# projects

application_id: 7610393
project_number: 5P20RR016481-07
project_title: QSAR OF ADRENERGIC RECEPTOR ANTAGONIST
administering_ic: NCRR
award_notice_date: 2007-05-11
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2007-05-01
project_end_date: 2008-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7408
contact_pi_person_id: 8536028
contact_pi: BAUTISTA, DEBRA
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The chloroplast of the common geranium Pelargonium hortorum contains the largest plastid chromosome of any land plant and has undergone numerous structural rearrangements (inversions and transpositions) and gene duplications making this a very active and dynamic genome.  Our working hypothesis was that these extensive structural alterations are due to recombination events mediated by small dispersed repeat elements scattered throughout the genome.  A collaborative effort was initiated with investigators at 3 other institutions (University of Texas/Austin University of California/Berkeley and Indiana University) and the DOE Joint Genome Institute and Lawrence Berkeley National Laboratory to sequence and annotate the entire geranium chloroplast genome.  This effort has now been completed and is being submitted for publication. All likely genes have been annotated several gene losses have been documented and several families of repeat elements have been identified and mapped.  These repeats are located at the borders of rearranged sequences and thus seem likely to mediate recombination events that would lead to rearranged genomes.  Models have been proposed that account for the major genome rearrangements and can be tested by examining related species for intermediate states. In geranium one and possibly two transcriptional operons have been disrupted leading to a potential change in gene regulation.  Despite the increase in size and complexity of the genome the gene content is similar to that of other flowering plants with the exception of a large number of pseudogenes.  These findings have implications for understanding genome structural evolution and gene rearrangements in other circular genomes such as those of human mitochondria.

project_terms:
Accounting;Adrenergic Antagonists;Angiosperms;California;Chloroplasts;Chromosomes;Computer Retrieval of Information on Scientific Projects Database;DNA Sequence Rearrangement;Elements;Event;Evolution;Family;Funding;Gene Duplication;Gene Expression Regulation;Gene Rearrangement;Genes;Genome;Geranium;Grant;Human;Indiana;Institutes;Institution;Joints;Laboratories;Lead;Maps;Mediating;Mitochondria;Modeling;Numbers;Operon;Pelargonium;Plants;Plastids;Pseudogenes;Publications;Recombination Genetic;Research;Research Personnel;Resources;Source;Testing;Texas;United States National Institutes of Health;Universities;Work;austin;size


application_id: 7610382
project_number: 5P20RR016481-07
project_title: INBRE COLLABORATION
administering_ic: NCRR
award_notice_date: 2007-05-11
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2007-05-01
project_end_date: 2008-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7397
contact_pi_person_id: 7326029
contact_pi: DAVIS, CHERYL D
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.During this project year a collaborative project was initiated with Dr. Abdelnaby Khalyfa and Dr. Nigel Cooper of the School of Medicine at the University of Louisville Health Sciences Center.

project_terms:
Collaborations;Computer Retrieval of Information on Scientific Projects Database;Funding;Grant;Health Sciences;Institution;Research;Research Personnel;Resources;Schools Medical;Source;United States National Institutes of Health;Universities


application_id: 7610376
project_number: 5P20RR016481-07
project_title: BRIN: UL: KENTUCKY BRIN ADMINISTRATIVE CORE
administering_ic: NCRR
award_notice_date: 2007-05-11
opportunity_number: RFA-RR-03-108
application_type: 5
activity_code: P20
ic: RR
serial_number: 016481
project_start_date: 2007-05-01
project_end_date: 2008-04-30
study_section: ZRR1-RI-7(01)
subproject_number: 7391
contact_pi_person_id: 1866398
contact_pi: COOPER, NIGEL G
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The administrative core provides a leadership role in the development and support of KBRIN activities and provides logistical support for KBRIN committees and activities. The KBRIN administrative office works with the Grants Management Office at the University of Louisville for the development of subcontracts to KBRIN affiliates.

project_terms:
Computer Retrieval of Information on Scientific Projects Database;Development;Funding;Grant;Institution;Kentucky;Leadership;Office Management;Office of Management;Research;Research Personnel;Resources;Role;Source;United States National Institutes of Health;Universities;Work


application_id: 7609765
project_number: 5P20RR015576-08
project_title: HEAT SHOCK PROTEINS IN SPINAL CORD NEURAL SURVIVAL
administering_ic: NCRR
award_notice_date: 2007-06-06
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015576
project_start_date: 2007-06-01
project_end_date: 2008-05-31
study_section: ZRR1-RI-8(02)
subproject_number: 6784
contact_pi_person_id: 6155708
contact_pi: GOZAL, EVELYNE
other_pis: Not Applicable
congressional_district: 03
department: NEUROSURGERY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.Spinal cord injury (SCI) and subsequent secondary cell death partially involves an ischemic component. Oligodendrocytes and astrocytes survival is critical to maintain cellular interactions in the white matter and limit secondary injury damage. The purpose of this proposal is to study heat shock proteins (hsps) induction and interactions in hypoxia/ischemia-exposed oligodendrocytes and astrocytes and identify molecules and signaling pathways associated with higher tolerance to ischemia. Hsps induced by various stresses are involved in protein refolding and repair and have been implicated in cellular ischemic tolerance in brain and in spinal cord. We will test the hypothesis that after SCI induction of hsp expression modulates glial cell survival signaling pathways to preserve oligodendrocyte / astrocyte integrity and interactions with neurons. The specific aims of this proposal are: 1. To examine the expression profile of heat shock proteins induced in hypoxic/ischemic oligodendrocytes and astrocytes in culture and in contused spinal cord. 2. To determine the effect of hsp on oligodendrocytes and astrocytes survival to hypoxia/ ischemic injury and after SCI. 3. To determine the mechanism(s) of hsp-related cell protection and the role of hsp binding proteins in hypoxia/ ischemia survival pathways and in cell death after SCI. Using embryonic oligodendrocyte precursors (OPCs) differentiated to either oligodendrocytes or astrocytes and exposed to hypoxia/ischemia we will assess heat shock proteins expression in a cellular model and correlate the levels of hsp expression with cell survival. In addition we will characterize the profile of hsps induced by SCI in rodent spinal cord. The effect of hsp gene overexpression or silencing on oligodendrocytes/astrocytes survival to cellular hypoxia/ ischemia and on SCI-induced delayed injury will be determined as well as the effect of experimental hsp induction in the whole animal on secondary injury-induced damage after SCI. Finally we will use proteomic approaches to identify protein-protein interactions with hsps induced by hypoxia/ischemia in oligodendro- cytes and in astrocytes and in differentially damaged areas of the spinal cord after SCI. Thus we will characterize signaling pathways underlying cellular differential sensitivity to hypoxia/ischemia and identify potential intervention targets in SCI. These studies will identify novel therapeutic approaches to preserve oligodendroglial support in injured spinal cord inhibit apoptosis and reduce delayed white matter injury.

project_terms:
Animals;Apoptosis;Area;Astrocytes;Binding Proteins;Brain;Cell Death;Cell Survival;Cell model;Computer Retrieval of Information on Scientific Projects Database;Cytoprotection;Embryo;Funding;Genes;Grant;Heat shock proteins;Hypoxia;Hypoxia-Ischemia Brain;Injury;Institution;Intervention;Ischemia;Molecular Profiling;Neuroglia;Neurons;Oligodendroglia;Pathway interactions;Protein Overexpression;Proteins;Proteomics;Purpose;Research;Research Personnel;Resources;Rodent;Role;Signal Pathway;Source;Spinal Cord;Spinal cord injury;Stress;Testing;United States National Institutes of Health;novel therapeutics;oligodendrocyte precursor;protein expression;protein protein interaction;relating to nervous system;repaired;white matter;white matter injury


application_id: 7609762
project_number: 5P20RR015576-08
project_title: COBRE: UL: STUDY THE ROLE OF LINGO01 IN VIVO SPINAL CORD REPAIR (SUB PKC)
administering_ic: NCRR
award_notice_date: 2007-06-06
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015576
project_start_date: 2007-06-01
project_end_date: 2008-05-31
study_section: ZRR1-RI-8(02)
subproject_number: 6781
contact_pi_person_id: 7936903
contact_pi: SHIELDS, CHRISTOPHER B
other_pis: Not Applicable
congressional_district: 03
department: NEUROSURGERY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.We have changed the direction of our research project since the last report. LINGO-1 an inhibitory molecule and part of the Nogo receptor complex is involved in CNS repair following spinal cord injury (SCI). This molecule transduces inhibitory signals intracellularly resulting in inhibition of axon growth. LINGO-1 signaling is modulated using LINGO-1 KO mice DN LINGO-1 and LINGO-1 antibody in vivo (we demonstrated that DN LINGO-1 inhibition enhances the rate of MEP return following SCI).  We hypothesize that negative regulation of LINGO-1 will enhance axon regrowth remyelination and functional improvement. LINGO-1 manipulation in vivo SCI may provide new strategies to treat SCI.

We will study LINGO-1 expression under normal conditions and following SCI at different points in time and topographic sites. Temporal expression of LINGO-1 will be studied after contusion and demyelinating SCI (rRT-PCR 4hr 1d 3d. Western blot at 1d 3d 1wk. 3wks). This aim should provide insights into mammalian CNS LINGO-1 signal modulation after SCI. Negative regulation of LINGO-1 in experimental demyelination may increase the degree and rate of remyelination. Using a mouse spinal cord demyelination model in vivo we will study whether axonal conduction morphological and behavioral tests we asked whether LINGO-1 inhibition facilitates myelination. Does LINGO-1 mutation produces a greater number of immature oligodendrocytes and oligodendricytes precursor cells (OPC) or is myelin thickness enhanced? LINGO-1 reduces RhoA activation that prevents axon regeneration.  We hypothesize that RhoA is upregulated during remyelination. We will also evaluate the effect of LINGO-1 inhibition on axon regeneration and collateral sprouting in a region remote from the SCI specifically in the area of the central pattern generator (CPG) in the thoracolumbar area of the spinal cord.

project_terms:
Antibodies;Area;Axon;Blotting Western;Centers of Research Excellence;Complex;Computer Retrieval of Information on Scientific Projects Database;Condition;Contusions;Demyelinations;Funding;Grant;Institution;Mus;Mutation;Myelin;Numbers;Oligodendroglia;Rate;Regulation;Repair of spinal cord;Reporting;Research;Research Personnel;Research Project Grants;Resources;Role;Signal Transduction;Site;Source;Spinal Cord;Spinal cord injury;Thick;Time;United States National Institutes of Health;axon growth;axon regeneration;behavior test;central pattern generator;functional improvement;in vivo;in vivo Model;insight;myelination;precursor cell;prevent;receptor;repaired


application_id: 7609761
project_number: 5P20RR015576-08
project_title: COBRE: UL: MICROSCOPY CORE: CORE E
administering_ic: NCRR
award_notice_date: 2007-06-06
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015576
project_start_date: 2007-06-01
project_end_date: 2008-05-31
study_section: ZRR1-RI-8(02)
subproject_number: 6780
contact_pi_person_id: 6492007
contact_pi: ROISEN, FRED JERROLD
other_pis: Not Applicable
congressional_district: 03
department: NEUROSURGERY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The purpose of CORE E:  Microscopy is to provide all projects with the personnel facilities resources and supplies to perform confocal TEM and SEM microscopy  The procedures that will be available include tissue processing for plastic sectioning plastic sectioning and staining and immunofluorescence staining.  Assistance and the expertise will be available for developing specialized microscopy procedures.

project_terms:
Centers of Research Excellence;Computer Retrieval of Information on Scientific Projects Database;Funding;Grant;Human Resources;Immunologic Immunofluorescence;Institution;Microscopy;Plastics;Procedures;Purpose;Research;Research Personnel;Resources;Source;Staining method;Stains;United States National Institutes of Health;tissue processing


application_id: 7609760
project_number: 5P20RR015576-08
project_title: COBRE: MECHANISMS OF PLASTICITY & REPAIR AFTER SCI D: BEHAV & ELECTROPHYS CORE
administering_ic: NCRR
award_notice_date: 2007-06-06
opportunity_number: RFA-RR-04-008
application_type: 5
activity_code: P20
ic: RR
serial_number: 015576
project_start_date: 2007-06-01
project_end_date: 2008-05-31
study_section: ZRR1-RI-8(02)
subproject_number: 6779
contact_pi_person_id: 1932676
contact_pi: MAGNUSON, DAVID SK
other_pis: Not Applicable
congressional_district: 03
department: NEUROSURGERY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The purpose of the Electrophysiology and Behavior CORE (CORE D) is to provide a battery of standard tests to assess the function of animals and their spinal cords after injury and treatment and to facilitate the development of more specialized tests that may be needed for the COBRE projects.  The CORE will provide the following tests:  1. Transcranial magnetic motor evoked potentials (tcMMEPs) to assess action potential conduction in descending axons located in the ventrolateral funiculus in rats and mice.  2. Somatosensory evoked potentials (SSEPs) to assess ascending primary sensory pathways (rats only). 3. Magnetic interenlargement reflexes (MIERs) to assess conduction in ascending propriospinal axons located in the lateral white matter (rats only). 4. Open Field Locomotor Scale (BBB) to assess hindlimb function during overground locomotioin in rats and the Basso Mouse Scale (BMS) for mice. 5. A grid-walking test to assess sensorimotor function. 6. The Louisville Swimming Scale (LSS; rats only) to assess hindlimb function during swimming. 7. Hindlimb kinematics during overground locomotion and swimming for rats and mice using joint angle limb excursion and step cycle duration as primary measures. 8. The Hargreave's test to assess cutaneous hyperalgesia. 9. Electro von Frey hairs to assess mechano-hypersensitivity after injury.  In addition the CORE will pursue the development of novel electrophysiological and behavioral assessment tools as needed by specific projects within the COBRE laboratires.

