Patras, Greece. Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, NIH, Bethesda, MD USA. RP Ilias, I (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,CRC,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM iliasi@mail.nih.gov NR 67 TC 46 Z9 48 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD JAN PY 2005 VL 257 IS 1 BP 60 EP 68 DI 10.1111/j.1365-2796.2004.01425.x PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 892UA UT WOS:000226674300007 PM 15606377 ER PT J AU Kalinin, AE Kalinin, AE Aho, M Uitto, J Aho, S AF Kalinin, AE Kalinin, AE Aho, M Uitto, J Aho, S TI Breaking the connection: Caspase 6 disconnects intermediate filament-binding domain of periplakin from its actin-binding N-terminal region SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE actin; apoptosis; caspases; intermediate filaments; periplakin ID PLAKIN FAMILY; PARANEOPLASTIC PEMPHIGUS; DESMOSOMAL PROTEINS; F-ACTIN; PROMOTES APOPTOSIS; CORNIFIED ENVELOPE; LIGAND-BINDING; CELL-DEATH; KERATIN 18; KINASE-B AB Periplakin is a member of the plakin family of cytolinkers that connect cytoskeletal networks to each other as well as to the cell junctional complexes. Here, we demonstrate a direct molecular interaction between actin and periplakin. Furthermore, the oligomerization state of periplakin was shown to determine specificity of its binding to intermediate filaments (IF) in vitro. Both the filament association and the cell membrane localization of periplakin were confirmed in the cells overexpressing human periplakin. Double labeling of the N- and C-terminally tagged periplakin revealed unexpected lack of co-localization of periplakin ends in a confluent culture, and separation of the periplakin ends was even more pronounced in apoptotic cells. Western analysis revealed that after induction of apoptosis, periplakin becomes cleaved close to its C-terminal tail. Only the distinct cleavage products, but not the full-length periplakin, were present in the cells detached from the solid support during the apoptotic process. We show that caspase 6 cleaves periplakin at an unconventional recognition site, amino acid sequence TVAD. Thus, the separation of periplakin ends disconnects the actin-binding head-rod domain from the IF-binding C-terminal domain. We show that specific cleavage products co-exist with the full-length periplakin in cells, suggesting physiological consequences due to their altered binding specificities. C1 Thomas Jefferson Univ, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA. NIAMSD, Skin Biol Lab, NIH, Bethesda, MD USA. RP Aho, S (reprint author), Thomas Jefferson Univ, Dept Dermatol & Cutaneous Biol, 233 S 10th St,BLSB 422, Philadelphia, PA 19107 USA. EM sirpa.aho@jefferson.edu FU PHS HHS [R01 33588] NR 66 TC 14 Z9 15 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2005 VL 124 IS 1 BP 46 EP 55 DI 10.1111/j.0022-202X.2004.23507.x PG 10 WC Dermatology SC Dermatology GA 882PR UT WOS:000225951300010 PM 15654952 ER PT J AU Lisziewicz, J Trocio, J Whitman, L Varga, G Xu, JQ Bakare, N Erbacher, P Fox, C Woodward, R Markham, P Arya, S Behr, JP Lori, F AF Lisziewicz, J Trocio, J Whitman, L Varga, G Xu, JQ Bakare, N Erbacher, P Fox, C Woodward, R Markham, P Arya, S Behr, JP Lori, F TI DermaVir: A novel topical vaccine for HIV/AIDS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE cellular immunity; dendritic cells; skin; therapy; topical vaccine ID STRUCTURED TREATMENT INTERRUPTIONS; HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL-DRUG-THERAPY; MODIFIED DENDRITIC CELLS; CYTOTOXIC T-LYMPHOCYTES; CHRONIC HIV-1 INFECTION; LONG-TERM SURVIVORS; IN-VIVO; IMMUNE-RESPONSES; IMMUNOLOGICAL CONSEQUENCES AB Human immunodeficiency virus (HIV) vaccines have the potential to improve antiretroviral drug treatment by inducing cytotoxic killing of HIV-infected cells. Prophylactic vaccines utilize new antigens to initiate immunity; however, in HIV-infected individuals the load of viral antigen is not the limiting factor for the restoration of immune responses. Here we describe a novel immunization strategy with DermaVir that improves viral antigen presentation using dendritic cells (DC). DermaVir contains a distinctive plasmid DNA expressing all HIV proteins except integrase to induce immune responses with broad specificity. The DNA is formulated to a mannosilated particle to target antigen-presenting cells and to protect the DNA from intracellular degradation. After topical application, DermaVir-transduced cells migrate from the skin to the draining lymph node and interdigitate as DermaVir-expressing, antigen-presenting DC. We compared the immunogenicity of topical and ex vivo DC-based DermaVir vaccinations in naive rhesus macaques. Both vaccinations induced simian immunodeficiency virus-specific CD4 helper and CD8 memory T cells detected by an in vivo skin test and an in vitro intracellular cytokine-based assay. Topical DermaVir vaccination represents an improvement upon existing ex vivo DC-based immunization technologies and may provide a new therapeutic option for HIV-infected patients. C1 Res Inst Genet & Human Therapy, Washington, DC 20007 USA. Genet Immun LLC, Washington, DC USA. PolyPlus Transfect, Illkirch Graffenstaden, France. Mol Histol Labs Inc, Gaithersburg, MD USA. Adv BioSci Labs Inc, Rockville, MD USA. NCI, NIH, Bethesda, MD 20892 USA. Fac Pharm, Lab Chim Genet, Illkirch Graffenstaden, France. RP Lisziewicz, J (reprint author), Res Inst Genet & Human Therapy, Washington, DC 20007 USA. EM lisziewj@geneticimmunity.com FU NIAID NIH HHS [N01-AI-15430] NR 69 TC 63 Z9 63 U1 0 U2 7 PU BLACKWELL PUBLISHING 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 2005 VL 124 IS 1 BP 160 EP 169 DI 10.1111/j.0022-202X.2004.23535.x PG 10 WC Dermatology SC Dermatology GA 882PR UT WOS:000225951300028 PM 15654970 ER PT J AU Hibbs, NT Lynch, JK Nelson, KB AF Hibbs, NT Lynch, JK Nelson, KB TI Risk of stroke in newborns in the United States. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Western Univ Hlth Sci, Coll Osteopath Med, Pomona, CA USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2005 VL 53 IS 1 SU S MA 239 BP S119 EP S119 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 890VR UT WOS:000226539700252 ER PT J AU Hibbs, NT Lynch, JK Nelson, KB AF Hibbs, NT Lynch, JK Nelson, KB TI Risk of stroke in newborns in the United States. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Western Univ Hlth Sci, Coll Osteopath Med, Pomona, CA USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2005 VL 53 IS 1 SU S MA 63 BP S88 EP S88 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 890VR UT WOS:000226539700077 ER PT J AU Hoffman, JL Martins, TB Augustine, NH Veasy, LG Musser, JM Hill, HR AF Hoffman, JL Martins, TB Augustine, NH Veasy, LG Musser, JM Hill, HR TI Analysis of antibody responses in patients with acute rheumatic fever employing a multi-plexed fluorescent immunoassay. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA. Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA. Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT USA. ARUP Inst Clin & Expt Pathol, Salt Lake City, UT USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. NIAID, Rocky Mt Lab, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2005 VL 53 IS 1 SU S MA 435 BP S154 EP S154 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 890VR UT WOS:000226539700448 ER PT J AU Niakan, A Shorr, RI Kritchevsky, SB Bush, A Cushman, W Simonsick, E Newman, AB Rooks, R Ding, J Rubin, S Harris, TB AF Niakan, A Shorr, RI Kritchevsky, SB Bush, A Cushman, W Simonsick, E Newman, AB Rooks, R Ding, J Rubin, S Harris, TB TI Does outpatient prescription drug benefit lead to better control of high blood pressure in older adults? SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Vet Affairs Med Ctr, Memphis, TN USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NIA, Baltimore, MD 21224 USA. Univ Pittsburgh, Pittsburgh, PA USA. Kent State Univ, Kent, OH 44242 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIH Hlth ABC Study, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2005 VL 53 IS 1 SU S MA 233 BP S294 EP S294 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 890VR UT WOS:000226539700753 ER PT J AU Ryder, KM Shorr, R Tylavsky, F Bush, A Bauer, D Simonsick, E Strotmeyer, E Harris, T AF Ryder, KM Shorr, R Tylavsky, F Bush, A Bauer, D Simonsick, E Strotmeyer, E Harris, T TI Low initiation of antifracture therapy in black women. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Tennessee, Memphis, TN USA. NIA, Bethesda, MD 20892 USA. RI Strotmeyer, Elsa/F-3015-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2005 VL 53 IS 1 SU S MA 341 BP S314 EP S314 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 890VR UT WOS:000226539700861 ER PT J AU Vazquez, BG Morrison, K Fitzpatrick, AL AF Vazquez, BG Morrison, K Fitzpatrick, AL TI E-mail evaluation of a course in HIV prevention for health professionals in Mexico and Latin America. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. Natl Inst Hlth, Multidisciplinary Int Res Training Program, Bethesda, MD USA. Inst Nacl Salud Publ, Cuernavaca, Morelos, Mexico. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2005 VL 53 IS 1 SU S MA 11 BP S79 EP S80 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 890VR UT WOS:000226539700025 ER PT J AU Schechter, AN Miller, FG AF Schechter, AN Miller, FG TI To publish or not to publish? SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Editorial Material ID CROSS-LINKED HEMOGLOBIN C1 NIDDKD, NIH, Mol Med Branch, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Schechter, AN (reprint author), NIDDKD, NIH, Mol Med Branch, Bethesda, MD 20892 USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 11 TC 2 Z9 2 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 2005 VL 145 IS 1 BP 9 EP 11 DI 10.1016/j.lab.2004.11.014 PG 3 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 893TA UT WOS:000226740900002 PM 15668655 ER PT J AU Madan, R Divanovic, S Atabani, SF Wahl, LM Hildeman, D Ma, XJ Karp, CL AF Madan, R Divanovic, S Atabani, SF Wahl, LM Hildeman, D Ma, XJ Karp, CL TI Regulation of the IL-12/23p40 promoter in primary human ARC SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-for-Leukocyte-Biology CY SEP 21-24, 2005 CL Sir William Dunn Sch Pathol, Oxford, ENGLAND SP Soc Leukocyte Biol HO Sir William Dunn Sch Pathol C1 Cincinnati Childrens Hosp Res Fdn, Cincinnati, OH USA. NIH, Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Cornell Univ, Weill Med Coll, New York, NY 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 2005 SU S MA 179 BP 72 EP 72 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 962PB UT WOS:000231743600178 ER PT J AU Cuesta, N Nhu, Q Zudaire, E Vogel, SN AF Cuesta, N Nhu, Q Zudaire, E Vogel, SN TI Role of IRF-2 in the regulation of apoptosis in macrophages SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-for-Leukocyte-Biology CY SEP 21-24, 2005 CL Sir William Dunn Sch Pathol, Oxford, ENGLAND SP Soc Leukocyte Biol HO Sir William Dunn Sch Pathol C1 Univ Maryland, Baltimore, MD 21201 USA. NIH, Bethesda, MD 20892 USA. RI Cuesta, Natalia/C-1358-2012; Cuesta, Natalia/J-7761-2015 OI Cuesta, Natalia/0000-0003-0809-2934 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 2005 SU S MA 190 BP 76 EP 76 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 962PB UT WOS:000231743600189 ER PT J AU Du, QZ Zhang, Q Ito, Y AF Du, QZ Zhang, Q Ito, Y TI Isolation and identification of phenolic compounds in the fruit of Benincasa hispida by HSCCC SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE countercurrent chromatography; Benincasa hispida; phenolic compounds; preparative separation ID COUNTERCURRENT CHROMATOGRAPHY; WAX GOURD; SEPARATION; COGN AB Separation of phenolic components from the fruit Benincasa hispida was conducted using high-speed countercuffent chromatography (HSCCC) with two solvent systems, n-hexane-n-butanol-methanol-water (10 : 16 : 5 : 20, v/v) and n-hexane-ethyl acetate-methanol-water (1 : 1 : 1 : 1, v/v). Three compounds, astilbin (120 mg), catechin (103 mg), and naringenin (79 mg) were obtained from the separation of 2 g of crude phenolic component extract of the fruit. Chemical structures of these three compounds were confirmed by electrospray ionization ion trap multiple mass spectrometry (ESI-MS) and NMR. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Hangzhou Univ Commerce, Inst Food & Biol Engn, Hangzhou, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Room 3334,50 South Dr MSC 8014, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov NR 13 TC 9 Z9 10 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 2005 VL 28 IS 1 BP 137 EP 144 DI 10.1081/JLC-200038620 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 886TM UT WOS:000226255600010 ER PT J AU Okunji, CO Iwu, MM Ito, Y AF Okunji, CO Iwu, MM Ito, Y TI Preparative separation of indole alkaloids from the rind of Picralima nitida (Stapf) T. Durand & H. Durand by pH-Zone-refining countercurrent chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE preparative separation; pH-zone-refining counter-current chromatography; indole alkaloids; Picralima nitida; anti-malarial activity; alstonine ID IN-VITRO; SEEDS AB Picralima nitida alkaloids have been shown to possess in vitro antimalarial activity comparable to the clinical antimalarial chloroquine and quinine. The in vitro IC50 values for these alkaloids ranged from 0.01 to 0.9 mug/mL against chloroquine-sensitive (136) and chloroquine-resistant (W2) strains of Plasmodium falciparum. As part of our continuing research aimed at identifying new antimalarial leads from African rain forest plants, we have been highly successful in employing pH-zone-refining counter-current chromatography (CCC) to separate and isolate the Picralima alkaloids. The separation was performed in two steps with a two-phase solvent system composed of tert-butyl methyl ether (MTBE)/acetonitrile/water (2: 2: 3, v/v), in which the lower phase was used as the mobile phase at a flow-rate of 2.0 mL min(-1) in the head-to-tail elution mode pH-zone-refining counter-current chromatography. The resulting fractions contained the alkaloids alstonine, akuammigine, akuammine, picraline, akuammine, akuammicine, picratidine were identified using thermospray liquid chromatography-mass spectrometry (LC-MS) and by TLC co-elution experiments with authentic samples. The application of pH-zone-refining CCC to perform successful separations at the multigram level will be discussed. The Picralima alkaloids may represent an entirely new antimalarial chemotype with possible pharmacokinetics advantages over the existing drugs. C1 NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. Bioresources Dev & Conservat Programme, Silver Spring, MD USA. Int Ctr Ethnomed & Drug Dev, Nsukka, Nigeria. Walter Reed Army Inst Res, Dept Med Chem, Div Expt Therapeut, Washington, DC USA. RP Ito, Y (reprint author), NHLBI, Ctr Biochem & Biophys, NIH, Bldg 50,Rm 3334, Bethesda, MD 20892 USA. EM itoy@nhlbi-nih.gov NR 22 TC 18 Z9 21 U1 3 U2 20 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 2005 VL 28 IS 5 BP 775 EP 783 DI 10.1081/JLC-200048915 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 904CH UT WOS:000227473200012 ER PT J AU Shinomiya, K Okada, T Ito, Y AF Shinomiya, K Okada, T Ito, Y TI Elutriation of blood cell components and mast cells by nonsynchronous coil planet centrifuge SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE nonsynchronous coil planet centrifuge; elutriation; blood cell separation; erythrocytes; mast cell separation; centrifugation ID ROTATING SEALS; SEPARATION; SYSTEMS AB The nonsynchronous coil planet centrifuge was applied to the separation of blood cell components and mast cells using a physiological buffer solution. The optimal separation of sheep blood samples was performed at the counterclockwise revolution and the clockwise rotation of coiled separation column by the head to tail elution mode. Under the high speed of revolution of 600-1000 rpm, sheep and human blood samples were completely separated and eluted into two peaks, where all cell components, other than erythrocytes such as platelets and leukocytes, were eluted at 0rpm and erythrocytes at 10rpm of coil rotation. The normal elution pattern was achieved at 800rpm of revolution for sheep blood and at 700rpm for human blood samples. The separation of mast cells, large cells with a high density, was also performed using an eluent composed of RPMI 1640 medium +10% FCS. Mast cells were satisfactorily separated from other cell components under a high speed revolution combined with a low speed of coil rotation (2-5 rpm). The overall results indicate that the nonsynchronous CPC can be effectively used for separation of blood cell components and mast cells according to their sedimentation rates. C1 Nihon Univ, Coll Pharm, Funabashi, Chiba 2748555, Japan. Aichi Med Univ, Dept Physiol, Aichi, 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 kshinomiya@pha.nihon-u.ac.jp NR 10 TC 2 Z9 2 U1 1 U2 1 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 2005 VL 28 IS 6 BP 835 EP 846 DI 10.1081/JLC-200051469 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 912TK UT WOS:000228102600003 ER PT J AU Chen, LJ Song, H Du, QZ Li, JR Ito, Y AF Chen, LJ Song, H Du, QZ Li, JR Ito, Y TI Analysis of flavonoids in the extracts from the seeds of Oroxylum indicum using high speed countercurrent chromatography/mass spectrometry SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE flavonoids; Oroxylum indicum; HSCCC-MS ID MASS-SPECTROMETRY; CCC AB The HSCCC was successfully interfaced with a mass spectrometer possessing APCI- and ESI-MS mode for the first time. The coupling system gave an excellent separation of ethyl acetate extract from the seeds of O. indicum using a solvent system composed of hexane-etbyl acetate-methanol-0.2% formic acid (1: 1.2: 1: 1); the online data of APCI-MS and APCI-MS-MS provided useful information for the identification of the compounds. C1 NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. W China Univ Med Sci, Univ Hosp 1, Ctr Biotherapy Canc & Canc Ctr, Huaxi Med Sch, Chengdu, Peoples R China. Sichuan Univ, Dept Pharmaceut & Bioengn, Chengdu, Peoples R China. Zhejiang Gongshang Univ, Inst Food & Biol Engn, Hangzhou, Peoples R China. RP Ito, Y (reprint author), NHLBI, Ctr Biochem & Biophys, NIH, Bldg 50,Rm 3334,50 S Dr MSC 8014, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov NR 7 TC 17 Z9 19 U1 1 U2 7 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 2005 VL 28 IS 10 BP 1549 EP 1555 DI 10.1081/JLC-200058350 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 939SP UT WOS:000230093000010 ER PT J AU Conway, WD Chadwick, LR Fong, HHS Farnsworth, NR Pauli, GF AF Conway, WD Chadwick, LR Fong, HHS Farnsworth, NR Pauli, GF TI Extra-column volume in CCC SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article; Proceedings Paper CT 3rd International Conference on Countercurrent Chromatography (CCC 2000) CY 2004 CL Tokyo, JAPAN DE CCC; countercurrent chromatography; extra-column volume; sample injection; coil-planet centrifuge; K; K-c; partition coefficient; distribution constant ID CHROMATOGRAPHY; CENTRIFUGE AB Countercurrent chromatography (CCC) is used by natural products and medicinal chemists for fractionation of extracts of flora and fauna to screen for pharmacological activity, and in isolating and purifying gram quantities of individual natural and synthetic compounds. The large extra-column volume in CCC apparatus, particularly in the coil-planet centrifuge designs employing an anti-twisting flow line assembly, may lead to errors in the calculation of the distribution ratios of eluting fractions. The effect of extra-column volume is to delay the time required for a peak to reach the detector. This delay is equal to the transit time of the extra-column volume plus half of the mobile-phase portion of the sample volume. The effect is negligible for columns of large volume (300 mL) but becomes more significant for small columns (15 mL) and for large sample volumes. Manual correction for the effect is very tedious, but results obtained using a generally applicable spreadsheet are presented and discussed. A second spreadsheet is also indicated wherein peak retention times, along with sample and extra-column volume, are entered for calculation of distribution constants, which are summarized on a single page convenient for entry in a notebook. C1 Univ Buffalo, Dept Pharmaceut Sci, Sch Pharm & Pharmaceut Sci, Buffalo, NY 14260 USA. Univ Illinois, NIH, Ctr Dietary Supplements Res, Chicago, IL USA. Univ Illinois, Dept Med Chem & Pharmacognosy, Chicago, IL USA. RP Conway, WD (reprint author), Univ Buffalo, Dept Pharmaceut Sci, Sch Pharm & Pharmaceut Sci, 569 Hochstetter Hall, Buffalo, NY 14260 USA. EM wdconway@buffalo.edu OI Pauli, Guido/0000-0003-1022-4326 NR 6 TC 11 Z9 11 U1 0 U2 1 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 2005 VL 28 IS 12-13 BP 1799 EP 1818 DI 10.1081/JLC-200063448 