project_terms:
Action Potentials;Animals;Axon;Behavior;Behavior assessment;Centers of Research Excellence;Computer Retrieval of Information on Scientific Projects Database;Cutaneous;Development;Electrophysiology (science);Evoked Potentials Motor;Funding;Grant;Hair;Hindlimb;Hyperalgesia;Hypersensitivity;Injury;Institution;Joints;Lateral;Limb structure;Locomotion;Magnetism;Measures;Mus;Pathway interactions;Purpose;Rattus;Reflex action;Research;Research Personnel;Resources;Sensorimotor functions;Sensory;Somatosensory Evoked Potentials;Source;Spinal Cord;Standards of Weights and Measures;Swimming;Testing;United States National Institutes of Health;Walking;kinematics;novel;repaired;tool;white matter


application_id: 7609154
project_number: 5R01CA111987-05
project_title: Sphingosine Kinase Compartmentalization in Tumorogenesis
administering_ic: NCI
award_notice_date: 2009-04-06
application_type: 5
activity_code: R01
ic: CA
serial_number: 111987
program_official: YASSIN, RIHAB R
project_start_date: 2005-07-15
project_end_date: 2010-04-30
study_section: Cancer Etiology Study Section[CE]
contact_pi_person_id: 1923480
contact_pi: WATTENBERG, BRIAN W.
other_pis: Not Applicable
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-05-01
project_abstract:
DESCRIPTION (provided by applicant): The long-range goal of the proposed research is to identify molecular targets in sphingolipid signaling pathways for the development of therapeutics to treat cancer. The focus of the present proposal is the signaling enzyme sphingosine kinase-1 which produces the potent second messenger sphingosine-1-phosphate. Sphingosine kinase represents a candidate target for cancer therapy. This concept is based on the observations that sphingosine kinase is overexpressed in many tumors and that experimental overproduction of sphingosine kinase transforms cells from a growth-controlled state to a tumorigenic state. The localization of sphingosine kinase to distinct intracellular sites is key to its ability to transform cells. The proposed experimental plan will determine why localization is important for transformation. This will form the basis for a discovery of novel molecular targets involved in the transforming ability of sphingosine kinase. To accomplish this goal three specific aims are proposed. Specific Aim 1. Determine the activation-dependent subcellular localization of sphingosine kinase and sphingolipid metabolites affected by SK activity. Specific Aim 2. Determine the role of SK localization in cellular transformation and protumorigenic pathways. Specific Aim 3. The plasma membrane sphingosine-1-phosphate transport mechanism. Determine the mechanism and functional effects of enhanced sphingosine-1-phosphate secretion by activation of hSK-1.

project_terms:
Address;Affect;Agonist;Apoptotic;Binding (Molecular Function);Biochemical;Cell Proliferation;Cell membrane;Cell physiology;Cell secretion;Cellular Membrane;Ceramides;Cytosol;Data;Elements;Endoplasmic Reticulum;Enzymes;Experimental Models;Experimental Neoplasms;Future;Goals;Growth;Housekeeping;Human;Intracellular Membranes;Knowledge;Laboratories;Lead;Lipids;Malignant Neoplasms;Mediating;Membrane;Molecular;Molecular Target;Movement;Oncogenic;Pathway interactions;Phosphorylation;Process;Production;Proteins;Receptor Activation;Regulation;Research;Research Personnel;Role;SPHK1 enzyme;Second Messenger Systems;Signal Pathway;Signal Transduction;Signaling Molecule;Site;Specificity;Sphingolipids;Sphingosine;Sphingosine-1-Phosphate Receptor;Testing;Therapeutic;Time;Work;base;cancer therapy;carcinogenesis;cell transformation;clinical application;design;extracellular;inhibitor/antagonist;inorganic phosphate;lipid transport;member;metaplastic cell transformation;novel;overexpression;programs;second messenger;sphingosine 1-phosphate;sphingosine kinase;therapeutic development;tool;trafficking;tumor growth;tumorigenesis;tumorigenic


application_id: 7608700
project_number: 5R21DA024089-02
project_title: Human Lab Model of Behavioral/Pharmacological Treatment for Cocaine Dependence
administering_ic: NIDA
award_notice_date: 2009-03-31
opportunity_number: PA-06-181
application_type: 5
activity_code: R21
ic: DA
serial_number: 024089
program_official: BOUGH, KRISTOPHER J
project_start_date: 2008-04-10
project_end_date: 2011-09-30
study_section: ZDA1-RXL-E(03)
contact_pi_person_id: 7577019
contact_pi: STOOPS, WILLIAM WALTON
other_pis: Not Applicable
congressional_district: 06
department: PSYCHOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
DESCRIPTION (provided by applicant): Cocaine dependence continues to be a significant public health concern. Data from the National Survey on Drug Use and Health indicate that the number of Americans who had used cocaine in the past month has remained relatively stable since 2002 and cocaine remains the most frequently mentioned drug in emergency-room admissions according to the Drug Abuse Warning Network. Because of the public-health concerns and costs associated with its abuse identifying a pharmacotherapy for the treatment of cocaine dependence is a priority for the National Institute on Drug Abuse (NIDA). Despite intense research efforts a widely accepted medication for cocaine dependence has not yet been identified. A number of non-pharmacological treatments for cocaine dependence have also been examined. Specifically behavioral treatments for cocaine dependence seek to reinforce non- drug related behaviors. For example contingency management uses monetary incentives to decrease cocaine use and is associated with high rates of prolonged cocaine abstinence. Given the effectiveness but also high relative cost of behavioral treatments for cocaine dependence some have theorized that pharmacotherapies may be able to enhance the effectiveness of behavioral therapies and decrease costs associated with delivery of these therapies. Indeed pharmacotherapies (i.e. desipramine and bupropion) have been shown to enhance the effectiveness of behavioral therapies for cocaine dependence. The purpose of the experiments proposed in this application is to "reverse engineer" a human laboratory model of combined pharmacological and behavioral treatments for cocaine dependence using an already existing and validated model of contingency management the cocaine versus money choice paradigm. The research proposed in this application has two specific aims. The first specific aim is to adapt a model of the cocaine versus money choice paradigm that is sensitive to pharmacological pretreatment (Higgins et al. 1996) and determine optimal parameters (i.e. cocaine dose monetary values). In Experiment 1 eight non-treatment seeking cocaine-dependent subjects will choose between a range of doses of intranasal cocaine and monetary values. These data will be used to guide which cocaine dose and monetary values will be used in Experiment 2. The second specific aim is to validate the sensitivity of the cocaine versus money choice paradigm as a model of combined pharmacological and behavioral treatment. In Experiment 2 eight non-treatment seeking cocaine-dependent subjects will choose between a range of doses of intranasal cocaine and monetary values following maintenance for seven days on placebo or 300 mg bupropion. The research proposed in this application will serve to develop an efficient and valid human laboratory screen of medications for cocaine dependence. Project Narrative The research proposed in this application seeks to develop a model of combined behavioral and pharmacological treatment for cocaine dependence. With this model we hope to more efficiently screen medications that might enhance the efficacy of contingency management a behavioral treatment that is successful in managing cocaine dependence.

project_terms:
Abstinence;Accident and Emergency department;Admission activity;American;Behavior;Behavior Therapy;Behavioral Model;Bupropion;Clinical Trials;Cocaine;Cocaine Dependences;Combined Pharmacological and Behavioral Treatment;Crime;Data;Desipramine;Dose;Drug abuse;Drug usage;Educational process of instructing;Effectiveness;Engineering;Equilibrium;Future;Health;Human;Incentives;Laboratories;Maintenance;Medical;Modeling;Monitor;National Institute of Drug Abuse;Pharmaceutical Preparations;Pharmacological Treatment;Pharmacotherapy;Placebos;Population;Productivity;Relapse;Relative (related person);Reporting;Research;Societies;Surveys;Testing;Treatment Cost;Treatment Effectiveness;cocaine use;contingency management;cost;economic value;non-drug;public health medicine (field);research study;skills;voucher


application_id: 7607362
project_number: 3M01RR002602-22S1
project_title: CREATINE IN PARTICIPANTS WITH TREATED PARKINSON'S DISEASE
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5372
contact_pi_person_id: 1868189
contact_pi: CAMBI, FRANCA
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The primary study aim of this trial is to compare the primary outcome as measured by the Schwab and England ADl (PD function) PDQ-39 (QOL) ambulatory capacity (sum of 5 UPDRS questions: falling freezing walking gait postural stablity) Symbol Digit Modalities (cognative impairment) and Modified Rankin Value (global functioning) in the creatine group versus the placebo group against a background of dopaminergic therapy and best medical care. The research hypothesis is that the group being treated with creatine will show less disease progression by 5 years than the group on placebo as evalutated by a Global Statistical Test comprised of the above measures. Secondard aims are to compare the creaine and placebo groups on additaional measure of efficacy safety and tolerability using data between baseline and 5 years follow up.

project_terms:
Caring;Computer Retrieval of Information on Scientific Projects Database;Creatine;Data;Digit structure;Disease Progression;England;Freezing;Funding;Gait;Grant;Impairment;Institution;Measures;Medical;Modality;Outcome;Parkinson Disease;Participant;Placebos;Quality of life;Research;Research Personnel;Resources;Safety;Source;Sum;Testing;United States National Institutes of Health;Walking;falls;follow-up


application_id: 7607361
project_number: 3M01RR002602-22S1
project_title: IMMUNOTOXICITY OF ZIDOVUDINE PLUE SULFAMETHOXAZOLE-TRIMETHOPRIM EXPOSURE
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5371
contact_pi_person_id: 8968639
contact_pi: FEOLA, DAVID
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.HIV-infected individuals endure an immunodeficiency syndrome that has been well-described.  However the fate of B lymphocytes in this population remains underappreciated.  Despite having elevated IgG titers HIV-infected individuals have an impaired ability to produce specific antibodies in response to neo-antigens.  Previous work in mice suggests that simultaneous exposure to zidovudine (ZDV) and sulfamethoxazole-trimethoprim (SMX-TMP) causes a synergistic immunotoxicity specifically to the ability to produce an antigen-specific antibody response.  Pilot clinical data from our group shows that ZDV plus SMX-TMP exposure impacts influenza-specific serum IgG titers in HIV-infected subjects post-vaccination and eliminates the positive correlation typically observed between IgG titers and CD4+ counts.  Decreased proliferation and antibody production have been demonstrated in B cells responding to T cell-independent B cell mitogens in individuals infected with HIV.  Our hypothesis is that exposure to ZDV plus SMX-TMP contributes to the B cell defects observed among HIV-infected individuals.  We aim to 1) evaluate ex vivo proliferation antibody production and cytokine secretion of B and T cells isolated from subjects treated with ZDV plus SMX-TMP and 2) differentiate whether this immunotoxicity affects innate B cell function T cell help or both.  Subjects will be recruited from the University of Kentucky Bluegrass Care Clinic who are HIV infected receiving combination antiretroviral therapy that includes ZDV have CD4+ counts greater than 350 cells/l and undetectable viral loads.  Fifteen patients who grant informed consent will be included in the final analysis.  Each subject will be given a 30-day experimental course of SMX-TMP (1 double-strength tablet daily).  Blood will be obtained from each subject by venipuncture at the beginning and at the end of treatment.  Peripheral blood mononuclear cells will be isolated by Ficoll gradient purification for analysis.  Data from before and after treatment will be compared with each subject serving as his or her own control.  Cells will be cultured with mitogens of different types to stimulate proliferative and antibody responses as follows:  pokeweed antigen (T cell-dependent B cell mitogen) Staphylococcus aureus Cowan (T cell-independent B cell mitogen) and phytohemagglutinin A (T cell mitogen).  Proliferation will be assayed by hemocytometric enumeration.  Antigen-specific antibody responses will be measured by an ELISA assay of the collected culture supernatants quantifying titers of IgG and IgM.  The number of antigen-specific antibody secreting cells will be determined by an ELISPOT technique.  Further T cells will be assayed for their ability to secrete cytokines including tumor necrosis factor-a interferon-g interleukin (IL)-2 and IL-4 by utilizing cytometric bead array technology and flow cytometry.  These data will provide evidence as to the mechanism of this drug toxicity in humans by examining the functionality of B and T cells in this in vitro context.  Clinicians involved in the treatment of patients in this population will benefit from the knowledge of additional immunosuppression this drug combination may cause.

project_terms:
Affect;Aftercare;Antibodies;Antibody Formation;Antigens;B-Lymphocytes;Biological Assay;Blood;CD4 Lymphocyte Count;Caring;Cell physiology;Cells;Clinic;Clinical Data;Computer Retrieval of Information on Scientific Projects Database;Daily;Data;Defect;Drug Combinations;Drug toxicity;Enzyme-Linked Immunosorbent Assay;Exposure to;Ficoll;Flow Cytometry;Funding;Grant;HIV;Human;Immunoglobulin G;Immunoglobulin M;Immunoglobulin-Secreting Cells;Immunologic Deficiency Syndromes;In Vitro;Individual;Influenza;Informed Consent;Institution;Interferons;Interleukin-2/Interleukin-4;Kentucky;Knowledge;Measures;Mitogens;Mus;Natural immunosuppression;Numbers;Patients;Peripheral Blood Mononuclear Cell;Personal Satisfaction;Phytohemagglutinins;Phytolacca americana;Poa plant;Population;Recruitment Activity;Research;Research Personnel;Resources;Serum;Source;Staphylococcus aureus;T-Lymphocyte;TNF protein human;Tablets;Techniques;Technology;Therapeutic immunosuppression;Trimethoprim-Sulfamethoxazole Combination;Tumor Necrosis Factor-alpha;Tumor Necrosis Factors;United States National Institutes of Health;Universities;Vaccination;Venipunctures;Viral Load result;Work;Zidovudine;antiretroviral therapy;cytokine;day;enzyme linked immunospot assay;immunotoxicity;response


application_id: 7607360
project_number: 3M01RR002602-22S1
project_title: PRENATAL PASSIVE EXPOSURE AND PREGNANCY OUTCOMES
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5370
contact_pi_person_id: 9342359
contact_pi: ASHFORD, KRISTIN
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The purpose of this study is to examine the relationship between level of prenatal passive smoke exposure and birth outcomes using hair nicotine analysis. The long-term objective of this research is to develop effective interventions to reduce prenatal exposure to passive smoke. With increased knowledge regarding the adverse health effects of passive smoke on fetal and infant health mothers may take additional precautions to avoid exposure during pregnancy. A correlational cross-sectional non-experimental study using a quota sampling design will be used. A multiethnic population of 200 pregnant women will be recruited to participate. Data will be collected on self-reported secondhand smoke (SHS) exposure smoking history home smoking policy depressive symptoms fetal health locus of control (FHLC) nicotine levels in maternal and infant hair and birth outcomes. Birth outcome data includes: birthweight gestational age method of delivery delivery complications and immediate newborn complications. All data will be collected during the immediate postpartum period (1-4 days following delivery). Participants will be asked to provide a hair sample for nicotine measurement of prenatal SHS exposure and a urine sample to validate smoking status. Newborn hair samples will also be collected and matched to their mother's sample. This research is critical for advancing the science of biomarker usage for measuring prenatal SHS smoke exposure in order to correctly identify and quantify adverse effects of exposure on birth outcome.

project_terms:
Adverse effects;Biological Markers;Birth;Computer Retrieval of Information on Scientific Projects Database;Control Locus;Data;Exposure to;Funding;Gestational Age;Grant;Hair;Health;Health Infant;Home environment;Infant;Infant Newborn;Institution;Intervention;Knowledge;Measurement;Measures;Methods;Mothers;Nicotine;Outcome;Participant;Passive Smoking;Patient Self-Report;Policies;Population;Postpartum Period;Pregnancy;Pregnancy Outcome;Pregnant Women;Purpose;Recruitment Activity;Research;Research Personnel;Resources;Sampling;Science;Smoke;Smoking;Smoking History;Smoking Status;Source;United States National Institutes of Health;Urine;day;depressive symptoms;design;fetal;prenatal;prenatal exposure;research study


application_id: 7607359
project_number: 3M01RR002602-22S1
project_title: MOMAS
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5369
contact_pi_person_id: 9219630
contact_pi: TEMPRANO, JAMES
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.Asthma and smoking during pregnancy cause significant morbidity in both the mother and the offspring. Asthma represents the most common respiratory disorder during pregnancy and smoking rates during pregnancy range from 15-30% in the United States.  Maternal asthma and smoking during pregnancy have been shown to increase the rate of intrauterine growth retardation and preterm delivery as well as increase the risk of wheeze asthma respiratory infections and otitis media in children.  However controlled asthmatics during pregnancy have similar outcomes to non-asthmatic pregnancies.  Measurement of the fractional concentration of exhaled nitric oxide (FENO) is a new easily performed non-invasive method that has been used to assess airway inflammation in adults and children.  The long term goal of this study is to establish baseline FENO values and to monitor airway disease in pregnant asthmatics pregnant smokers and pregnant controls and to correlate these levels with other inflammatory markers in the mothers and their offspring.  These values will be correlated with current methods to diagnose and monitor disease control in these patients.  The use of FENO levels in the pregnant asthmatic may prove to be a better method for monitoring disease control and titrating steroid doses in this population thus maximizing the benefit of these medications while minimizing possible side-effects to the mother and fetus.  Finally this study may identify children at higher risk of developing asthma or allergic disease.  This could serve to identify factors that may be modified to prevent or limit the development of these diseases in this population.

project_terms:
Adult;Adverse effects;Allergic;Asthma;Child;Computer Retrieval of Information on Scientific Projects Database;Development;Diagnosis;Disease;Dose;Exhalation;Fetal Growth Retardation;Fetus;Funding;Goals;Grant;Inflammatory;Institution;Invasive;Lung diseases;Measurement;Methods;Monitor;Morbidity - disease rate;Mothers;Nitric Oxide;Otitis Media;Outcome;Patient currently pregnant;Patients;Pharmaceutical Preparations;Population;Pregnancy;Premature Birth;Range;Rate;Research;Research Personnel;Resources;Respiration Disorders;Respiratory Tract Infections;Risk;Smoking;Source;Steroids;United States;United States National Institutes of Health;Wheezing;airway inflammation;disorder control;fetal tobacco exposure;prevent


application_id: 7607358
project_number: 3M01RR002602-22S1
project_title: EFFECT OF CARBOHYDRATE ON GHRELIN AND PEPTIDE YY IN PREPUBERTAL CHILDREN
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5368
contact_pi_person_id: 8650215
contact_pi: LOMENICK, JEFFERSON P
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.Obesity has become a worldwide problem and more than 30% of children in the United States are now overweight or at risk for overweight.  In the last few years much has been learned about the neuroendocrine control of appetite and weight specifically the role of gut hormones such as ghrelin and peptide YY (PYY).  The effects of specific nutritional factors on secretion of these hormones have been investigated to a limited degree in adults though almost no data is available in children.  Preliminary work of my own indicates that lean and overweight prepubertal children exhibit a much different pattern of secretion of these gut hormones in response to eating a mixed meal than do adults.  Thus children may also secrete these gut hormones differently in response to various macronutrients than the pattern seen in adults which may have a great impact on potential therapies for childhood obesity.  I propose to evaluate the ghrelin and PYY response following administration of carbohydrate in a group of prepubertal children in order to improve our understanding of how appetite and energy balance are regulated.

project_terms:
Adult;Carbohydrates;Child;Childhood;Computer Retrieval of Information on Scientific Projects Database;Data;Desire for food;Eating;Exhibits;Funding;Grant;Hormones;Institution;Learning;Neurosecretory Systems;Nutrition Macronutrients;Nutritional;Obesity;Overweight;Pattern;Peptide YY;Peptides;Research;Research Personnel;Resources;Risk;Role;Source;United States;United States National Institutes of Health;Weight;Work;energy balance;ghrelin;improved;response


application_id: 7607357
project_number: 3M01RR002602-22S1
project_title: OBESITY AND PERIPHERAL ARTERIAL DISEASE
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5367
contact_pi_person_id: 9342366
contact_pi: ZIADA, KHALED
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.In the United States and other industrialized countries obesity has reached epidemic proportions over the last few decades.  Numerous epidemiologic studies have linked obesity to an increasing risk of cardiovascular events strokes and cardiac death.  The mechanisms by which obesity leads to such adverse outcomes remain unclear.  In addition to the indirect mechanisms such as increasing the risk of diabetes hypertension and dyslipidemia there is also evidence of an independent deleterious effect of obesity on the heart and vasculature.  More recently the effect of body fat distribution (central versus peripheral adiposity) has gained attention.  Central obesity caused by accumulation of metabolically active visceral fat and expressed as increasing waist circumference was more tightly linked to development of cardiovascular risk factors adverse cardiac events and strokes than the mere increase in body mass index which has been the traditional expression of obesity.  

Despite the growing recognition of the role of obesity in predisposing to adverse cardiovascular events few studies addressed its association with peripheral arterial disease (PAD).  In those few investigations there has been no association between increasing body mass index and clinical evidence of PAD but a significant association between waist-hip ratio and reduced ankle-brachial index and/or history of claudications was demonstrated in patients <65 years of age.  There has been no study addressing the relationship between waist circumference and evidence of sub-clinical or early PAD.

We hypothesize that there is a measurable association between obesity and development of PAD.  It is likely that this association is more discernable among patients <75 years old and in whom a more direct and earlier evidence of PAD can be identified.  For that we propose a study in which intravascular ultrasound imaging of the iliac artery can be utilized to quantify early evidence of atherosclerotic burden.  This quantitative measure of PAD can then be correlated with evidence of central obesity as expressed by increasing waist circumference and/or visceral fat area as measured on computerized tomographic scans of the abdomen (abdominal CT).  In addition we propose correlating PAD burden as defined by ultrasound imaging with plasma levels of leptin a peptide with several vascular effects that is known to be secreted by adipocytes and other adipocyte related and/or inflammatory markers.

project_terms:
Abdomen;Address;Adipocytes;Age-Years;Ankle;Area;Attention;Blood Vessels;Body fat;Body mass index;Cardiac;Cardiovascular system;Central obesity;Clinical;Computer Retrieval of Information on Scientific Projects Database;Death Cardiac;Developed Countries;Development;Dyslipidemias;Epidemic;Epidemiologic Studies;Event;Fatty acid glycerol esters;Funding;Grant;Heart;Hypertension;Inflammatory;Institution;Investigation;Leptin;Link;Measurable;Measures;Obesity;Outcome;Patients;Peptides;Peripheral;Peripheral arterial disease;Plasma;Recording of previous events;Research;Research Personnel;Resources;Role;Scanning;Source;Structure of iliac artery;Ultrasonography;United States;United States National Institutes of Health;Visceral;Waist-Hip Ratio;cardiovascular risk factor;claudication;computerized;diabetes risk;indexing;stroke;waist circumference


application_id: 7607356
project_number: 3M01RR002602-22S1
project_title: ANTI-OXIDANT TREATMENT IN AD
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5366
contact_pi_person_id: 1900844
contact_pi: JICHA, GREGORY A
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.To assess the safety and tolerability of two regimens of antioxidant supplements in comparision to placebo in participants with mild to moderate AD. The active regimens consist of vitamin E 800 mg + vitamin C 200 mg + a-lipoic acid 600 mg given once per day and coenzyme Q10 800 mg three times a day (TID). To measure the effects of treatment with antioxidants on cerebrospinal fluid (CSF) biomarkers of oxidative damage namely isoprostanes  and neurodegeneration namely tau and phosphotau 181.

project_terms:
Antioxidants;Ascorbic Acid;Biological Markers;Cerebrospinal Fluid;Coenzyme Q10;Computer Retrieval of Information on Scientific Projects Database;Funding;Grant;Institution;Isoprostanes;Measures;Nerve Degeneration;Participant;Placebos;Protocols Treatment;Research;Research Personnel;Resources;Safety;Source;Thioctic Acid;Time;United States National Institutes of Health;Vitamin E;day;tau Proteins;treatment effect


application_id: 7607355
project_number: 3M01RR002602-22S1
project_title: EFFECTS OF DHA
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5365
contact_pi_person_id: 1900844
contact_pi: JICHA, GREGORY A
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.Primary Aim: To determine whether treatment with DHA 1 gram bid improves cognitive function in patients with AD as indicated by changes in scores on the ADAS-Cog and CDR-SOB. 
Secondary Aims: 
1.To determine if chronic DHA supplementation exerts anti-amyloid antioxidant or neuroprotective effects using validated biomarkers of these mechanisms (MRI-derived rates of brain atrophy CSF beta amyloid tau p-tau F2 isoprostanes and neuroprostanes).
2.To determine the effects of chronic DHA supplementation on plasma and urine biomarkers of oxidative damage (plasma F4 neuroprostanes and urine F2 isoprostanes).
3.To determine the effects of chronic DHA supplementation on other relevant micronutients and their role in AD progression (Vitamin C Vitamin E carotenoids).
4.To determine the effect of chronic DHA supplementation on measures of functional impairment (ADCS-ADL) psychiatric comorbidities in AD (NPI) and quality of life (QOL).

project_terms:
Amyloid;Amyloid beta-Protein;Antioxidants;Ascorbic Acid;Biological Markers;Carotenoids;Chronic;Comorbidity;Computer Retrieval of Information on Scientific Projects Database;Docosahexaenoic Acids;F2-Isoprostanes;Funding;Grant;Institution;Measures;Patients;Plasma;Quality of life;Rate;Research;Research Personnel;Resources;Role;Score;Source;Supplementation;United States National Institutes of Health;Urine;Vitamin E;cerebral atrophy;cognitive function;functional disability;improved;tau Proteins


application_id: 7607354
project_number: 3M01RR002602-22S1
project_title: EVALUATION OF NOVEL TREATMENTS FOR STIMULANT DEPENDENCE
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5364
contact_pi_person_id: 1877426
contact_pi: WALSH, SHARON L
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.Cocaine abuse continues to pose a significant public health problem in the U.S. with no broadly effective treatment available.  Cocaine exerts a broad array of pharmacological effects but several decades of multidisciplinary research have led to the accepted theory that the mesolimbic-cortical dopamine system plays a critical role in mediating the reinforcing effects of cocaine related to its abuse.  Moreover documented neural perturbations in dopamine systems result from chronic cocaine use and are hypothesized to underlie the persistent craving and withdrawal symptoms that occur during abstinence.  Clinical studies evaluating dopamine agents have however failed to demonstrate efficacy against cocaine use; these results are attributable in part to the adverse effects associated with the clinically available dopamine agonists and traditional dopamine antagonists.  More recently it has been theorized that compounds with partial agonist/antagonist properties at dopamine receptor sites may provide an effective pharmacological strategy with a decreased risk of intolerable side effects.