PG 20 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 955ZZ UT WOS:000231270000003 ER PT J AU Kobayashi, K Ohshima, H Shinomiya, K Ito, Y AF Kobayashi, K Ohshima, H Shinomiya, K Ito, Y TI Analysis of acceleration produced by planetary motion in a nonsynchronous coil planet centrifuge SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article; Proceedings Paper CT 3rd International Conference on Countercurrent Chromatography (CCC 2000) CY 2004 CL Tokyo, JAPAN DE countercurrent chromatography; nonsynchronous coil planet centrifuge; planetary motion; acceleration ID PROTEIN SEPARATION; CELL-SEPARATION; ROTATING SEALS AB The nonsynchronous coil planet centrifuge has a unique mode of planetary motion such that it provides freely adjustable coil rotation under a given centrifugal force field, and it produces an acceleration which fluctuates in a plane perpendicular to the axis of the holder. The two modes of planetary motion may be expressed as P-forward (coil rotation and revolution in the same direction) (revolution/rotation = clockwise CW/CW or counterclockwise CCW/CCW) and P-backward (coil rotation and revolution in the opposite directions) (revolution/rotation = CW/CCW or CCW/CW). The present study describes the analysis of acceleration produced by planetary motion in this apparatus. Our analysis is based on the equation for the absolute value of acceleration (A) in a given point on the column holder. A is calculated from each value obtained at the maximum and the minimum. The result indicated that the maximum value of A in P-forward is larger than that in P-backward under the same rotational rate, while the minimum value of A in P-forward is smaller than that in P-backward. A higher rotational rate increases the difference of the value between P-forward and P-backward. The overall results may support that the difference of maximum A and minimum A (Delta A) between P-forward and P-backward affects the retention of the stationary phase. Differences were observed experimentally in a previous study on protein separation with an aqueous two-phase solvent system using the nonsynchronous CCC apparatus. C1 Nihon Univ, Coll Pharm, Funabashi, Chiba 2748555, Japan. NHLBI, Lab Biophys Chem, 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.ac.jp NR 13 TC 6 Z9 6 U1 1 U2 2 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 2005 VL 28 IS 12-13 BP 1839 EP 1850 DI 10.1081/JLC/200063476 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 955ZZ UT WOS:000231270000005 ER PT J AU Wei, J Zhang, TY Ito, Y AF Wei, J Zhang, TY Ito, Y TI Preparative separation of tripdiolide from Chinese traditional herb by multidimensional CCC SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article; Proceedings Paper CT 3rd International Conference on Countercurrent Chromatography (CCC 2000) CY 2004 CL Tokyo, JAPAN DE multidimensional countercurrent chromatography; isolation and purification; tripdiolide; Tripterygium wilfordii Hook F ID CHROMATOGRAPHY; TRIPTERYGIUM AB Multidimensional countercurrent chromatography (CCC) was used for isolation and purification of tripdiolide from Tripterygium wilfordii Hook F. with a pair of two-phase solvent systems composed of n-hexane-dichloromethane-methanol-water (3:22:17:8, v/v/v/v) and chloroform-methanol-water (4:3:2, v/v/v), both of which were selected by analytical high-speed CCC. About 1 g of crude AA extract was separated using two preparative units of the HSCCC centrifuge, yielding 7.8 mg (0.78% w/w) of tripdiolide with a purity over 98%. C1 Beijing Inst New Technol Applicat, Beijing Res Ctr Separat & Purificat Technol Nat P, Beijing 100035, Peoples R China. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Wei, J (reprint author), Beijing Inst New Technol Applicat, Beijing Res Ctr Separat & Purificat Technol Nat P, Beijing 100035, Peoples R China. EM weijun0570@sina.com NR 8 TC 19 Z9 19 U1 1 U2 2 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 2005 VL 28 IS 12-13 BP 1903 EP 1911 DI 10.1081/JLC-200063550 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 955ZZ UT WOS:000231270000010 ER PT J AU Chadwick, LR Fong, HHS Farnsworth, NR Pauli, GF AF Chadwick, LR Fong, HHS Farnsworth, NR Pauli, GF TI CCC sample cutting for isolation of prenylated phenolics from hops SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article; Proceedings Paper CT 3rd International Conference on Countercurrent Chromatography (CCC 2000) CY 2004 CL Tokyo, JAPAN DE sample cutting; prenylated phenolics; isolation; CCC; hops ID HUMULUS-LUPULUS; CHROMATOGRAPHY; SEPARATION; SYSTEM; BEER AB One of the most potent estrogenic substances from the plant kingdom is the prenylated flavanone, 8-prenylnaringenin (8PN), present in hops (Humulus lupulus L., Cannabaceae) in low (< 10 ppm) concentrations. The prenylated chalcone desmethyl-xanthohumol (DMX), which is also present in this plant material, serves as a precursor to 8PN. A method for the preparative isolation of these and related bioactive phyto-chemicals has been developed that involves the use of multiple chromatographic techniques including complementary countercurrent chromatography (CCC) solvent systems. This paper describes the isolation of 8PN and DMX employing "sample-cutting CCC". The Hexanes-EtOAc-MeOH-H2O (HEMWat) solvent systems found to be effective for isolation of prenylated phenolics from hops range from HEMWat 8-2-8-2 for diprenylxanthohumol and 6,8-diprenylnaringenin, to HEMWat 6-4-6-4 for xanthohumol (XH), 6PN and 8PN, to HEMWat 5-5-5-5 for DMX, hydroxylated derivatives of XH, and humulinones. C1 Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy,Ctr Bot Dietry Supp, Program Collaborat Res Pharmaceut Sci,UIC,NIH, Chicago, IL 60612 USA. RP Pauli, GF (reprint author), Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy,Ctr Bot Dietry Supp, Program Collaborat Res Pharmaceut Sci,UIC,NIH, Chicago, IL 60612 USA. EM gfp@uic.edu OI Pauli, Guido/0000-0003-1022-4326 NR 13 TC 6 Z9 6 U1 0 U2 1 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 2005 VL 28 IS 12-13 BP 1959 EP 1969 DI 10.1081/JLC-200063634 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 955ZZ UT WOS:000231270000015 ER PT J AU Kurumatani, M Fujita, R Tagashira, M Shoji, T Kanda, T Ikeda, M Shoji, A Yanagida, A Shibusawa, Y Shindo, H Ito, Y AF Kurumatani, M Fujita, R Tagashira, M Shoji, T Kanda, T Ikeda, M Shoji, A Yanagida, A Shibusawa, Y Shindo, H Ito, Y TI Analysis of polyphenols from hop bract region using CCC SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article; Proceedings Paper CT 3rd International Conference on Countercurrent Chromatography (CCC 2000) CY 2004 CL Tokyo, JAPAN DE countercurrent chromatography; hop (Humulus lupulus L.); proanthocyanidin; glucosyltransferase ID PROANTHOCYANIDIN-RICH EXTRACT; MUTANS STREPTOCOCCI; APPLE PROCYANIDINS; GRAPE SEEDS; CHROMATOGRAPHY; POLYMERIZATION; SEPARATION AB Polyphenols derived from hop (Humulus lupulus L.) bract region (HBP) can be used as food materials, thereby preventing dental caries. Chemical details of the active substances need to be elucidated. The polyphenols from hop bract (HBP) region were purified by countercurrent chromatography (CCC). The fractions were analyzed by high-performance size-exclusion chromatography (HPSEC) and reversed phase high-performance liquid chromatography (RP-HPLC). From HBP fractions by HPSEC, some low-molecular- weight polyphenols (glycosides of flavonoids, catechins, and proanthocyanidins) were identified by RP-HPLC. However, a very hydrophilic fraction was found to have the most potent cavity-preventive activity, but it showed no peak in its RP-HPLC chromatogram (absence of small polyphenols). HPSEC analysis showed that the major components of this fraction were high-molecular weight substances, which were supposed to be proanthocyanidins, consisting of approximately 22 catechin units in its structure. C1 Asahi Brewery Co Ltd, Fundamental Res Lab, Ibaraki 3020106, Japan. Tokyo Univ Pharm & Life Sci, Sch Pharm, Div Struct Biol & Anal Sci, Tokyo, Japan. NHLBI, Biophys Chem Lab, Inst Hlth, Bethesda, MD USA. RP Tagashira, M (reprint author), Asahi Brewery Co Ltd, Fundamental Res Lab, 1-1-21 Midori, Ibaraki 3020106, Japan. EM motoyuki.tagashira@asahibeer.co.jp NR 18 TC 13 Z9 13 U1 1 U2 10 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 2005 VL 28 IS 12-13 BP 1971 EP 1983 DI 10.1081/JLC-200063640 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 955ZZ UT WOS:000231270000016 ER PT J AU Cao, XL Dong, YM Zhao, H Pan, X Ito, Y AF Cao, XL Dong, YM Zhao, H Pan, X Ito, Y TI Preparative separation of a minor active chromone from Aloe vera leaves by CCC SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article; Proceedings Paper CT 3rd International Conference on Countercurrent Chromatography (CCC 2000) CY 2004 CL Tokyo, JAPAN DE active chromone; Aloe vera; CCC; preparative separation ID GEL; BARBADENSIS AB HSCCC was applied successively in the preparative separation of a minor active chromone from an extract of Aloe vera leaves by combination with other traditional pretreatment, extraction, and partition methods. The chromone was finally identified as 8-C-beta-D-(2'-O-(E)-cinnamoyl) glycopyranosyl-2-(2-hydroxy) propyl-7-methoxy-5-methyl-chromone by FAB-MS, H-1 NMR, and C-13 NMR. Both of the solvent systems composed of the normal and reversed phase systems, such as CH2Cl2-MeOH-H2O (5:4:2, v/v/v) and hexane-ethyl acetate-methanol-water (1 :5 :1 :5, v/v/v/v), can be used for the preparative separation of the target chromone compound. The later solvent system was superior regarding sample loading capacity, environmental concerns (no chlorinated solvent), and peak resolution. C1 Beijing Technol & Business Univ, Sch Chem & Environm Engn, Beijing Key Lab Plant Resource Res & Dev, Beijing 100037, Peoples R China. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Cao, XL (reprint author), Beijing Technol & Business Univ, Sch Chem & Environm Engn, Beijing Key Lab Plant Resource Res & Dev, Beijing 100037, Peoples R China. EM caoxi@th.btbu.edu.cn NR 24 TC 11 Z9 11 U1 0 U2 0 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 2005 VL 28 IS 12-13 BP 2005 EP 2016 DI 10.1081/JLC-200063655 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 955ZZ UT WOS:000231270000019 ER PT J AU Ng, V Yu, H Ito, Y AF Ng, V Yu, H Ito, Y TI Preparative centrifugal precipitation chromatography using dialysis membrane inserted into convoluted tubing SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article; Proceedings Paper CT 3rd International Conference on Countercurrent Chromatography (CCC 2000) CY 2004 CL Tokyo, JAPAN DE centrifugal precipitation chromatography; preparative separation; protein purification and separation; ammonium sulfate gradient precipitation; dialysis tubing; convoluted tubing ID AMMONIUM-SULFATE; PROTEINS; FRACTIONATION AB The method uses preparative centrifugal precipitation chromatography comprising a seal-free continuous-flow centrifuge machine equipped with a plastic disk and a spiral groove which accommodates convoluted tubing. A dialysis membrane is inserted into the convoluted tubing to separate proteins according to their solubility in ammonium sulfate solution. The system relies on the original model of centrifugal precipitation chromatography, which employs the centrifugal force and a concentration gradient of precipitants to perform a repetitive process of precipitation and dissolution of protein molecules. Compared to the previous model, the current model results in a higher yield of separated compounds. C1 Univ Maryland, Baltimore, MD 21250 USA. Emory Univ, Atlanta, GA 30322 USA. NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD USA. RP Ng, V (reprint author), Univ Maryland, Baltimore, MD 21250 USA. EM vicng1@umbc.edu NR 4 TC 2 Z9 2 U1 0 U2 0 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 2005 VL 28 IS 12-13 BP 2061 EP 2070 DI 10.1081/JLC-200063675 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 955ZZ UT WOS:000231270000024 ER PT J AU Shiono, H Okada, T Ito, Y AF Shiono, H Okada, T Ito, Y TI Application of a novel continuous-flow cell separation method for separation of cultured human mast cells SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article; Proceedings Paper CT 3rd International Conference on Countercurrent Chromatography (CCC 2000) CY 2004 CL Tokyo, JAPAN DE continuous flow cell; human mast cells AB A novel, continuous cell separation method, based on density differences, is developed for application to transfusion medicine. Performance of a miniature separation column with ca. 8 mL capacity was examined on separation of human huffy coat (containing 10(7) nucleated cells and 10(10) erythrocytes/mL). Differential leukocyte counts revealed that lymphocytes were concentrated in two fractions of density 1.065 to 1.070. Neutrophils were located in another fraction (density 1.080), while some cells present in early eluted low density fractions were difficult to identify by microscope examination. Flow cytometry analysis revealed that CD34-positive cells, which are considered to be stem cells, were relatively concentrated in an early eluted fraction. Comparing the data obtained from hemocytometer and flow cytometry suggested the presence of immature CD45-negative nucleated cells in the same fraction. These results indicate that the present density method might be capable of collecting CD34-negative stem cells from peripheral blood. The present method was applied to the separation of cultured human mast cells. When the co-cultured cell suspension containing 3.5 x 10(6) cells (approximately 10% of mast cells and 90% of fibroblasts) was separated with a set of media (density: 1.065-1.085); fibroblasts were concentrated in a fraction of density 1.065 with a few young mast cells. Densely granulated matured mast cells were collected in a fraction of density 1.085. The method could also be used to detect minute changes in cell density under various physiological and pathological conditions. C1 Aichi Med Univ, Sch Med, Dept Physiol, Nagakute, Aichi 48011, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Okada, T (reprint author), Aichi Med Univ, Sch Med, Dept Physiol, Nagakute, Aichi 48011, Japan. NR 7 TC 5 Z9 5 U1 0 U2 0 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 2005 VL 28 IS 12-13 BP 2071 EP 2083 DI 10.1081/JLC-200063678 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 955ZZ UT WOS:000231270000025 ER PT J AU Gosse, B Amissa, AA Adje, FA Niamke, FB Ollivier, D Ito, Y AF Gosse, B Amissa, AA Adje, FA Niamke, FB Ollivier, D Ito, Y TI Analysis of components of Neem (Azadirachta indica) oil by diverse chromatographic techniques SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE Neem; Azadirachta indica ID VIRGIN OLIVE OIL; PHENOLIC-COMPOUNDS AB The seed of Neem Azadirachta indica (Meliaceae) was analyzed by various chromatographic methods."' The hexane extract yielded six fatty acids and six unsaponified compounds resolved by high speed countercurrent chromatography (HSCCC) and confirmed by GC. These compounds are the main constituents of the solid substance of the hexane extract of the seed used in traditional medicine since ancient times. In 1968 Butterworth and Morgan isolated azadirachfin as the main insecticidal component of Neem. ([2]) To date, more than 300 natural products have been isolated from different parts of the tree, with new compounds added to the list every year. 133 Here, we report the isolation and chemical analysis of the hexane extract whole components. C1 NHLBI, NIH, Bethesda, MD 20892 USA. Inst Natl Polytech, Dept Chim, Lab Substances Nat Bioactives, Yamoussoukro, Cote Ivoire. Lab Interreg Repress Fraudes, Marseille, France. RP Ito, Y (reprint author), NHLBI, NIH, Bldg 50,Room 3334,50 South Dr, Bethesda, MD 20892 USA. EM itoy2@mail.nih.gov NR 12 TC 9 Z9 9 U1 1 U2 6 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 2005 VL 28 IS 14 BP 2225 EP 2233 DI 10.1081/JLC-200064164 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 960SU UT WOS:000231614300007 ER PT J AU Ikehata, JI Shinomiya, K AF Ikehata, JI Shinomiya, K TI Partition efficiencies of an eccentric coiled separation column for centrifugal partition chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE centrifugal partition chromatography; efficiency; eccentric coiled column ID COUNTER-CURRENT CHROMATOGRAPHY; PLANET CENTRIFUGE; CORIOLIS-FORCE AB The partition efficiency of an eccentric coiled separation column, newly fabricated in our laboratory, was studied using centrifugal partition chromatography (CPC) with four different two-phase solvent systems including n-hexane-acetonitrile; tert-butyl methyl ether-aqueous 0.1% trifluoroacetic acid (I : 1); 1-butanol-water (I : 1); and 12.5% (w/w) polyethylene glycol 1000-12.5% (w/w) dibasic potassium phosphate. Each separation was performed by eluting either the upper phase in the ascending mode or the lower phase in the descending mode, each in clockwise and counterclockwise (CCW) column rotation. Better partition efficiencies were attained by the CCW rotation in both mobile phases in all the two-phase solvent systems examined. The overall results demonstrated that the coiled separation column yielded substantially higher partition efficiencies than the commercial disk column. The eccentric coiled separation column is useful for the separation by CPC. C1 Nihon Univ, Coll Pharm, Funabashi, Chiba 2748555, Japan. NHLBI, Ctr Biochem & Biophys, 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.ac.jp NR 9 TC 2 Z9 2 U1 0 U2 1 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 2005 VL 28 IS 17 BP 2807 EP 2818 DI 10.1080/10826070500225275 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 981HV UT WOS:000233079500011 ER PT J AU Shibusawa, Y Shoji, A Yanagida, A Shindo, H AF Shibusawa, Y Shoji, A Yanagida, A Shindo, H TI Determination of log P-o/w for catechins and their isomers, oligomers, and other organic compounds by stationary phase controlled high speed countercurrent chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE high speed countercurrent chromatography (HSCCC); stationary phase volume; stationary phase fraction (S-F) controlled HSCCC; log P-o/w value; catechins ID CENTRIFUGAL PARTITION CHROMATOGRAPHY; COEFFICIENTS; OCTANOL; WATER AB A new technique, stationary phase volume controlled high speed countercurrent chromatography (HSCCC), was used to determine the octanol-water partition coefficients (P-o/w) of catechins and their isomers, oligomers, and other organic compounds. The stationary phase volume in the CCC column was effectively controlled under hydrodynamic equilibrium system. The log P-o/w values ranging from -1.35 to +3.60 were measured within 21 min using this new HSCCC technology. The linear relationship (correlation coefficient value, r = 0.993) was observed between log P-o/w values obtained by the shake-flask method and those values by the HSCCC method. In this technique, it is possible to inject multiple samples successively into the CCC column at short intervals to measure their retention times without renewing the stationary phase volume. C1 Tokyo Univ Pharm & Life Sci, Div Struct Biol & Analyt Sci, Hachioji, Tokyo 1920392, Japan. Asahi Brewery Co Ltd, Fundamental Res Lab, Ibaraki, Japan. NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD USA. RP Shibusawa, Y (reprint author), Tokyo Univ Pharm & Life Sci, Div Struct Biol & Analyt Sci, 1432-1 Horinouchi, Hachioji, Tokyo 1920392, Japan. EM sibusawa@ps.toyaku.ac.jp NR 20 TC 15 Z9 15 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 2005 VL 28 IS 17 BP 2819 EP 2834 DI 10.1080/10826070500225317 PG 16 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 981HV UT WOS:000233079500012 ER PT J AU Geissler, E Hecht, AM Horkay, F AF Geissler, E Hecht, AM Horkay, F TI Nanoscale inhomogeneities and thermodynamics of unfilled polymer gels SO JOURNAL OF MACROMOLECULAR SCIENCE-PHYSICS LA English DT Article DE SANS; inhomogeneities; polymer gels; osmotic modulus ID SCATTERING; SWOLLEN AB The description of the structure of swollen polymer networks and its relationship with mechanical and thermodynamic properties has been an unresolved problem for a long time. In spite of a number of theoretical approaches, no simple formalism has been found that captures the structural variety of real gels. Here we report a new approach to describe inhomogeneities in the nanometer size range that develop in the course of the cross-linking process, and their relationship with the macroscopic elastic properties. Experimental data from small angle neutron scattering (SANS), osmotic swelling pressure, and elastic modulus measurements were obtained on polyfluorosilicone (PFSi) gels prepared by different cross-linking processes from precursor chains of monomodal and bimodal distributions. The neutron scattering response of these gels reveals two types of concentration fluctuations, namely, those originating from nanoscale frozen-in constraints generated by the cross-links and the time-dependent thermodynamic fluctuations associated with the osmotic properties of the network chains. The amplitude of the frozen-in concentration fluctuations deduced from small angle neutron scattering measurements is found to be proportional to the ratio of the macroscopic elastic shear modulus to the osmotic compression modulus. The thermodynamic concentration fluctuations are in agreement with the results of dynamic light scattering and macroscopic osmotic pressure measurements. The present approach describes the effect of the nanoscale features on the macroscopic properties of the gel. C1 Univ Grenoble 1, CNRS, UMR 5588, Spectrometrie Phys Lab, F-38402 St Martin Dheres, France. NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD USA. RP Geissler, E (reprint author), Univ Grenoble 1, CNRS, UMR 5588, Spectrometrie Phys Lab, BP 87, F-38402 St Martin Dheres, France. EM erik.geissler@ujf-grenoble.fr NR 14 TC 3 Z9 3 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0022-2348 J9 J MACROMOL SCI PHYS JI J. Macromol. Sci.