Aripiprazole is the newest atypical antipsychotic marketed in the United States.  Its neuropharmacological profile distinguishes it from all other atypical antipsychotics.  Aripiprazole exhibits high affinity for the D2 receptor where it behaves as a partial agonist in contrast to the antagonist actions of other atypical antipsychotics.  Aripiprazole also acts as a partial agonist at the 5-HT1a and as an antagonist at 5-HT2 receptors.  These receptor systems are recognized as playing an important role in mood regulation and activity at these sites has been shown to modify the effects of cocaine in a variety of paradigms. The combined receptor actions coupled with its intermediate intrinsic efficacy have led to the characterization of aripiprazole as a new class of agent a dopamine-serotonin stabilizer.  We hypothesize that aripiprazole may be effective against cocaine use by direct blockade of its acute effects and through restoration of neural homeostasis of systems dysregulated by chronic cocaine use.  

Aripiprazole may also have therapeutic efficacy against cigarette smoking.  Clinical studies suggest that D2 receptor activity can modify smoking behavior in normal smokers.  Moreover studies in schizophrenics who smoke suggest that atypical antipsychotic agents may significantly reduce cigarette smoking in comparison to baseline rates when patients are maintained on traditional antipsychotics.  Together these intriguing data suggest that atypical antipsychotic medications with their combined dopamine and serotonin activities may be a useful strategy for reducing cigarette smoking.   The present inpatient study whose principal aim is to evaluate the efficacy of aripiprazole against cocaine provides a unique opportunity to explore the effects on smoking as a secondary aim.  

The primary aims of this project are to: 1) evaluate the safety and tolerability of aripiprazole over a range of doses in individuals who are cocaine and tobacco dependent
2) evaluate the ability of aripiprazole to attenuate the positive subjective effects of cocaine related to its abuse liability in comparison to placebo and 3) evaluate directly the efficacy of aripiprazole to reduce the reinforcing efficacy of cocaine by employing validated laboratory procedures of cocaine self-administration.  The secondary aims of this project are to:  1) evaluate the efficacy of aripiprazole over a range of doses to reduce cigarette smoking using controlled laboratory methodology of smoking topography and 2) evaluate the effect of aripiprazole on ad lib smoking in a controlled inpatient laboratory environment.

This project will enroll healthy cocaine-dependent volunteers who are cigarette smokers.  They will reside as inpatients under careful medication supervision for the study duration.   The study will employ a double-blind randomized parallel group multi-dose design to explore the effect of aripiprazole on cocaine and cigarette smoking outcomes.  The methods planned for use have been developed and successfully employed in our laboratory.  We hypothesize that aripiprazole treatment will significantly reduce the positive subjective response to cocaine and will significantly reduce cocaine self-administration in comparison to placebo.  We also hypothesize that significant reductions in smoking behavior will occur in response to aripiprazole treatment in comparison to placebo.  This project will provide important new information on the relative safety and efficacy of aripiprazole for the treatment of cocaine dependence and tobacco dependence while producing the requisite safety interaction data needed for the launch of an outpatient clinical trial to evaluate aripiprazole in outpatient cocaine dependent individuals.

project_terms:
Abstinence;Abuse Cocaine;Acute;Adverse effects;Affinity;Agonist;Antipsychotic Agents;Attenuated;Chronic;Cigarette Smoker;Class;Clinical Research;Clinical Trials;Cocaine;Computer Retrieval of Information on Scientific Projects Database;Coupled;Data;Dependence;Dependence Tobacco;Dopamine;Dopamine Agonists;Dopamine Antagonists;Dopamine D2 Receptor;Dopamine Receptor;Dopaminergic Agents;Dose;Double-Blind Method;Enrollment;Environment;Evaluation;Exhibits;Funding;Grant;Homeostasis;Individual;Inpatients;Institution;Laboratories;Laboratory Procedures;Marketing;Mediating;Methodology;Methods;Outcome;Outpatients;Patients;Pharmaceutical Preparations;Placebos;Play;Property;Psychostimulant dependence;Randomized;Range;Rate;Relative (related person);Research;Research Personnel;Resources;Risk;Role;Safety;Schizophrenia;Self Administration;Serotonin;Site;Smoke;Smoker;Smoking;Smoking Behavior;Source;Study Interdisciplinary;Supervision;System;Tobacco;Treatment Efficacy;United States;United States National Institutes of Health;Withdrawal Symptom;aripiprazole;atypical antipsychotic;cigarette smoking;craving;design;dopamine system;mood regulation;novel;public health medicine (field);receptor;relating to nervous system;response;restoration;theories;volunteer


application_id: 7607353
project_number: 3M01RR002602-22S1
project_title: NEUROIMAGING STUDIES OF DEPRESSION IN PARKINSON'S DISEASE
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5363
contact_pi_person_id: 8273960
contact_pi: BLONDER, LEE XENAKIS
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.Depression is a common and potentially serious complication of Parkinson's disease (PD). Studies show that approximately 40 percent of PD patients are depressed. There is evidence that these patients have deficits in verbal fluency set shifting confrontation naming and memory relative to non-depressed PD patients. Despite the widespread toll on emotional health posed by PD few studies have undertaken a comprehensive examination of the neural underpinnings of Parkinsonian depression. In this project we will compare depressed versus non-depressed Parkinson patients to a sample of demographically-matched healthy controls using neuropsychological assessment and magnetic resonance imaging (MRI). Our primary hypothesis is that depression in PD is linked to structural and functional abnormality in dorsal and ventral striatum amygdala orbitofrontal cortex medial frontal cortex and anterior cingulate.  Based on this we predict that in comparisons with non-depressed PD patients PD patients with depression will show 1.) significant reductions in the volume of the caudate nucleus orbitofrontal cortex medial frontal cortex anterior cingulate and amygdala; and 2.) reduced activation on cognitive and emotional tasks known to engage these regions.  Our secondary hypothesis is that anti-parkinsonian medications particularly D2/D3 receptor agonists will result in elevation in mood and increased activation in these brain regions among depressed PD patients during the performance of cognitive and emotional tasks.

To delineate the neural substrates of Parkinsonian depression each patient and control will undergo neuropsychological testing and structural and functional MRI.  We will compare regional brain volume in structures associated with depression and patterns of functional MRI activation during working memory and facial affect processing tasks. Neuropsychological testing and fMRI will be performed "on" and "off" dopaminergic pharmacotherapy in PD patients and at two similar time points in the unmedicated control group. The research proposed herein will contribute to our understanding of the neural pathways that underlie depression in PD the relationship of dysphoria to cerebral activation during cognitive and affective processing and the effects of dopaminergic pharmacotherapy on brain response in prefrontal and limbic regions.

project_terms:
Affect;Affective;Agonist;Amygdaloid structure;Anterior;Brain;Brain region;Caudate nucleus structure;Cerebrum;Cognitive;Complication;Computer Retrieval of Information on Scientific Projects Database;Control Groups;Depressed mood;Dorsal;Elevation;Emotional;Face;Funding;Grant;Health;Institution;Link;Magnetic Resonance Imaging;Magnetic Resonance Imaging Functional;Medial;Memory;Memory Short-Term;Mental Depression;Moods;Names;Neural Pathways;Neuropsychological Tests;Parkinson Disease;Parkinsonian Disorders;Patients;Pattern;Performance;Pharmaceutical Preparations;Pharmacotherapy;Process;Relative (related person);Research;Research Personnel;Resources;Sampling;Source;Striatum Ventral;Structure;Time;United States National Institutes of Health;base;brain volume;dysphoria;frontal lobe;neuroimaging;neuropsychological;receptor;relating to nervous system;response


application_id: 7607352
project_number: 3M01RR002602-22S1
project_title: GENETIC TESTING OF PLATELET GENES: PHASE I AND PHASE II
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5362
contact_pi_person_id: 10376252
contact_pi: OESTREICH, JULIE HEATHER
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The goal of this research protocol is to determine if polymorphisms in the P2Y12 and glycoprotein (GP) IIb/IIa receptor genes contribute to increased platelet expression of the P2Y12 receptor and subsequent platelet activation events. Inhibiting the P2Y12 receptor with clopidogrel is crucial for preventing major adverse cardiovascular events. Patient response to clopidogrel however are extremely variable and negative outcomes have been attributed to differences in drug effectiveness.

project_terms:
Blood Platelets;Cardiovascular system;Computer Retrieval of Information on Scientific Projects Database;Effectiveness;Event;Funding;Genes;Genetic screening method;Glycoproteins;Goals;Grant;Institution;Outcome;Patients;Pharmaceutical Preparations;Phase;Platelet Activation;Polymorphism Genetic;Protocols documentation;Receptor Gene;Research;Research Personnel;Resources;Source;United States National Institutes of Health;clopidogrel;prevent;receptor;response


application_id: 7607351
project_number: 3M01RR002602-22S1
project_title: RIM
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5361
contact_pi_person_id: 1888793
contact_pi: CROFFORD, LESLIE J
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.Rituximab is a genetically engineered chimeric murine/human monoclonal antibody. Directed against the CD20 antigen on B-cells. Promotes B-cell lysis down regulation apoptosis and down regulation.

project_terms:
Apoptosis;B-Lymphocytes;CD20 Antigens;Computer Retrieval of Information on Scientific Projects Database;Cytolysis;Down-Regulation;Engineering;Funding;Grant;Institution;Mus;Research;Research Personnel;Resources;Source;United States National Institutes of Health;human monoclonal antibodies;rituximab


application_id: 7607350
project_number: 3M01RR002602-22S1
project_title: MICRONEEDLE ASSISTED TRANSDERMAL DELIVERY OF NALTREXONE HYDROCHOLIDE
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5360
contact_pi_person_id: 6082060
contact_pi: WERMELING, DANIEL PAUL
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.Therapeutic utility of transdermal drug delivery is limited to medications exhibiting optimal physicochemical properties.  Innovative technical approaches have been studied to increase the opportunity of therapeutically important medications to be considered for transdermal delivery.  These approaches have included formulation chemistry as well as skin altering techniques of ionto- and sonophoresis electroporation and microneedles (MN).  A decade of in-vitro and animal MN delivery research has demonstrated MN technology can deliver small molecules proteins DNA and vaccines for systemic action.  However there are no in-vivo human experiments demonstrating clinically meaningful bioavailability of a medication whose transdermal delivery was enhanced by MN technology pretreatment of the skin.

The purpose of this study was to evaluate the pharmacokinetic parameters systemic side effects and local skin tolerance of MN-enhanced transdermal delivery of naltrexone hydrochloride (NTX) in healthy human volunteers.  

The hypotheses were:
1.after MN pretreatment of the skin therapeutic NTX plasma levels would be rapidly achieved and sustained for 72 hours of transdermal NTX patch application
2.control subjects would not demonstrate systemic NTX exposure after wearing a standard NTX patch with no MN pretreatment of the skin and 
3.MN pretreatment of the skin would be well tolerated and that there would be no clinically significant systemic or local toxicity.

project_terms:
Adverse effects;Animals;Biological Availability;Computer Retrieval of Information on Scientific Projects Database;Drug Kinetics;Electroporation;Exhibits;Formulations Drug;Funding;Grant;Hour;Human;In Vitro;Institution;Naltrexone;Naltrexone hydrochloride;Personal Satisfaction;Pharmaceutical Preparations;Plasma;Property;Proteins;Purpose;Research;Research Personnel;Resources;Science of Chemistry;Skin;Source;Standards of Weights and Measures;Techniques;Technology;Therapeutic;Toxic effect;Transdermal substance administration;United States National Institutes of Health;Vaccines DNA;Volunteers Human;clinically significant;in vivo;innovation;research study;small molecule


application_id: 7607349
project_number: 3M01RR002602-22S1
project_title: BEHAVIORAL EFFECTS ON DRUGS: INPATIENT (09)
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5359
contact_pi_person_id: 1888410
contact_pi: RUSH, CRAIG R
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.Cocaine abuse and dependence continue to be significant public health concerns. In 2003 over two million Americans had used cocaine in the past month. While this figure has not changed in recent years cocaine is still the most frequently mentioned drug in emergency-room admissions. The percentage of 12th- 10th- and 8th-graders that used cocaine in the past year as well as the percentage of treatment admissions involving cocaine has also remained stable in recent years. In Kentucky the location of the applicant institution the percentage of treatment admissions involving cocaine increased from 7.4% in 2002 to 9.4% in 2003. In 1996 cocaine use cost society over $45 billion due to medical consequences lost productivity and crime.

Because of the public-health concerns and costs associated with its abuse identifying a pharmacotherapy for the treatment of cocaine abuse is a priority with the National Institute on Drug Abuse (N.I.D.A.). Despite intense research efforts a pharmacological adjunct for cocaine dependence has not yet been identified.

Agonist replacement therapies are effective for nicotine and opioid dependence. The results of recently published preclinical studies and clinical trials suggest that agonist replacement therapies (e.g. d-amphetamine) may also be effective for cocaine dependence. To the best of our knowledge however there are no published laboratory studies with humans that demonstrated the efficacy of an agonist replacement therapy (e.g. d-amphetamine) for cocaine dependence. Consistent with the findings of preclinical studies and clinical trials that suggest d-amphetamine is effective in the management of stimulant dependence the results of an ongoing pilot study in our laboratory suggest that pretreating volunteers with d-amphetamine reduces subsequent d-amphetamine self-administration. Whether pretreating volunteers with d-amphetamine would reduce the self-administration of more widely abused stimulants like cocaine is unknown.
Importantly because d-amphetamine reduces cocaine use these clinical findings can now be used as a reference to identify appropriate human laboratory procedures for screening putative pharmacotherapies. Identifying and refining laboratory procedures for assessing the efficacy of putative pharmacotherapies is important because human laboratory studies can be conducted more rapidly and efficiently than clinical trials. 

The present project has two specific aims. The first specific aim is to demonstrate the sensitivity and predictive validity of human laboratory procedures commonly used to screen putative pharmacotherapies for cocaine dependence. To accomplish this aim we will conduct two "proof-of-concept" studies to determine the effects of cocaine during d-amphetamine maintenance. The initial experiment will demonstrate the safety and tolerability of d-amphetamine-cocaine combinations in non-treatment seeking individuals with recent histories of cocaine use (Exp. 1). Subjective-effect questionnaires will be used to characterize the behavioral effects of d-amphetamine-cocaine combinations. We will then determine the reinforcing effects of intranasal cocaine during d-amphetamine maintenance using a progressive-ratio procedure (Exp. 2). The ability to attenuate the reinforcing effects of cocaine may be an important characteristic of an effective pharmacotherapy for cocaine dependence. We chose to use a progressive-ratio schedule because it provides a quantitative assessment of the strength of a drug to maintain behavior. The results of preclinical studies suggest that chronic d-amphetamine treatment reduces cocaine self-administration under a progressive-ratio schedule. In the event that d-amphetamine does not attenuate the reinforcing effects of cocaine under the progressive-ratio schedule additional "proof-of-concept" experiments will be conducted using choice procedures before proceeding to the studies designed to accomplish the second specific aim.

The second specific aim is to determine the efficacy of atomoxetine (Strattera) as a putative agonist replacement pharmacotherapy for cocaine dependence. To accomplish this aim we will conduct two experiments to determine the effects of cocaine during atomoxetine maintenance. In Exp. 3 we will determine the safety and tolerability of atomoxetine-cocaine combinations. Finally we will determine whether chronic atomoxetine treatment attenuates the reinforcing effects of cocaine (Exp. 4). Atomoxetine a potent norepinephrine uptake blocker was chosen for study because its pharmacological and behavioral effects overlap to some extent with those of d-amphetamine. Importantly atomoxetine has less abuse potential than prototypical stimulants. An ideal agonist replacement therapy for stimulant dependence should produce some stimulant-like drug effects but have low abuse potential. We are unaware of any reports in which the effects of cocaine were assessed during atomoxetine maintenance. Identifying novel agonist replacement therapies is important because clinicians may be reluctant to use d-amphetamine because of its abuse potential.

project_terms:
Abuse Cocaine;Accident and Emergency department;Addiction Opiate;Admission activity;Agonist;American;Attenuated;Behavior;Behavioral;Characteristics;Chronic;Clinical;Clinical Trials;Cocaine;Computer Retrieval of Information on Scientific Projects Database;Crime;Dependence;Dependences Cocaine;Dextroamphetamine;Drug abuse;Event;Funding;Grant;Human;Individual;Inpatients;Institutes;Institution;Kentucky;Knowledge;Laboratories;Laboratory Procedures;Laboratory Study;Location;Maintenance;Medical;Nicotine;Norepinephrine;Pharmaceutical Preparations;Pharmacotherapy;Pilot Projects;Procedures;Productivity;Psychostimulant dependence;Publishing;Questionnaires;Recording of previous events;Replacement Therapy;Reporting;Research;Research Design;Research Personnel;Resources;Safety;Schedule;Self Administration;Societies;Source;Strattera;United States National Institutes of Health;atomoxetine;concept;cost;novel;preclinical study;public health medicine (field);research study;stimulant abuse;uptake;volunteer


application_id: 7607348
project_number: 3M01RR002602-22S1
project_title: BEHAVIORAL EFFECTS OF DRUGS (INPATIENT): 08
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5358
contact_pi_person_id: 1888410
contact_pi: RUSH, CRAIG R
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The primary hypothesis is that the aripiprazole-cocaine combinations will be well tolerated and no adverse effects will occur. Secondary hypotheses include: 1) intranasal cocaine will produce prototypical stimulant-like subjective effects (e.g. increased ratings Drug Liking); 2) aripiprazole will produce mild transient side effects observed with antipsychotics (e.g. sedation performance impairment); and 3) aripiprazole maintenance will attenuate the subjective effects of intranasal cocaine (i.e. shift the cocaine dose-response curve rightward).

project_terms:
Adverse effects;Antipsychotic Agents;Attenuated;Behavioral;Cocaine;Computer Retrieval of Information on Scientific Projects Database;Dose;Funding;Grant;Impairment;Inpatients;Institution;Maintenance;Performance;Personal Satisfaction;Pharmaceutical Preparations;Rate;Research;Research Personnel;Resources;Sedation procedure;Source;United States National Institutes of Health;aripiprazole;response


application_id: 7607347
project_number: 3M01RR002602-22S1
project_title: REDOX MODULATION OF MUSCLE FUNCTION IN MICROGRAVITY
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5357
contact_pi_person_id: 1869134
contact_pi: REID, MICHAEL B
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.Specific Aim: To evaluate NAC as a countermeasure for handgrip fatigue in humans.  N-acetylcysteine (NAC; reduced thiol donor) has been shown to inhibit human muscle fatigue in several recent studies.  Experiments in healthy volunteers will optimize the preparation and dosage of oral NAC administration and will test NAC effects on handgrip strength and handgrip fatigue during concentric exercise. Hypothesis 1. Oral NAC administration can increase blood thiol levels and inhibit exercise-induced oxidative stress without undesirable side effects.  Five NAC doses and two preparations solution or capsule will be tested to optimize glutathione protection and minimize side effects.  Hypothesis 2. NAC pretreatment delays task failure during concentric handgrip exercise.  The most effective NAC administration protocol from Expt. 1 will be tested for its capacity to delay fatigue during a standardized protocol of volitional handgrip exercise.

project_terms:
Acetylcysteine;Adverse effects;Blood;Computer Retrieval of Information on Scientific Projects Database;Dose;Exercise;Failure (biologic function);Fatigue;Funding;Glutathione;Grant;Human;Institution;Microgravity;Muscle Fatigue;Muscle function;Oral;Oxidation-Reduction;Oxidative Stress;Preparation;Protocols documentation;Research;Research Personnel;Resources;Solutions;Source;Sulfhydryl Compounds;Testing;United States National Institutes of Health;capsule (pharmacologic);dosage;healthy volunteer;research study


application_id: 7607346
project_number: 3M01RR002602-22S1
project_title: LINKING DEPRESSION WITH INCREASED MORBIDITY AND MORTALITY IN PATIENTS W HF
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5356
contact_pi_person_id: 1906318
contact_pi: MOSER, DEBRA KAY
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The purpose of this study is to explore these two potential mechanisms for the known association between depression and increased morbidity and mortality in Heart Failure (HF). The specfic aim for this study is to determine whether both Sympathetic nervous system (SNS) arousal and nonadherence contribute to the association between depression and poorer HF outcomes. This aim will be tested in a prospective correlational study in which the mediating effects of both DND arousal and nonadherence on the association between depression and the HF patient outcomes will be tested. A total of 300 patients with a confirmed diagnosis of chronic HF from an ischemic etiology with impaired left ventricular systolic function will be followed. Results of this study will provided vital information about the mechanisms linking depression and poor outcomes that clinicians and researchers can use in the design of effective interventions.

project_terms:
Arousal;Chronic;Computer Retrieval of Information on Scientific Projects Database;Diagnosis;Etiology;Funding;Grant;Heart failure;Institution;Intervention;Left;Link;Mediating;Mental Depression;Morbidity - disease rate;Mortality Vital Statistics;Outcome;Patients;Purpose;Research;Research Personnel;Resources;Source;Sympathetic Nervous System;Testing;United States National Institutes of Health;Ventricular;design;prospective


application_id: 7607345
project_number: 3M01RR002602-22S1
project_title: GESTATIONAL DIABETES MELLITUS: IMPACT ON ORAL HEALTH
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5355
contact_pi_person_id: 1880406
contact_pi: NOVAK, KAREN F.
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.General hypothesis is that women with GDM are at higher risk for developing more severe periodontal disease than women without GDM and that the combination of GDM and periodontal disease will be associated with an increased negative impact on maternal and fetal health. The following Specific Aims are designed to address this question. To Characterize the prevalence extent and severity of of periodonitis and associations between periodontits and adverse maternal and fetal outcomes in women who develop GDM compared to women who don't develop GDM. Aim 2 will characterize the subgingival microbial ecology in women with GDM and periodontal disease and determine if specific microbial characteristics are associated with adverse pregnancy and fetal outcomes. Aim 3 will determine if patients with GDM and periodontitis have elevated levels of circulating inflammatory mediators comaper to women with GDM and no periodonititis and the non-GDM controls.

project_terms:
Address;Characteristics;Computer Retrieval of Information on Scientific Projects Database;Diabetes Gestational;Ecology;Funding;Grant;Health;Inflammatory;Institution;Mediator of activation protein;Oral health;Outcome;Patients;Periodontal Diseases;Periodontitis;Pregnancy;Prevalence;Research;Research Personnel;Resources;Risk;Severities;Source;United States National Institutes of Health;Woman;design;fetal;microbial


application_id: 7607344
project_number: 3M01RR002602-22S1
project_title: JC VIRUS EXPRESSION IN THE OROPHARYNX AND HIV
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5354
contact_pi_person_id: 8534501
contact_pi: BERGER, JOSEPH R
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.This study is an exploratory analysis of the difference in the prevalence of the JC Virus in oropharyngeal secretions and blood of healthy individuals persons with Acquired Immune Deficiency Syndroms (AIDS) and pes with progressive multifocal leukoencephalopathy (PML). Saliva and throat washings as well as whole blood samples will be taken from each group. Saliva samples and throat washings will be analyzed for JCV using polymerase chain reaction (PCR). Whole blood samples will be collected and analyzed for JCV using PCR and for the presence of JCV in peripheral blood leukocytes (PBLs) using CD4 lymphocyte counts. These measures will be used to determine whether JCV is harbored in the oropharynx whether a correlation exists between JCV levels in the oropharynx and those in PBLs and to determine whether the level and strain of JCV shed from the oropharynx correlates with the degree of immunosuppression. It is predicted that JCV will be present in oropharyngeal fluids the frequency of detection of JCV will be increased in patients with AIDS-associated PML compared with healthy controls and HIV-seropositive patients without PML and that higher levels of the JC Virus will correlate with increased immunosuppression.

project_terms:
Acquired Immunodeficiency Syndrome;Blood;Blood specimen;CD4 Lymphocyte Count;Computer Retrieval of Information on Scientific Projects Database;Detection;Frequencies (time pattern);Funding;Grant;Individual;Institution;JC Virus;Leukocytes;Leukoencephalopathy Progressive Multifocal;Liquid substance;Measures;Natural immunosuppression;Oropharyngeal;Patients;Persons;Pes;Pharyngeal structure;Polymerase Chain Reaction;Prevalence;Research;Research Personnel;Resources;Saliva;Sampling;Source;Therapeutic immunosuppression;United States National Institutes of Health;Virus;Whole Blood;peripheral blood


application_id: 7607343
project_number: 3M01RR002602-22S1
project_title: BIOBEHAVIORAL INTERVENTION IN HEART FAILURE
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5353
contact_pi_person_id: 1906318
contact_pi: MOSER, DEBRA KAY
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The purpose of this study is to find out if relaxation training can produce beneficial changes in the psychological and physical health status of patients with heart failure.