-Phys. PY 2005 VL B44 IS 6 BP 873 EP 880 DI 10.1080/00222340500323615 PG 8 WC Polymer Science SC Polymer Science GA 997KT UT WOS:000234244900007 ER PT J AU Choi, IY Lee, SP Shen, J AF Choi, IY Lee, SP Shen, J TI In vivo single-shot three-dimensionally localized multiple quantum spectroscopy of GABA in the human brain with improved spectral selectivity SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE MRS; localization; GABA; human brain in vivo; homocarnosine ID GAMMA-AMINOBUTYRIC-ACID; COHERENCE TRANSFER; FILTER; SUPPRESSION; EXCITATION; RESONANCES; LACTATE; PULSES; NMR AB A single-shot multiple quantum filtering method is developed that uses two doubie-band frequency selective pulses enhanced spectral selectivity in combination with a slice-selective 90degrees, a slice-selective universal rotator 90degrees, and a spectral-spatial pulse composed of two slice-selective universal rotator 45degrees pulses for single-shot three-dimensional localization. The use of ibis selective multiple quantum filtering method for C-3 and C-4 methylene protons of GABA resulted in improved spectral selectivity for GABA and effective suppression of overlapping signals Such as creatine and glutathione in each single scan, providing reliable measurement of the GABA doublet in all subjects. The concentration of GABA was measured to be 0.7 +/- 0.2 mumol/g (means +/- SD, n = 15) in the fronto-parietal region of the human brain in vivo. (C) 2004 Elsevier Inc. All rights reserved. C1 Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. NIMH, NIH, Bethesda, MD 20892 USA. RP Choi, IY (reprint author), Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. EM iychoi@nki.rfmh.org OI Lee, Phil/0000-0002-2087-8887 FU NIA NIH HHS [R03AG022193]; NIBIB NIH HHS [8R01EB00315] NR 25 TC 12 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD JAN PY 2005 VL 172 IS 1 BP 9 EP 16 DI 10.1016/j.jmr.2004.09.021 PG 8 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 885SI UT WOS:000226176800002 PM 15589402 ER PT J AU Wasserman, BA Casal, SG Astor, BC Aletras, AH Arai, AE AF Wasserman, BA Casal, SG Astor, BC Aletras, AH Arai, AE TI Wash-in kinetics for gadolinium-enhanced magnetic resonance imaging of carotid atheroma SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE arteriosclerosis; magnetic resonance; vascular studies; carotid arteries; stenosis or obstruction; contrast agents; gadolinium ID ATHEROSCLEROTIC PLAQUE; FIBROUS CAP; EX-VIVO; MRI; ARTERIES; COMPONENTS; MORPHOLOGY; ACCURACY; CONTRAST; IMAGES AB Purpose: To determine the wash-in kinetics of intravenous gadolinium into the fibrous cap and lipid core of carotid atheroma, and identify the time following gadolinium administration that maximizes contrast between the cap and core. Materials and Methods: Seven subjects with carotid artery stenosis were studied. Magnetic resonance (MR) images of the atheroma were acquired using a single-inversion-recovery fast-spin-echo (IR FSE) sequence, which was serially repeated during the first 30 minutes following intravenous gadolinium administration. Postcontrast time was divided into three intervals: < 10, 11-20, and > 21 minutes. Adjusted signal intensity (SI), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) values for postcontrast images were compared to adjusted precontrast values. Results: The mean SNRs of the cap and core were significantly elevated in each postcontrast interval compared with mean precontrast values. The CNRs of the cap vs. the core increased by 19.8% (3.03 to 4.14, P = 0.03) in the first 10 minutes following gadolinium administration, and remained elevated over the next two intervals with a slight decrease in the final interval. Conclusion: Increased signal and contrast between the cap and core can be achieved by imaging up to 30 minutes following gadolinium administration, with peak enhancement occurring in the first 10 minutes. C1 Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Wasserman, BA (reprint author), Johns Hopkins Univ Hosp, Dept Radiol, Phipps B-100,600 N Wolfe St, Baltimore, MD 21287 USA. EM bwasser@jhmi.edu OI Aletras, Anthony/0000-0002-3786-3817 NR 22 TC 25 Z9 25 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JAN PY 2005 VL 21 IS 1 BP 91 EP 95 DI 10.1002/jmri.20228 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 884MV UT WOS:000226090400014 PM 15611945 ER PT J AU Clarke, R Smith, G AF Clarke, R Smith, G TI Stem cells and tissue homeostasis in mammary glands SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Editorial Material ID TEMPLATE DNA STRANDS; SELF-RENEWAL; SEGREGATION; CANCER C1 Univ Manchester, Breast Biol Grp, Christie Hosp NHS Trust, Manchester M20 4BX, Lancs, England. NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Clarke, R (reprint author), Univ Manchester, Breast Biol Grp, Christie Hosp NHS Trust, Manchester M20 4BX, Lancs, England. EM rclarke@picr.man.ac.uk OI Clarke, Robert/0000-0001-5407-3123 NR 11 TC 7 Z9 8 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS 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 2005 VL 10 IS 1 BP 1 EP 3 DI 10.1007/s10911-005-2535-4 PG 3 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 924ZR UT WOS:000229021800001 PM 15886881 ER PT J AU Wagner, KU Smith, GH AF Wagner, KU Smith, GH TI Pregnancy and stem cell behavior SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE mammary gland; differentiation; parity-induced mammary epithelial cells; stem cells; Cre recombinase; tumorigenesis; ErbB2; MMTV ID MAMMARY EPITHELIAL-CELLS; BREAST-CANCER; FUNCTIONAL-DIFFERENTIATION; TGF-BETA-1 EXPRESSION; PROGENITOR CELLS; DNA-SYNTHESIS; SELF-RENEWAL; CYCLE ARREST; GLAND; MICE AB The identification of cancer-initiating epithelial subtypes (i.e. cancer stem cells) is important for gaining a more comprehensive understanding of the process of neoplastic transformation and tumorigenesis. Since reproductive history has a major impact on breast tumorigenesis, it is reasonable to assume that pregnancy and lactation have enduring effects on the cancer susceptibility of multipotent progenitors. Using the Cre-lox technology as a tool to genetically label pregnancy-hormone-responsive cells, we identified a mammary epithelial subtype that is abundant in parous females. These pregnancy-induced mammary epithelial cells (PI-MECs) originate from differentiating cells during the first pregnancy and lactation cycle. They do not undergo apoptosis during postlactational remodeling, and they persist throughout the remainder of a females life. In this review, we discuss the biological relevance of PI-MECs in multiparous females and their important stem cell-like features, such as self renewal, as well as their ability to produce progeny with diverse cellular fates. Using appropriate animal models, we further demonstrate that PI-MECs are cellular targets for pregnancy-enhanced mammary tumorigenesis. C1 Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Wagner, KU (reprint author), Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, 986805 Nebraska Med Ctr,Rm 8009, Omaha, NE 68198 USA. EM kuwagner@unmc.edu RI Wagner, Kay-Uwe/B-6044-2009 FU NCI NIH HHS [CA93797] NR 64 TC 36 Z9 37 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS 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 2005 VL 10 IS 1 BP 25 EP 36 DI 10.1007/s10911-005-2538-1 PG 12 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 924ZR UT WOS:000229021800004 PM 15886884 ER PT J AU Murphy, CM Huestis, MA AF Murphy, CM Huestis, MA TI Liquid chromatographic/electrospray ionization tandem mass spectrometric analysis for the quantification of buprenorphine, norbuprenorphine, buprenorphine-3-beta-D-glucuronide and norbuprenorphine-3-beta-D-glucuronide in human plasma SO JOURNAL OF MASS SPECTROMETRY LA English DT Article DE buprenorphine; norbuprenorphine; glucuronide; electrospray ionization; tandem mass spectrometry ID METABOLISM; NALOXONE AB A liquid chromatographic/electrospray ionization tandem mass spectrometric method for the quantification of the synthetic opiate buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine-3-beta-D-glucuronide (BUP-3-G) and norbuprenorphine-3-beta-D-glucuronide (NBUP-3-G) in human plasma was developed and validated. Identification and quantification were based on the following transitions: m/z 468 to 396 and 414 for BUP, m/z 414 to 326 and 340 for NBUP, m/z 644 to 468 for BUP-3-G and m/z 590 to 414 for NBUP-3-G. Calibration by linear regression analysis utilized deuteratated internal standards and a weighting factor of 1/x. The method was accurate and precise across a linear dynamic range of 0.6-50.0 ng ml(-1). Pretreatment of plasma samples using solid-phase extraction was sufficient to limit matrix suppression to <30% for all four analytes. The method proved to be suitable for the quantification of BUP and the related metabolites in plasma samples collected from BUP-maintained study participants. Copyright (C) 2004 John Wiley Sons, Ltd. C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov NR 9 TC 33 Z9 34 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD JAN PY 2005 VL 40 IS 1 BP 70 EP 74 DI 10.1002/jms.776 PG 5 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA 895OK UT WOS:000226872500010 PM 15637731 ER PT J AU Chaiworapongsa, T Romero, R Kim, YM Kim, GJ Kim, MR Espinoza, J Bujold, E Goncalves, L Gomez, R Edwin, S Mazor, M AF Chaiworapongsa, T Romero, R Kim, YM Kim, GJ Kim, MR Espinoza, J Bujold, E Goncalves, L Gomez, R Edwin, S Mazor, M TI Plasma soluble vascular endothelial growth factor receptor-1 