project_terms:
Computer Retrieval of Information on Scientific Projects Database;Funding;Grant;Health Status;Heart failure;Institution;Intervention;Patients;Purpose;Relaxation Therapy;Research;Research Personnel;Resources;Source;United States National Institutes of Health;biobehavior;psychologic


application_id: 7607342
project_number: 3M01RR002602-22S1
project_title: SELENIUM AND VITAMIN E CANCER PREVENTION TRIAL (SELECT)
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5352
contact_pi_person_id: 8168805
contact_pi: ROWLAND, RANDALL
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The primary objective is to assess the effect of selenium and vitamin E alone and in combination on the clinical incidence of prostate cancer. A secondary objective is to assess the effect of selenium and vitamin E alone and in combination on the incidence of other cancers including lung cancer colorectal cancer and all cancers combined. Another secondary objective is to assess the effect of selenium and vitamin E alone and in combination on the following measures: prostate cancer free survival lung cancer free survival colorectal cancer free survival cancer free survival overall survival and serious cardiovascular events.

project_terms:
Cancer Prevention Trial;Cardiovascular system;Clinical;Colorectal Cancer;Computer Retrieval of Information on Scientific Projects Database;Event;Funding;Grant;Incidence;Institution;Malignant Neoplasms;Malignant neoplasm of lung;Malignant neoplasm of prostate;Measures;Research;Research Personnel;Resources;Selenium;Selenium/vitamin E;Source;United States National Institutes of Health;Vitamins


application_id: 7607341
project_number: 3M01RR002602-22S1
project_title: WARCEF: WARFARIN VERSUS ASPIRIN IN REDUCED CARDIAC EJECTION FRACTION
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5351
contact_pi_person_id: 1859648
contact_pi: PETTIGREW, L. CREED
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The primary specfic aim of this randomized double-blind multi-center clinical trial is to determine whether warfarin (International Normalized Ratio [INR] 2.5-3.0 target INR 2.75) or aspirin (325 mg per day) is superior for preventing all-cause mortality and stroke combined in patients with ejection fraction (EF) great than or equal to 30% when balanced against any risk of intracerebral hemorrhage. The secondary aim is to answer the following questions: (1) Is warfarin or aspirin superior for reducing stroke alone? (2) Among women is warfarin or aspirin therapy superior for reducing all-cause mortality stroke and MI combined when balanced against any increased risk of intracerebral hemorrhage? (3) Among African-Americans is warfarin or aspirin therapy superior for reducing all-cause mortality stroke and MI combined when balanced against any increased risk of intracerebral hemorrhage? (4) Does any relative risk of benefit of warfarin or aspirin for stroke TIA or periheral embolism depend on ejection fraction? (5) Does any relative risk or benefit of warfarin or aspirin depend on the heart failure class (NYHA class)? (6) Does any relative risk or benefit of warfarin or aspirin depend on etiology of cardiac failure? (7) Do warfarin and aspirin differ in their effect on cognitive function? (8) Does warfarin have a larger risk reduction relative to aspirin in cardioembolic than other stroke subtyped? (9) Are cardioembolic infarcts more frequent in patients with non-ischemic than ischemic caridiac diseases? (10) Are cardioembolic infarcts more frequent in women than in men? (11) Is mean cerebral infarct volume greater in patients with EF less than or equal to 20% than in patients with EF greater than 20%? 
A tertiary aim is to combine our data with that of the Warfarin Antiplatelet Trial in Chronic Heart Failure (WATCH) to provide more statistical power to address the secondary aims 1 through 6.

project_terms:
Address;African American;Aspirin;Benefits and Risks;Cardiac;Cerebral hemisphere hemorrhage;Cerebrum;Chronic;Class;Computer Retrieval of Information on Scientific Projects Database;Data;Disease;Double-Blind Method;EFRAC;Embolism;Equilibrium;Etiology;Funding;Grant;Heart failure;Infarction;Institution;International Normalized Ratio;Mortality Vital Statistics;Multi-Institutional Clinical Trial;Patients;Randomized;Relative (related person);Research;Research Personnel;Resources;Risk;Risk Reduction;Risks Relative;Source;United States National Institutes of Health;Warfarin;Woman;cognitive function;day;men;prevent;stroke


application_id: 7607340
project_number: 3M01RR002602-22S1
project_title: TRANSPORT GENE EXPRESSION AND DRUG ACCUMULATION IN MILK
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5350
contact_pi_person_id: 3149046
contact_pi: MCNAMARA, PATRICK J
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The goal of the protocol is to systematically evaluate the role of genes in the accumulation of drugs into human milk. By identifying which transporters are present in mammary epithelial cells we hope to establish not only the identity of transporters for nitrofurantoin and cimetidine but to focus future studies on those classes of drugs likely to accumulate into milk. Functional studies will substantiate the role of these expressed transporters in the specific accumulation of nitrofurantoin and cimetidine. The further development of a model cell system that mimics the human mammary epithelial cell barrier will significantly enhance our understanding of the mechanisms of drug transport into milk.

project_terms:
Cell model;Cimetidine;Class;Computer Retrieval of Information on Scientific Projects Database;Development;Drug Transport;Epithelial Cells;Funding;Future;Gene Expression;Genes;Goals;Grant;Human;Institution;Mammary gland;Milk;Milk Human;Nitrofurantoin;Pharmaceutical Preparations;Protocols documentation;Research;Research Personnel;Resources;Role;Source;System;United States National Institutes of Health


application_id: 7607339
project_number: 3M01RR002602-22S1
project_title: BIOCHEMICAL MORPHOLOGICAL AND TRACE ELEMENT STUDIES IN ALZHEIMER'S DISESAE
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5349
contact_pi_person_id: 1894359
contact_pi: MARKESBERY, WILLIAM R
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The objective of the Alzheimer's Disease Research Center Clinical Core is to provide clinical data study participants and the means of obtaining autopsy materials for research. It is designed to aid research on current central scientific questions in AD and related diseases. The clinical core does not address these questions directly but makes available a group of well-characterized subjects to enable substantive research on these important current questions. To do this the clinical core 1) follows a group of community-dwelling normal elderly individuals to autopsy 2) follows an existing group of individuals with dementia to autopsy 3) evaluates and diagnoses individuals with memory disorders and 4) adds to the registry of individuals who are potential participants in research studies.

project_terms:
Address;Alzheimer's Disease;Autopsy;Biochemical;Clinical;Clinical Data;Communities;Computer Retrieval of Information on Scientific Projects Database;Dementia;Diagnosis;Disease;Elderly;Funding;Grant;Individual;Institution;Memory Disorders;Participant;Registries;Research;Research Personnel;Resources;Source;Trace Elements;United States National Institutes of Health;design;research study


application_id: 7607338
project_number: 3M01RR002602-22S1
project_title: RENAL BONE DISEASE
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5348
contact_pi_person_id: 7875292
contact_pi: MALLUCHE, HARTMUT H
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.Circulating levels of the "intact" parathyroid hormone (PTH) poorly reflect the level of bone turnover in patients with end-stage renal disease (ESRD).  Because low and high turnover bone diseases in ESRD have opposite therapeutic implications it is essential to refine noninvasive diagnostic tools for assessment of bone turnover.  The long-term goal is to understand regulation of bone turnover in patients with ESRD.

project_terms:
Bone Diseases;Computer Retrieval of Information on Scientific Projects Database;Diagnostic;End stage renal failure;Funding;Goals;Grant;Institution;Kidney;PTH protein human;Parathyroid Hormones;Patients;Regulation;Research;Research Personnel;Resources;Source;Therapeutic;United States National Institutes of Health;bone turnover;tool


application_id: 7607337
project_number: 3M01RR002602-22S1
project_title: LEPTIN ANOREXIA AND WEIGHT LOSS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5347
contact_pi_person_id: 8535399
contact_pi: GAETKE, LISA M
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The purpose of this study is to determine possible etiologies for decreased food intake and weight loss in inflammatory bowel disease patients. Anorexia is a major complication of inflammatory bowel disease (IBD). The objective of this research is to investigate the relationship between inflammation and leptin/ghrelin dysregulation. The hypothesis is that anorexia and weight loss in inflammatory bowel disease (IBD) are regulated by inappropriately elevated leptin or reduced ghrelin concentration for body weight and fat mass. Leptin a cytokine hormone secreted by the adipocyte and the recently described ghrelin produced predominately by the gastric mucosa play a central role in food intake and energy balance. It has been suggested that inflammation and infection along with the consequent increased release of inflammatory mediators particularly the proinflammatory cytokines interleukin-1 (IL-1) tumor necrosis factor- alpha (TNF-alpha) and interleukin-6 (IL-6) maintain serum leptin concentration at an inappropriately elevated or normal fed state resulting in no physiological need or desire for food intake. The precise control of ghrelin secretion remains uncertain. It has been suggested that leptin concentrations directly influence ghrelin secretion but it is also possible that inflammatory mediators may affect leptin and/or ghrelin concentrations.The specific aims of this proposal are: 1) to determine whether serum leptin and ghrelin concentrations in Crohns Disease (CD) patients (ages 12 to 35 yrs) who have had weight loss and are below normal weight for height differ from CD patients who have not had weight loss and are within 10% of their ideal body weight and healthy controls within 10% of their ideal body weight in both the fed and fasted state 2) to examine the acute phase response and determine whether it correlates with abnormal leptin and ghrelin responses and weight loss and 3) to determine whether body composition particularly fat mass and metabolic rate correlate with leptin and ghrelin responses weight loss and CD activity.

project_terms:
Acute-Phase Reaction;Adipocytes;Affect;Age;Anorexia;Body Composition;Body Weight;Body Weight decreased;Complication;Computer Retrieval of Information on Scientific Projects Database;Desire for food;Disease;Eating;Etiology;Fasting;Fatty acid glycerol esters;Funding;Gastric mucosa;Grant;Height;Hormones;Infection;Inflammation;Inflammatory;Inflammatory Bowel Diseases;Institution;Interleukin-1;Interleukin-6;Leptin;Mediator of activation protein;Metabolic;Patients;Physiological;Play;Purpose;Rate;Research;Research Personnel;Resources;Role;Serum;Source;TNF protein human;Tumor Necrosis Factor-alpha;United States National Institutes of Health;Weight;cytokine;energy balance;feeding;ghrelin;response


application_id: 7607336
project_number: 3M01RR002602-22S1
project_title: INFLAMMATORY MEDIATOR LEVELS IN PATIENTS WITH ADVANCED PERIODONTAL DISEASE
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5346
contact_pi_person_id: 2045756
contact_pi: CUNNINGHAM, LARRY L
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.Periodontal disease and dental caries are ubiquitous in the population. Recent literature has linked oral inflammatory conditions to elevations in circulating inflammatory mediators. In addition inflammatory mediators such as C-reactive protein have been linked to cardiovascular disease and a reduction of CRP has been shown to decrease the risk of MI and Stroke. The investigators propose to evaluate the levels of three inflammatory mediators CRP IL-6 and fibrinogen in patients with periodontal disease and dental caries who are having all their teeth removed prior to denture construction. They plan to follow these patients for one year with periodic re-evaluations with venipuncture to establish whether or not there is a decrease in these inflammatory mediators after elimination of oral disease.

project_terms:
C-reactive protein;Cardiovascular Diseases;Computer Retrieval of Information on Scientific Projects Database;Condition;Dental caries;Dentures;Elevation;Evaluation;Facility Construction Funding Category;Fibrinogen;Funding;Grant;Inflammatory;Institution;Interleukin-6;Link;Literature;Mediator of activation protein;Mouth Diseases;Oral;Patients;Periodontal Diseases;Population;Research;Research Personnel;Resources;Risk;Source;Tooth structure;United States National Institutes of Health;Venipunctures;cysteine rich protein;stroke


application_id: 7607335
project_number: 3M01RR002602-22S1
project_title: ULTRASE MT20
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5345
contact_pi_person_id: 9033977
contact_pi: KANGA, JAMSHED F
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The proposed clinical study will be conducted to demonstrate the clinical efficacy and to investigate the safety of ULTRASE MT20 formulation in CF patients with pancreatic insufficiency.

project_terms:
Clinical Research;Computer Retrieval of Information on Scientific Projects Database;Exocrine pancreatic insufficiency;Formulations Drug;Funding;Grant;Institution;Research;Research Personnel;Resources;Safety;Source;United States National Institutes of Health;clinical efficacy;cystic fibrosis patients


application_id: 7607334
project_number: 3M01RR002602-22S1
project_title: LICIT AND ILLICIT OPIOIDS: COMPARATIVE STUDIES IN HUMANS: STUDY 1
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5344
contact_pi_person_id: 1877426
contact_pi: WALSH, SHARON L
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.To characterize the pharmacodynamic properties of oral oxycodone across a full range of doses in sporadic opioid abusers. To characterize the pharmacodynamic properties of oral hyrocodone across a full range of doses in sporadic opioid abusers. To characterize the relative abuse potential of oxycodone and hydrocodone in the population by comparing it to hydromorphone an opioid of know high abuse potential and placebo. We hypothesis that all three drugs will produce a subjective profile associated with abuse liability. There will be a disassociation between the physiological potency of these drugs and their abuse liability profile. Doses producing physiologically equivaltent effects the relative potency for producing subjective effects related to abuse liabiilty differ in magnitude whereby hydromorphone> oxycodone> hydrocodone.

project_terms:
Comparative Study;Computer Retrieval of Information on Scientific Projects Database;Dose;Funding;Grant;Hydrocodone;Hydromorphone;Institution;Opioid;Oral;Oxycodone;Pharmaceutical Preparations;Pharmacodynamics;Physiological;Placebos;Population;Property;Range;Relative (related person);Research;Research Personnel;Resources;Source;United States National Institutes of Health;human study


application_id: 7607333
project_number: 3M01RR002602-22S1
project_title: UNIVERSITY OF KENTUCKY LABORATORY OF HUMAN BEHAVIORAL PHARMACOLOGY SCREENING
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5343
contact_pi_person_id: 1888410
contact_pi: RUSH, CRAIG R
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The University of Kentucky Laboratory of Human Behavioral Pharmacology (UK LHBP) is currently funded by NIH to conduct drug abuse research in humans. Prior to participating in this research volunteers must first be screened to determine wehterh they are eligible to participate. The purpose of this present protocol is to screen volunteers prior to participation in experiments at the UK LHBP.

project_terms:
Computer Retrieval of Information on Scientific Projects Database;Drug abuse;Funding;Grant;Human;Institution;Kentucky;Laboratories;Protocols documentation;Purpose;Research;Research Personnel;Resources;Screening procedure;Source;United States National Institutes of Health;Universities;behavioral pharmacology;research study;volunteer


application_id: 7607332
project_number: 3M01RR002602-22S1
project_title: ECTOPIC LIPIDS IN CHROHN'S DISEASE
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5342
contact_pi_person_id: 3087686
contact_pi: LUU, LAN C
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The auto-immune and immune medicated pathologies of Crohn's Disease (CD) highlight the similarities it shares with Acquired Immunodeficiency Syndrome (AIDS) from the human immunodeficiency virus (HIV) specifically in the areas of pathophysiologies anthropometric alterations and metabolic abnormalities. Aims: Utilize proton magnetic resonance spectroscopy imaging to measure and to compare the levels of IMCL and IHL in active CD states to iactive CD states and both to health controls. Link the levels of IMCL and IHL to levels of inflammatory factors adipokines and ROS in active and inactive CD states compared to healthy controls. Determine the relationship between the levels of IMCL and IHL to resting quotient and energt expenditure using indirect calorimetry (IC) and doubly labeled water; to body composition using dual energy x-ray absorptiometry (DXA); and fasting plasma glucose levels as determined by an oral glucose tolerance test (OGTT). Model a metabolic profile of IMCL IHL and energy metabolism in Crohn's subjects to estimate appropriate sample size requirements for larger scale studies.

project_terms:
Acquired Immunodeficiency Syndrome;Area;Body Composition;Calorimetry Indirect;Computer Retrieval of Information on Scientific Projects Database;Crohn's disease;Disease;Energy Metabolism;Expenditure;Fasting;Functional disorder;Funding;Glucose;Grant;HIV;Health;Image;Immune;Inflammatory;Institution;Label;Link;Lipids;Magnetic Resonance Spectroscopy;Measures;Metabolic;Modeling;OGTT;Pathology;Plasma;Protons;Research;Research Personnel;Resources;Rest;Sample Size;Source;United States National Institutes of Health;Water;adipokines


application_id: 7607331
project_number: 3M01RR002602-22S1
project_title: BEHAVORIAL EFFECTS OF DRUGS (INPATIENT): 06
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5341
contact_pi_person_id: 1888410
contact_pi: RUSH, CRAIG R
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The primary hypothesis is that the atomoxetine-cocaine combinations will be well tolerated and no adverse effects will occur. Secondary hypotheses include: 1) intranasal cocaine will produce prototypical stimulant-like subjective effects (e.g. increased ratings Drug Liking); 2) the two cocaine dose-response curves determined under placebo-maintenance conditions will not differ; 3) atomoxetine will produce mild transient side effects observed with stimulants (e.g. increased heart rate and blood pressure decreased appetite); and 4) atomoxetine maintenance will dose dependently attenuate the subjective effects of intranasal cocaine (i.e. shift the cocaine dose-response curve rightward).

project_terms:
Adverse effects;Attenuated;Blood Pressure;Cocaine;Computer Retrieval of Information on Scientific Projects Database;Condition;Desire for food;Dose;Funding;Grant;Heart Rate;Inpatients;Institution;Maintenance;Personal Satisfaction;Pharmaceutical Preparations;Placebos;Rate;Research;Research Personnel;Resources;Source;United States National Institutes of Health;atomoxetine;response


application_id: 7607330
project_number: 3M01RR002602-22S1
project_title: A PHARMACOLOGICAL ANALYSIS OF THC IN HUMANS (01)
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5340
contact_pi_person_id: 8046705
contact_pi: LILE, JOSHUA ANTHONY
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.To establish oral THC as a discriminative stimulus and characterize its effects on behavior and cognition. It is hypothesized that THC will function as a discriminative stimulus and produce other effects typically seen following cannabis administration. To determine if the effects of oral THC in humans can also be attributed to indirect involvement of the opioid GABA and DA systems. It is hypothesized that the opioid agonist hydromorphone and GABA modulator triazolam will partially substitue for THC and will have similar effects to THC on most expermental measures. In contrast it is hypothesized that the indirect DA agonist methylphenidate will not share discriminative-stimulus effects with THC and will have opposite effects on most experimental measures.

project_terms:
Agonist;Behavior;Cannabis;Cognition;Computer Retrieval of Information on Scientific Projects Database;Funding;GABA Modulators;Grant;Human;Hydromorphone;Institution;Measures;Methylphenidate;Opioid;Oral;Research;Research Personnel;Resources;Source;Stimulus;System;Triazolam;United States National Institutes of Health;gamma-Aminobutyric Acid


application_id: 7607329
project_number: 3M01RR002602-22S1
project_title: DIFFERENCES IN OPIOID-INDUCED HYPERALGESIA AND ANALGESIA
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5339
contact_pi_person_id: 6878921
contact_pi: HOLTMAN, JOSEPH R
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.Determine if low dose (subanalgesic) morphine produces an enhancement of pain sensitivity (hyeralgesia) in male and female subjects. Determine if the magnitude of the hyperalgesia is related to gender.

project_terms:
Absence of pain sensation;Analgesics;Computer Retrieval of Information on Scientific Projects Database;Dose;Female;Funding;Gender;Grant;Hyperalgesia;Institution;Morphine;Opioid;Pain;Research;Research Personnel;Resources;Source;United States National Institutes of Health;male


application_id: 7607328
project_number: 3M01RR002602-22S1
project_title: ALZHEIMER'S DISEASE NEUROIMAGING INITIATIVE (ADNI)
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5338
contact_pi_person_id: 1958116
contact_pi: SMITH, CHARLES K
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The overall goals of the Alzheimer's Disease Neuroimaging Initative Clinical Protocol will be to recruit 800 subjects and carry out all clinical evaluations including: neuropsychological and clinical assessments imaging studies and collection of biomarker.

project_terms:
Alzheimer's Disease;Biological Markers;Clinical Protocols;Clinical assessments;Collection;Computer Retrieval of Information on Scientific Projects Database;Funding;Goals;Grant;Image;Institution;Recruitment Activity;Research;Research Personnel;Resources;Source;United States National Institutes of Health;neuroimaging;neuropsychological;research clinical testing


application_id: 7607327
project_number: 3M01RR002602-22S1
project_title: COMPARISON BETWEEN TWO DIFFERENT CLOPIDOGREL MAINTENANCE DOSES
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5337
contact_pi_person_id: 1878190
contact_pi: HOLT, JOHN A
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.Increasing the maintenance dose of clopidogrel following a percutaneous intervention will result in increased suppression of platelet aggregation. The main goal of this study is to test whether an increase of the maintenance dose of clopidogrel from 75 to 150 mg per day results in an additional suppresion of ADP-induced platelet aggregation.

project_terms:
Computer Retrieval of Information on Scientific Projects Database;Dose;Funding;Goals;Grant;Institution;Intervention;Maintenance;Platelet aggregation;Research;Research Personnel;Resources;Source;Testing;United States National Institutes of Health;clopidogrel;day


application_id: 7607326
project_number: 3M01RR002602-22S1
project_title: MINERALOCORTICOID RECEPTOR ANTAGONISM IN PATIENTS WITH ACS
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5336
contact_pi_person_id: 9342361
contact_pi: BHATHEJA, ROHIT
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.We hypothesis that eplerenone improves endothelial function reduces inflammation and the prothrombotic milieu in patients with acute coronary syndromes (ACS). Aim 1: To determine the effects of mineralocorticoid receptor (MR) antagonism on various indices of oxidative stress in patients with ACS. Obtain levels of G6PD in red blood cells and monocytes; NADPH and glutathione. Aim 2: To assess the effects of MR blockade on platelet activation in ACS. Evaluate the effect on the following activeation-dependent platelet antigen P-selection (CD62) expression platelet monocyte aggregates and plasma soluble CD40 ligand levels. Aim 3: To evaluate the effects of MR antagonism on inflammation in ACS by measuring the following markers of vascular inflammation high sensitivity CRP (hs-CRP) pregnancy-associated plasma protein A (PAPP-A) monocyte-chemoattractant protein (MCP-1) interleukin (IL)-6 serum amyloid A (SAA) and myeloperoxidase (MPO).

project_terms:
Antigens;Blood Platelets;CCL2 gene;CD40 Ligand;Computer Retrieval of Information on Scientific Projects Database;Erythrocytes;Funding;G6PD gene;Glucosephosphate Dehydrogenase;Glutathione;Grant;Inflammation;Institution;Interleukin-6;Measures;Mineralocorticoid Receptor;Monocyte Chemoattractant Proteins;NADP;Oxidative Stress;Patients;Peroxidase;Plasma;Platelet Activation;Pregnancy-Associated Plasma Protein-A;Research;Research Personnel;Resources;SELP gene;Serum amyloid A protein;Source;United States National Institutes of Health;acute coronary syndrome;cysteine rich protein;eplerenone;improved;indexing;monocyte;vascular inflammation


application_id: 7607325
project_number: 3M01RR002602-22S1
project_title: NUTRITIONAL INTAKE AND PROINFLAMMATORY CYTOKINE ACTIVITY IN COMMUNITY DWELLING S
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5335
contact_pi_person_id: 1906096
contact_pi: LENNIE, TERRY A
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.Proinflammatory cytokines are elevated in people with chronic illness and in healthy older adults. Whether these cytokines have the same negative effect on nutrient intake in healthy adults as in chronic illness is unknown. The purpose of the proposed research is to examine the relationships between nutritional intake and proinflammatory cytokine activity in a group of healthy older adults. Forty community-dwelling adults aged 65 years or older and free of chronic illness will be recruited for the study. Nutritional intake will be assessed using four-day food diaries. Blood will be drawn and serum analyzed for TNF? soluble TNF receptors sTNFR1 and sTNFR2 IL-1ra IL-2 IL-4 IL-6 IL-8 IL-10 endotoxin albumin CRP uric acid and lipid panel. A 24-hour urine will be collected and analyzed for sodium and nitrogen. A descriptive examination of total number of nutrient deficiencies per person will be used to describe the nutritional intake of the group. The interaction among inflammatory markers and nutrtional intake will be determined by comparing calorie intake protein intake and number of nutritional deficiencies between two groups divided by a median split of serum cytokine levels. The effect of dietary fatty acid intake on proinflammatory cytokine activity will be determine by comparing proinflammatory cytokine levels between two groups divided by median intake of three fatty acids. This study will provide  data for comparison with our heart failure patients with respect to the effects of fatty acids on cytokine activity and whether cytokines are invovled in both the decrease in food intake associated with normal aging and heart failure. This information will assist in developing appropriate interventions to improve and maintain nutritional intake of older adults according to their health status.