concentration is elevated prior to the clinical diagnosis of pre-eclampsia SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE pre-eclampsia; plasma-soluble vascular endothelial growth factor 1; longitudinal study; early onset; late onset; VEGF; PIGF ID UTERINE ARTERY DOPPLER; VELOCITY WAVE-FORMS; HUMAN EXTRAVILLOUS TROPHOBLAST; PLACENTAL VILLOUS TREE; BED SPIRAL ARTERIES; FETAL-GROWTH; FLOW VELOCITY; NITRIC-OXIDE; HUMAN CYTOTROPHOBLASTS; UMBILICAL ARTERY AB Objective: Accumulating evidence suggests that the balance between vascular endothelial growth factor ( VEGF), placental growth factor ( PlGF), and their receptors is important for effective vasculogenesis, angiogenesis, and placental development. Recently, the soluble form of VEGFR-1 (sVEGFR-1), an antagonist to VEGF and PlGF, has been implicated in the pathophysiology of pre-eclampsia. Plasma sVEGFR-1 concentration is elevated in pre-eclampsia at the time of clinical diagnosis and correlates with the severity of the disease. The purpose of this study was to determine whether the concentrations of sVEGFR-1 in plasma of pre-eclamptic patients change prior to the clinical manifestations of the disease. Methods: A longitudinal case-control study was conducted in normal pregnant women ( n=44) and patients with preeclampsia ( n = 44). Blood sampling was performed at six intervals: ( 1) 7 - 16 weeks; ( 2) 16 - 24 weeks; ( 3) 24 - 28 weeks; ( 4) 28 - 32 weeks; ( 5) 32 - 36 weeks; and ( 6) more than 37 weeks of gestation. To examine the relationship between plasma sVEGFR-1 concentration and interval to clinical diagnosis of pre-eclampsia, plasma samples of pre-eclamptic patients at different gestational ages were stratified according to the interval from blood sampling to clinical development of the disease into five groups: ( 1) at clinical manifestation; ( 2) 2 - 5 weeks; ( 3) 6 - 10 weeks; ( 4) 11 - 16 weeks; and ( 5) 17 - 25 weeks before clinical manifestations. Plasma concentrations of sVEGFR-1 were determined by enzyme-linked immunoassay. Parametric statistics and repeated measure procedures were used for the analysis. Results: The mean plasma sVEGFR-1 concentration in pre-eclamptic patients before the clinical manifestation of the disease was significantly higher than in normal pregnant women at 24 - 28, 28 - 32, and 32 - 37 weeks of gestation ( p = 0.02, p<0.001, and p<0.001, respectively). In contrast, no significant differences in the mean plasma sVEGFR-1 concentration between patients with pre-eclampsia and normal pregnant women were observed both at 7 - 16 weeks and 16 - 24 weeks of gestation ( p= 0.1 and p = 0.9). Similarly, the mean plasma sVEGFR-1 concentration was significantly higher in pre-eclamptic patients than in normal pregnant women at clinical manifestation, at 2 - 5 weeks ( mean 3.8 weeks), and at 6 - 10 weeks ( mean 8.2 weeks) prior to the development of clinical pre-eclampsia ( p<0.001, p<0.001, and p = 0.002, respectively). Among patients with early-onset pre-eclampsia ( defined as gestational age of 34 weeks or less), the mean plasma sVEGFR-1 concentration was significantly higher in pre-eclampsia ( before clinical diagnosis) than in normal pregnant women at 24 - 28 ( mean 26.4) weeks of gestation ( p = 0.008). In contrast, among patients with the late-onset disease ( defined as gestational age of more than 34 weeks), plasma sVEGFR-1 concentration in pre-clinical pre-eclampsia was significantly higher than in normal pregnant women at 28 - 32 ( mean 30.2) weeks of gestation ( p<0.001). Conclusions: Plasma sVEGFR-1 concentration is elevated in pre-eclampsia prior to the clinical diagnosis of the disease. This elevation began 6 - 10 weeks prior to the clinical manifestations, and the increase was more pronounced at 2 - 5 weeks before the diagnosis, as well as at clinical presentation. Furthermore, in early-onset pre-eclampsia, plasma concentration of sVEGFR-1 is elevated earlier than the late-onset disease. C1 Wayne State Univ, Dept Obstet & Gynecol, NICHD, Sch Med,Perinatol Res Branch,Hutzel Women Hosp 3, Detroit, MI 48201 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. Wayne State Univ, Dept Pathol, Sch Med, Detroit, MI 48202 USA. Sotero del Rio Hosp, CEDIP, Dept Obstet & Gynecol, Puente Alto, Chile. Ben Gurion Univ Negev, Dept Obstet & Gynecol, Soroka Med Ctr, Beer Sheva, Israel. RP Romero, R (reprint author), Wayne State Univ, Dept Obstet & Gynecol, NICHD, Sch Med,Perinatol Res Branch,Hutzel Women Hosp 3, 3990, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov NR 139 TC 193 Z9 205 U1 0 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD JAN PY 2005 VL 17 IS 1 BP 3 EP 18 DI 10.1080/14767050400028816 PG 16 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 933ZU UT WOS:000229672500002 PM 15804781 ER PT J AU Hurst, SA Hull, SC DuVal, G Danis, M AF Hurst, SA Hull, SC DuVal, G Danis, M TI How physicians face ethical difficulties: a qualitative analysis SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID CONSULTATION SERVICE; MEDICAL-STUDENTS; CARE; DILEMMAS AB Background: Physicians face ethical difficulties daily, yet they seek ethics consultation infrequently. To date, no systematic data have been collected on the strategies they use to resolve such difficulties when they do so without the help of ethics consultation. Thus, our understanding of ethical decision making in day to day medical practice is poor. We report findings from the qualitative analysis of 310 ethically difficult situations described to us by physicians who encountered them in their practice. When facing such situations, the physicians sought to avoid conflict, obtain assistance, and protect the integrity of their conscience and reputation, as well as the integrity of the group of people who participated in the decisions. These goals could conflict with each other, or with ethical goals, in problematic ways. Being aware of these potentially conflicting goals may help physicians to resolve ethical difficulties more effectively. This awareness should also contribute to informing the practice of ethics consultation. Objective: To identify strategies used by physicians in dealing with ethical difficulties in their practice. Design, setting, and participants: National survey of internists, oncologists, and intensive care specialists by computer assisted telephone interviews ( n = 344, response rate = 64%). As part of this survey, we asked physicians to tell us about a recent ethical dilemma they had encountered in their medical practice. Transcripts of their open-ended responses were analysed using coding and analytical elements of the grounded theory approach. Main measurements: Strategies and approaches reported by respondents as part of their account of a recent ethical difficulty they had encountered in their practice. Results: When faced with ethical difficulties, the physicians avoided conflict and looked for assistance, which contributed to protecting, or attempting to protect, the integrity of their conscience and reputation, as well as the integrity of the group of people who participated in the decisions. These efforts sometimes reinforced ethical goals, such as following patients' wishes or their best interests, but they sometimes competed with them. The goals of avoiding conflict, obtaining assistance, and protecting the respondent's integrity and that of the group of decision makers could also compete with each other. Conclusion: In resolving ethical difficulties in medical practice, internists entertained competing goals that they did not always successfully achieve. Additionally, the means employed were not always the most likely to achieve those aims. Understanding these aspects of ethical decision making in medical practice is important both for physicians themselves as they struggle with ethical difficulties and for the ethics consultants who wish to help them in this process. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Univ Toronto, Joint Ctr Bioeth, Toronto, ON, Canada. RP Hurst, SA (reprint author), Bioeth Res & Teaching Unit, Villa Thury 8-CMU,Rue Michel Serv 1, CH-1211 Geneva 4, Switzerland. EM samia.hurst@medecine.unige.ch RI Hurst, Samia/A-9661-2008 OI Hurst, Samia/0000-0002-1980-5226 NR 33 TC 45 Z9 45 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD JAN 1 PY 2005 VL 31 IS 1 BP 7 EP 14 DI 10.1136/jme.2003.005835 PG 8 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 885BG UT WOS:000226130400003 PM 15634746 ER PT J AU Resnik, DB AF Resnik, DB TI Eliminating the daily life risks standard from the definition of minimal risk SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID CHILDREN AB The phrase "minimal risk,'' as defined in the United States' federal research regulations, is ambiguous and poorly defined. This article argues that most of the ambiguity that one finds in the phrase stems from the "daily life risks'' standard in the definition of minimal risk. In this article, the author argues that the daily life risks standard should be dropped and that "minimal risk'' should be defined as simply "the probability and magnitude of the harm or discomfort anticipated in research are not greater than those encountered during the performance of routine physical or psychological examinations or tests''. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Box 12233,NH06, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov NR 17 TC 29 Z9 29 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD JAN 1 PY 2005 VL 31 IS 1 BP 35 EP 38 DI 10.1136/jme.2004.010470 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 885BG UT WOS:000226130400008 PM 15634751 ER PT J AU Lin, JP O'Donnell, CJ Levy, D Cupples, LA AF Lin, JP O'Donnell, CJ Levy, D Cupples, LA TI Evidence for a gene influencing haematocrit on chromosome 6q23-24: genomewide scan in the Framingham Heart Study SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID FETAL-HEMOGLOBIN PRODUCTION; SOMATIC-CELL HYBRIDS; INTERMITTENT CLAUDICATION; CEREBRAL INFARCTION; LINKAGE ANALYSIS; BLOOD-VISCOSITY; RISK; DISEASE; LOCALIZATION; CLONING C1 NHLBI, DECA, NIH, Bethesda, MD 20892 USA. NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Boston Univ, Sch Med, Div Cardiol, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. RP Lin, JP (reprint author), NHLBI, DECA, NIH, 6701 Rockledge Dr,Suite 8110, Bethesda, MD 20892 USA. EM linj@nhlbi.nih.gov FU NHLBI NIH HHS [N01-HC-25195] NR 38 TC 15 Z9 15 U1 0 U2 0 PU B M J PUBLISHING 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 2005 VL 42 IS 1 BP 75 EP 79 DI 10.1136/jmg.2004.021097 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 890KL UT WOS:000226510000012 PM 15635079 ER PT J AU Grama, LM Beckwith, M Bittinger, W Blais, D Lollar, C Middleswarth, A Noone, M Price, D Quint-Kasner, S Shields, V Wright, LW AF Grama, LM Beckwith, M Bittinger, W Blais, D Lollar, C Middleswarth, A Noone, M Price, D Quint-Kasner, S Shields, V Wright, LW TI The role of user input in shaping online information from the National Cancer Institute SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE cancer information; Internet; online information; usability; website AB The National Cancer Institute (NCI) was among the first federal agencies to recognize the potential of the Internet for disseminating health-related information. The evolution and refinement of NCI's online cancer information has been substantially "user driven"-from the launch of CancerNet in 1995 to the recent redesign of its award-winning successor, the NCI website. This article presents an overview of NCI's multi-pronged approach to gathering input about its online information products, including stakeholder meetings, focus groups, standard and customized online user surveys, usability testing, heuristic reviews, and search log analysis. Also highlighted are some of the many enhancements that have been made to NCI's online cancer information products based on user input. C1 NCI, Off Canc Informat Prod & Syst, Off Commun, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. RP Grama, LM (reprint author), 6116 Execut Blvd,Rm 3121, Rockville, MD 20852 USA. EM lgrama@mail.nih.gov NR 15 TC 2 Z9 2 U1 0 U2 2 PU JOURNAL OF MEDICAL INTERNET RESEARCH PI TORONTO PA TORONTO GENERAL HOSPITAL, R FRASER ELLIOTT BLDG, 4TH FL, R 4S435, 190 ELIZABETH ST, TORONTO, ON M5G 2C4, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PY 2005 VL 7 IS 3 DI 10.2196/jmir.7.3.e25 PG 13 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 970JS UT WOS:000232304600014 ER PT J AU Wood, FB Benson, D LaCroix, EM Siegel, ER Fariss, S AF Wood, FB Benson, D LaCroix, EM Siegel, ER Fariss, S TI Use of Internet audience measurement data to gauge market share for online health information services SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE Internet; World Wide Web; information services; information dissemination; audience research; evaluation studies AB Background: The transition to a largely Internet and Web-based environment for dissemination of health information has changed the health information landscape and the framework for evaluation of such activities. A multidimensional evaluative approach is needed. Objective: This paper discusses one important dimension of Web evaluation-usage data. In particular, we discuss the collection and analysis of external data on website usage in order to develop a better understanding of the health information (and related US government information) market space, and to estimate the market share or relative levels of usage for National Library of Medicine (NLM) and National Institutes of Health (NIH) websites compared to other health information providers. Methods: The primary method presented is Internet audience measurement based on Web usage by external panels of users and assembled by private vendors-in this case, comScore. A secondary method discussed is Web usage based on Web log software data. The principle metrics for both methods are unique visitors and total pages downloaded per month. Results: NLM websites (primarily MedlinePlus and PubMed) account for 55% to 80% of total NIH website usage depending on the metric used. In turn, NIH.gov top-level domain usage (inclusive of NLM) ranks second only behind WebMD in the US domestic home health information market and ranks first on a global basis. NIH.gov consistently ranks among the top three or four US government top-level domains based on global Web usage. On a site-specific basis, the top health information websites in terms of global usage appear to be WebMD, MSN Health, PubMed, Yahoo! Health, AOL Health, and MedlinePlus. Based on MedlinePlus Web log data and external Internet audience measurement data, the three most heavily used cancer-centric websites appear to be www.cancer.gov (National Cancer Institute), www.cancer.org (American Cancer Society), and www.breastcancer.org (non-profit organization). Conclusions: Internet audience measurement has proven useful to NLM, with significant advantages compared to sole reliance on usage data from Web log software. Internet audience data has helped NLM better understand the relative usage of NLM and NIH websites in the intersection of the health information and US government information market sectors, which is the primary market intersector for NLM and NIH. However important, Web usage is only one dimension of a complete Web evaluation framework, and other primary research methods, such as online user surveys, usability tests, and focus groups, are also important for comprehensive evaluation that includes qualitative elements, such as user satisfaction and user friendliness, as well as quantitative indicators of website usage. C1 Natl Lib Med, Off Hlth Informat Programs Dev, NIH, Bethesda, MD 20894 USA. RP Wood, FB (reprint author), Natl Lib Med, Off Hlth Informat Programs Dev, NIH, 8600 Rockville Pike,Bldg 38,Rm 2S14, Bethesda, MD 20894 USA. EM fredwood@mail.nih.gov NR 3 TC 1 Z9 1 U1 3 U2 11 PU JOURNAL OF MEDICAL INTERNET RESEARCH PI TORONTO PA TORONTO GENERAL HOSPITAL, R FRASER ELLIOTT BLDG, 4TH FL, R 4S435, 190 ELIZABETH ST, TORONTO, ON M5G 2C4, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PY 2005 VL 7 IS 3 DI 10.2196/jmir.7.3.e31 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 970JS UT WOS:000232304600005 ER PT J AU Smith-Bindman, R Ballard-Barbash, R Miglioretti, DL Patnick, J Kerlikowske, K AF Smith-Bindman, R Ballard-Barbash, R Miglioretti, DL Patnick, J Kerlikowske, K TI Comparing the performance of mammography screening in the USA and the UK SO JOURNAL OF MEDICAL SCREENING LA English DT Article ID BREAST-CANCER; DIAGNOSTIC MAMMOGRAPHY; UNITED-KINGDOM; MEDICAL AUDIT; 22 COUNTRIES; FOLLOW-UP; PROGRAM; WOMEN; ACCURACY; OUTCOMES AB To compare the performance of screening mammography in the USA and the UK, a consecutive sample of screening mammograms was obtained in women aged 50 and older from 1996 to 1999 who participated in the Breast Cancer Surveillance Consortium in the USA (n = 978,591) and the National Health Service Breast Cancer Screening Program in the UK (n = 3.94 million), including 6943 diagnosed with breast cancer within 12 months of screening. Recall rates were defined as the percentage of screening mammograms with a recommendation for further evaluation including diagnostic mammography, ultrasound, clinical examination or biopsy, and cancer detection rates including invasive cancer and ductal carcinoma in situ diagnosed within 12 months of a screening mammogram. All results were stratified by whether examinations were first or Subsequent and adjusted to a standard age distribution. Among women Who underwent a first screening mammogram, 13.3% of women in the USA versus 7.2% of women in the UK were recalled for further evaluation (relative risk for recall 1.9; 95% CI 1.8-1.9). For subsequent examinations recall rates were approximately 50% lower, but remained twice as high in the USA as in the UK. A similar percentage of wornen underwent biopsy in each setting, but rates of percutaneous biopsy were lower and rates of open surgical biopsy were higher in the USA. Women undergo screening approximately every 18 months in the USA and every 36 months in the UK. Based on a 20-year period of screening, the estimated percentage of women who would be recalled for additional testing was nearly threefold higher in the USA. The number of cancers detected was also higher in the USA (55 versus 43), and most of the increase was in the detection of small invasive and in situ cancers. The numbers of large cancers detected (> 2 cm) were very similar between the two countries. Recall rates are approximately two to three times higher in the USA than in the UK. importantly, despite less frequent screening in the USA, there are no Substantial differences in the rates of detection of large cancers. Efforts to improve mammographic screening in the USA Should target lowering the recall rate without reducing the cancer detection rate. C1 Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94115 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94115 USA. NCI, Appl Res Program, NIH, Bethesda, MD 20892 USA. Univ Washington, Ctr Hlth Studies, Grp Hlth Cooperat, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Natl Hlth Serv Breast Screening Programs, Sheffield, S Yorkshire, England. Univ Calif San Francisco, Dept Med, San Francisco, CA 94115 USA. Univ Calif San Francisco, Gen Internal Med Sect, Dept Vet Affairs, San Francisco, CA 94115 USA. RP Smith-Bindman, R (reprint author), Univ Calif San Francisco, Dept Radiol, Mt Zion Campus,1600 Divisadero St,Box 1667, San Francisco, CA 94115 USA. EM Rebecca.Smith-Bindman@Radiology.UCSF.edu FU NCI NIH HHS [UO1CA69976, CA86032, UO1CA63736, UO1CA86082, UO1CA86076, UO1CA70040, UO1CA63731, UO1CA63740, UO1CA70013] NR 32 TC 46 Z9 46 U1 0 U2 4 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0969-1413 J9 J MED SCREEN JI J. Med. Screen. PY 2005 VL 12 IS 1 BP 50 EP 54 DI 10.1258/0969141053279130 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 028WD UT WOS:000236518600010 PM 15814020 ER PT J AU Lamb, PW Melton, MA Yakel, JL AF Lamb, PW Melton, MA Yakel, JL TI Inhibition of neuronal nicotinic acetylcholine receptor channels expressed in Xenopus oocytes by beta-amyloid(1-42) peptide SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE hippocampus; electrophysiology; Alzheimer's disease; plasticity; patch clamp ID RAT HIPPOCAMPAL SLICES; CENTRAL-NERVOUS-SYSTEM; ACH RECEPTORS; ALZHEIMERS-DISEASE; MOLECULAR CHARACTERIZATION; CHOLINERGIC HYPOTHESIS; SYNAPTIC-TRANSMISSION; COGNITIVE FUNCTION; DISTINCT SUBTYPES; INTERNEURONS AB Neuronal nicotinic acetylcholine receptors (nAChRs) are involved in a variety of physiological processes, including cognition and development. Dysfunctions in nAChRs have been linked to Alzheimer's disease (AD), a human neurological disorder that is the leading cause of dementia. AD is characterized by an increasing loss of cognitive function, nAChRs, cholinergic neurons, and choline acetyltransferase activity. A major hallmark of AD is the presence of extracellular neuritic plaques composed of the beta-amyloid (A beta(1-42)) peptide; however, the link between A beta(1-42) and the loss of cognitive function has not been established. Many groups have shown direct interactions between A beta(1-42), and nAChR function, however, with differing results. For example, in rat hippocampal CA1 interneurons in slices, we found that A beta(1-42) inhibits nAChR channels directly, and non-alpha 7 receptors were more sensitive to block than alpha 7 receptors. However, some groups have found that alpha 7 subtypes were potently blocked by A beta(1-42), whereas other groups reported that Ap beta(1-42), can activate nAChRs (i.e., both alpha 7 and non-alpha 7 subtypes). To further investigate the link between nAChR function and A beta(1-42), we expressed various subtypes of nAChRs in Xenopus oocytes (e.g., alpha 4 beta 2, alpha 2 beta 2, alpha 4 alpha 5 beta 2, and alpha 7) and found that A beta(1-42) blocked these various non-alpha 7 nAChRs, without any effect on alpha 7 nAChRs. Furthermore, none of these channels was activated by A beta(1-42). The relative block by A beta(1-42) was dependent on the subunit makeup and apparent stoichiometry of these receptors. These data further support our previous findings that A beta(1-42) directly and preferentially inhibits non-alpha 7 nAChRs. C1 NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM yakel@niehs.nih.gov NR 53 TC 43 Z9 43 U1 3 U2 10 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2005 VL 27 IS 1 BP 13 EP 21 DI 10.1385/JMN:27:01:13 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 953SU UT WOS:000231101600002 PM 16055943 ER PT J AU Rychlik, JL Hsieh, M Eiden, LE Lewis, EJ AF Rychlik, JL Hsieh, M Eiden, LE Lewis, EJ TI Phox2 and dHAND transcription factors select shared and unique target genes in the noradrenergic cell type SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Phox2a; Phox2b; dHAND; norepinephrine; dopamine beta-hydroxylase; SH-SY5Y; chromatin immunoprecipitation ID DOPAMINE-BETA-HYDROXYLASE; SYMPATHETIC NEURON DEVELOPMENT; HOMEODOMAIN PROTEINS; NERVOUS-SYSTEM; EXPRESSION; SPECIFICATION; PROMOTER; BINDING; DNA; SUFFICIENT AB The noradrenergic cell type is characterized by the expression of proteins involved in the biosynthesis, transport, and secretion of noradrenaline and is dependent on the sequential and combinatorial expression of numerous transcription factors, including Phox2a, Phox2b, dHAND, GATA2, GATA3, and MASH1 Phox2a and Phox2b transactivate the promoter of the gene encoding the noradrenergic biosynthetic enzyme, dopamine beta-hydroxylase (DBH), and dHAND potentiates the activity of Phox2a. In this study, we use chromatin immuno-precipitation assays to identify target genes of the Phox2 proteins and dHAND. All three proteins are bound to the DBH and PHOX2B promoter regions in SH-SY5Y neuroblastoma cells. The interaction between Phox2a and dHAND is analyzed by fluorescent anisotropy, which demonstrates that dHAND causes an eightfold increase in the affinity of Phox2a for its recognition sites on the DBH promoter region. The Phox2 proteins are not found on the genes encoding other noradrenergic enzymatic or transport proteins but are reciprocally bound to each other's promoters in SH-SY5Y cells. Together with Phox2a and Phox2b, dHAND is bound to the PHOX2B promoter and is also associated with the GATA2 and eHAND genes in the absence of the Phox2 proteins. These results demonstrate the direct interactions of the Phox2 and dHAND transcription factors within a noradrenergic cell type. The Phox2 proteins were found to share all target genes, whereas dHAND binds to genes independently of Phox2a. C1 Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, Portland, OR USA. NIMH, Lab Mol Neurosci, NIH, Bethesda, MD USA. RP Lewis, EJ (reprint author), Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, Portland, OR USA. EM lewis@ohsu.edu OI Eiden, Lee/0000-0001-7524-944X FU NIGMS NIH HHS [GM38686] NR 32 TC 15 Z9 15 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2005 VL 27 IS 3 BP 281 EP 292 DI 10.1385/JMN/27:03:281 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 984DF UT WOS:000233282000004 PM 16280598 ER PT J AU Woods, AS Ciruela, F Fuxe, K Agnati, LF Lluis, C Franco, R Ferre, S AF Woods, AS Ciruela, F Fuxe, K Agnati, LF Lluis, C Franco, R Ferre, S TI Role of electrostatic interaction in receptor-receptor heteromerization SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article; Proceedings Paper CT 2nd Wenner-Gren International Symposium CY SEP 08-11, 2004 CL Stockholm, SWEDEN SP Wenner-Gren Fdn DE heteromers; dopamine D; receptor; NMDA receptor; electrostatic interaction; mass spectrometry ID METABOTROPIC GLUTAMATE RECEPTORS; DOPAMINE D1 RECEPTORS; D-ASPARTATE RECEPTORS; ER RETENTION SIGNAL; CASEIN KINASE-I; NMDA RECEPTOR; ENDOPLASMIC-RETICULUM; ADENOSINE A(2A); NR1 SUBUNIT; BINDING CHARACTERISTICS AB Using pull-down and mass spectrometry experiments, we have previously demonstrated that adenosine A(2A)-dopamine D-2 receptor-receptor heteromerization depends on an electrostatic interaction between an Arg-rich epitope from the third intracellular loop of the D-2 receptor (217RRRRKR222) and two adjacent Asp residues (DD401-402) or a phosphorylated Ser (pS(374)) residue in the carboxyl terminus of the A(2A) receptor. It has been demonstrated recently that a specific region in the carboxyl terminus of the dopamine D, receptor (L-387-L-416) and a specific region in the carboxyl terminus of the NR1-1 subunit of the NMDA receptor (E-834-S-938) are involved in D-1-NMDA receptor-receptor heteromerization. Careful perusal of these interacting regions shows the presence of a phosphorylated serine (pS(397)) and adjacent glutamates (EE404-405) in the D-1 receptor, whereas NR1-1 contains three adjacent Arg residues (RRR893-896). These epitopes are highly conserved in all species, a sign that the epitopes are likely to be involved in a physiologically significant activity. If similar epitopes are found to be involved in the formation of receptor heteromers other than A(2A)-D-2 and D-1-NMDA, the epitope-epitope electrostatic interaction might represent an important general mechanism underlying receptor-receptor interactions. C1 NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Univ Barcelona, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain. Karolinska Inst, Dept Neurosci, Div Cellular & Mol Neurochem, S-17177 Stockholm, Sweden. Univ Modena, Physiol Sect, Dept Biomed Sci, I-41100 Modena, Italy. RP Woods, AS (reprint author), NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, POB 5180, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov RI Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; OI Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Fuxe, Kjell/0000-0001-8491-4288 NR 39 TC 47 Z9 47 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2005 VL 26 IS 2-3 SI SI BP 125 EP 132 DI 10.1385/JMN/26:02:125 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 944FU UT WOS:000230412800004 PM 16012186 ER PT J AU Agnati, LF Guidolin, D Genedani, S Ferre, S Bigiani, A Woods, AS Fuxe, K AF Agnati, LF Guidolin, D Genedani, S Ferre, S Bigiani, A Woods, AS Fuxe, K TI How proteins come together in the plasma membrane and function in macromolecular assemblies - Focus on receptor mosaics SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article; Proceedings Paper CT 2nd Wenner-Gren International Symposium CY SEP 08-11, 2004 CL Stockholm, SWEDEN SP Wenner-Gren Fdn DE protein-protein interactions; Lego property; electrostatic interactions; hydrogen bonds; van der Waals forces; lipophilic groups; lipophobic groups; receptor mosaics; electromagnetic waves ID CENTRAL-NERVOUS-SYSTEM; LIPID RAFTS; HEPTAHELICAL RECEPTORS; COUPLED RECEPTORS; GABA(B) RECEPTOR; ALPHA-SYNUCLEIN; MOLECULAR-BASIS; CELL-MEMBRANE; MODEL; DISEASE AB Some theoretical aspects on structure and function of proteins have been discussed previously. Proteins form multimeric complexes, as they have the capability of binding other proteins (Lego property) resulting in multimeric complexes capable of emergent functions. Multimeric proteins might have either a genomic or a postgenomic origin. Proteins spanning the plasma membrane have been analyzed by considering the effects of the microenvironment in which the protein is embedded. In particular, the different effects of the hydrophilic (extracellular and intracellular) versus the lipophilic (intramembrane) environment have been considered. These aspects have been discussed in the framework of membrane microdomains, in particular, the so-called rafts. In alpha-helix proteins the individual peptide dipoles align to produce a macrodipole crossing the entire membrane. This macrodipole has its positive (extracellular) pole at the N-terminal end of the helix and its negative (intracellular) pole at the C-terminal end. This arrangement has been analyzed in the framework of the counter-ion atmosphere, that is, the formation of a cloud of small ions bearing an opposite charge. Excitable cells reverse their resting potential during the all-or-none action potentials. Hence, the extracellular side of the plasma membrane becomes negative with respect to the intracellular side. This change of polarization affects also the direction and magnitude of the alpha-helix dipole in view of the fact that there is a displacement of the counter ions. The oscillation in the intensity of the dipole caused by the action potentials opens the possibility of an interaction among dipoles by electromagnetic waves. C1 Univ Modena, Dept Biomed Sci, Physiol Sect, I-41100 Modena, Italy. Univ Modena, Dept Biomed Sci, Pharmacol Sect, I-41100 Modena, Italy. Univ Padua, Dept Human Anat & Physiol, Sect Anat, I-35100 Padua, Italy. NIDA, Dept Hlth & Human Serv, Intramural Res Program, Baltimore, MD 21224 USA. Karolinska Inst, Dept Neurosci, SE-17177 Stockholm, Sweden. RP Agnati, LF (reprint author), Univ Modena, Dept Biomed Sci, Physiol Sect, I-41100 Modena, Italy. EM luigiagnati@tin.it RI Ferre, Sergi/K-6115-2014; Bigiani , Albertino/G-3024-2015; Genedani, Susanna/K-4370-2016; OI Ferre, Sergi/0000-0002-1747-1779; Bigiani , Albertino/0000-0001-6987-488X; Genedani, Susanna/0000-0003-1526-153X; Fuxe, Kjell/0000-0001-8491-4288; Guidolin, Diego/0000-0003-2133-3552 NR 77 TC 25 Z9 26 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2005 VL 26 IS 2-3 SI SI BP 133 EP 153 DI 10.1385/JMN/26:02:133 PG 21 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 944FU UT WOS:000230412800005 PM 16012187 ER EF