project_terms:
Adult;Albumins;Blood;Chronic Disease;Communities;Computer Retrieval of Information on Scientific Projects Database;Data;Diet Records;Dietary Fatty Acid;Eating;Elderly;Endotoxins;Fatty Acids;Funding;Grant;Health Status;Heart failure;Hour;IL8 gene;Inflammatory;Institution;Intake;Interleukin-10;Interleukin-4;Interleukin-6;Intervention;Lipids;Malnutrition;Nitrogen;Numbers;Nutrient;Nutritional;Patients;Persons;Proteins;Purpose;Recruitment Activity;Research;Research Personnel;Resources;Serum;Sodium;Source;TNF gene;Tumor Necrosis Factor Receptor;United States National Institutes of Health;Uric Acid;Urine;aged;anakinra;cysteine rich protein;cytokine;day;improved;normal aging


application_id: 7607324
project_number: 3M01RR002602-22S1
project_title: PHASE III TRIAL OF MINOCYCLINE IN AMYOTROPHIC LATERAL SCLEROSIS
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5334
contact_pi_person_id: 1975664
contact_pi: KASARSKIS, EDWARD JOSEPH
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The hypothesis we will test in th current study is that minocycline slows the progessive deterioration of global function in patients with ALS. The primary outcome measure is change in the function as detected by the ALS Functional Rating Scale in patients taking minocycline compared to those taking placebo. The stuyd is 80% powered to detect A 15% or greater reduction in the average slope of patients' ALSFRS-R scores over time. The secondary outcome measures are changes in manual muscle testing (MMT) forced vital capacity (FVC percent predicted) and survival.

project_terms:
Am 80;Amyotrophic Lateral Sclerosis;Computer Retrieval of Information on Scientific Projects Database;Deterioration;Funding;Grant;Institution;Manuals;Minocycline;Muscle;Outcome Measure;Patients;Phase;Placebos;Rate;Research;Research Personnel;Resources;Score;Source;Testing;Time;United States National Institutes of Health;Vital capacity


application_id: 7607323
project_number: 3M01RR002602-22S1
project_title: PROJECT 5: ORAL INFECTIONS: DIETARY REGULATION OF LOCAL AND SYSTEMIC
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5333
contact_pi_person_id: 8263389
contact_pi: DAWSON, DOLPH R.
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.Periodontal disease is a chronic inflammatory condition that may have a significant negative impact on systemic conditions such as diabetes and cardiovascular disease and may increase the incidence of preterm birth in pregnant women. Preliminary studies have suggested that controlling oral infection and inflammation may have beneficial systemic effects.

project_terms:
Cardiovascular Diseases;Chronic;Computer Retrieval of Information on Scientific Projects Database;Condition;Diabetes Mellitus;Funding;Grant;Incidence;Inflammation;Inflammatory;Institution;Periodontal Diseases;Pregnant Women;Premature Birth;Regulation;Research;Research Personnel;Resources;Source;United States National Institutes of Health;oral infection


application_id: 7607322
project_number: 3M01RR002602-22S1
project_title: TRIALNET NATURAL HISTORY STUDY OF TYPE I DIABETES
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5332
contact_pi_person_id: 1945934
contact_pi: KAROUNOS, DENNIS G
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The overall objective of this study is to perform baseline and repeat assessments over time of the metabolic and immunologic status of individuals at risk for T1D in order to: Characterize their risk for developing T1D; Describe the pathogenetic evolution of T1D; and Increase the understanding of the pathogenetic factors involved in the development of T1D.

project_terms:
Computer Retrieval of Information on Scientific Projects Database;Development;Diabetes Mellitus;Diabetes Mellitus Insulin-Dependent;Evolution;Funding;Grant;Immunologics;Individual;Institution;Metabolic;Natural History;Research;Research Design;Research Personnel;Resources;Risk;Source;Time;United States National Institutes of Health


application_id: 7607321
project_number: 3M01RR002602-22S1
project_title: LEVOFLOXACIN PHARMACOKINETICS IN THE OBESE
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5331
contact_pi_person_id: 8855520
contact_pi: MOREHEAD, RICHARD
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The objectives of this study is to describe the pharmacokinetics of levofloxacin 750mg in ambulatory obese volunteers and in hospitalized obese patients. The pharmacokinetics of a 750mg intravenous does of levofloxacin administered to severly obese volunteers will not differ significantly from that of obese hospitalized medical patients. Determine the following pharmacokinetic parameters of levofloxacin in ovese individuals: Cmax Tmax area under the concentration-time curve (AUC) volume of distribution elimination rate serum half-life and urine clearance. Investigate the correlation between levofloxacin volume of distribution and actual adipose mass as determined by the whole body potassium counter in ambulatory volunteers.

project_terms:
Adipose tissue;Area;Computer Retrieval of Information on Scientific Projects Database;Drug Kinetics;Funding;Grant;Half-Life;Individual;Institution;Intravenous;Medical;Obesity;Ofloxacin (S)-Isomer;Patients;Potassium;Rate;Research;Research Personnel;Resources;Serum;Source;Time;United States National Institutes of Health;Urine;volunteer


application_id: 7607320
project_number: 3M01RR002602-22S1
project_title: BMI NUTRITION INFLAMMATION AND HEART FAILURE OUTCOMES "AGAF"
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5330
contact_pi_person_id: 1906096
contact_pi: LENNIE, TERRY A
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The purpose of the proposed research is to examine the relationships among body fat content nutritional intake inflammation and event-free survival in patients with heart failure (HF) of ischemic origin. Overweight and obese patients will have better event-free survival than normal and underweight patients regardless of number of nutrient deficiencies.

project_terms:
Body fat;Computer Retrieval of Information on Scientific Projects Database;Disease-Free Survival;Funding;Grant;Heart failure;Inflammation;Institution;Intake;Numbers;Nutrient;Nutritional;Obesity;Outcome;Overweight;Patients;Purpose;Research;Research Personnel;Resources;Science of nutrition;Source;Underweight;United States National Institutes of Health


application_id: 7607319
project_number: 3M01RR002602-22S1
project_title: ALZHEIMER'S DISEASE RESEARCH CENTER AD PATIENTS
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5329
contact_pi_person_id: 1958116
contact_pi: SMITH, CHARLES K
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The overall goal of the Clinical Core of The University of Kentucky Alzheimer's Disease Research Center (UK ADRC) is to support the research mission of the ADRC and provide excellent clinical diagnoses and care for patients with Alzheimer's disease (AD) and non-AD dementing disorders.  It will: (1) maintain a normal control (BRAiNS clinic) of 500 initially normal aged subjects who will be followed longitudinally to autopsy.  Emphasis will be on normal aging and transition to Mild Cognitive Impairment (MCI) and early AD; (2) maintain a Research Clinic of 200 subjects with probable AD and other non-AD dementias who will be followed longitudinally to autopsy; and (3) establish a group of 100 initially normal rural Appalachian aged subjects followed longitudinally to autopsy in the Berea Rural Appalachian Satellite Clinic for comparison to the urban based BRAiNS Clinic.  The control participants are evaluated annually using neuropsychological tests to detect subtle changes in memory and other cognitive function designed to detect transition to MCI and dementia.  Many existing and planned research projects at UK are dependent on autopsy specimens from normal subjects and those with MCI or early AD.  The core holds important consensus diagnostic conferences and relates closely to the Neuropathology and Biostatistics and Data Management Cores.  The Clinical Core will provide expert dementia diagnostic services in a referral Memory Disorders Evaluation Clinic for approximately 300 patients per year a group which serves as a recruiting pool for the Research Clinic and for clinical trials and other research studies.  The core will expand and maintain a clinic for African Americans in Lexington the Kentucky Clinic North Minority Emphasis Clinic providing longitudinal care and broadening research opportunities to an understudied population.  This core participates in the NIA LOAD genetic initiative NACC funded studies and ADCS trials.  All appropriate data are collected and submitted to NACC in a timely manner.

project_terms:
African American;Alzheimer's Disease;Autopsy;Biometry;Caring;Clinic;Clinical;Clinical Trials Other;Computer Retrieval of Information on Scientific Projects Database;Consensus;Data;Dementia;Diagnosis clinical;Diagnostic;Diagnostic Services;Disease;Evaluation;Funding;Genetic Load;Goals;Grant;Institution;Kentucky;Memory;Memory Disorders;Minority;Mission;Neuropsychological Tests;Participant;Patient Care;Patients;Population;Recruitment Activity;Research;Research Personnel;Research Project Grants;Resources;Rural;Source;Specimen;Support of Research;United States National Institutes of Health;Universities;aged;base;cognitive function;data management;design;mild cognitive impairment;neuropathology;normal aging;research study;symposium


application_id: 7607318
project_number: 3M01RR002602-22S1
project_title: EARLY TREATMENT OF ALS WITH NUTRITION AND NIPPV
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5328
contact_pi_person_id: 1975664
contact_pi: KASARSKIS, EDWARD JOSEPH
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.This is a multicenter Pilot Study to develop methods for a definitive Phase III trial. The specific aims of this Pilot Study are 1) To develop and validate strategies to improve tolerability of NIPPV to identify factors that influence acceptance of this treatment modality and to evaluate measures of early respiratory dysfunction; and 2) To develop and validate methods to determine energy balance in ALS.

project_terms:
Amyotrophic Lateral Sclerosis;Clinical Trials Phase III;Computer Retrieval of Information on Scientific Projects Database;Early treatment;Functional disorder;Funding;Grant;Institution;Measures;Methods;Modality;Pilot Projects;Research;Research Personnel;Resources;Science of nutrition;Source;United States National Institutes of Health;energy balance;improved;respiratory


application_id: 7607317
project_number: 3M01RR002602-22S1
project_title: SECONDARY PREVENTION OF SMALL SUBCORTICAL STROKES (SPS3)
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5327
contact_pi_person_id: 8543099
contact_pi: VAISHNAV, ANAND
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The overall aim of the Secondary Prevention of Small Subcortical Strokes (SPS3) project is to define efficacious therapies for cerebral small artery disease and its two most common clinical manifestations: small subcortical strokes (S3 also called lacunar strokes) and cognitive decline (vascular dementia). Optimal antiplatelet therapy and antihypertensive management of S3 patients to reduce stroke recurrence and cognitive decline has not been defined and is likely to yield important health benefits. Primary aims are to determine whether combination antiplatelet therapy consisting of aspirin plus clopidogrel is superior to aspirin for reducing recurrent stroke cognitive decline and major vascular events. Also to determine whether "intensive" blood pressure lowering to a specific target range is superior to "usual" hypertension management for reducing recurrent stroke cognitive decline and major vascular events.

project_terms:
Antihypertensive Agents;Arteries;Aspirin;Blood Vessels;Cerebrum;Clinical;Computer Retrieval of Information on Scientific Projects Database;Dementia Vascular;Disease;Event;Funding;Grant;Health Benefit;Hypertension;Hypotension;Impaired cognition;Institution;Patients;Range;Recurrence;Research;Research Personnel;Resources;Secondary Prevention;Source;United States National Institutes of Health;clopidogrel;stroke


application_id: 7607316
project_number: 3M01RR002602-22S1
project_title: BORTEZOMIB WITH WEEKLY IDARUBICIN FOR THE TREATMENT OF AML
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5326
contact_pi_person_id: 8535501
contact_pi: HOWARD, DIANNA S
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.To determine safety and efficacy  of bortezomib (PS-341) in combination with idarubicin in a phase I and II clinical trial for patients with AML. The rationale for this novel clinical trial is based on our preclinical studies demonstrating a strong tumor-specific induction of apoptosis for primary human AML cells using the combination of bortezomib and idarubicin. Elderly and relapsed AML patients have been targeted for this study due to the lack of a "standard of care" and poor outcomes for these patients owing to a preponderance of poor-risk cytogenetics multi-drug resistance and antecedent co-morbidities. We expect to define dose-limiting toxicities and a maximal tolerated dose of bortezimib when combined with idarubicin in a phase I study; subsequently safety and efficacy of the combination at the designated dose will be explored in a phase II study with expanded enrollment. We anticipate that with this regimen we will observe potent anti-leukemia activity complete clinical remissions and less overall toxicity.

project_terms:
Bortezomib;Caring;Cells;Clinical;Clinical Trials;Clinical Trials Phase I;Clinical Trials Phase II;Computer Retrieval of Information on Scientific Projects Database;Cytogenetics;Disease remission;Dose;Dose-Limiting;Elderly;Enrollment;Funding;Grant;Human;Idarubicin;Induction of Apoptosis;Institution;Maximum Tolerated Dose;Morbidity - disease rate;Multi-Drug Resistance;Outcome;PS341 cpd;Patients;Phase;Protocols Treatment;Relapse;Research;Research Personnel;Resources;Risk;Safety;Source;Standards of Weights and Measures;Toxic effect;United States National Institutes of Health;base;leukemia;novel;preclinical study;tumor


application_id: 7607315
project_number: 3M01RR002602-22S1
project_title: CLOPIDOGREL WITH ASPIRIN AFTER OFF-PUMP CORONARY ARTERY BYPASS SURGERY
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5325
contact_pi_person_id: 6795654
contact_pi: AKERS, W S
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The purpose of this study is to determine the safety of clopidogrel in combination with aspirin during the immediate postoperative period following OPCAB surgery. We hypothesize that there will be no difference in chest tube drainage in patients who have undergone OPCAB surgery and randomized to aspirin or aspirin plus clopidogrel during the immediate postoperative period.

project_terms:
Aspirin;Chest Tubes;Computer Retrieval of Information on Scientific Projects Database;Coronary Artery Bypass;Drainage procedure;Funding;Grant;Institution;Operative Surgical Procedures;Patients;Postoperative Period;Pump;Purpose;Randomized;Research;Research Personnel;Resources;Safety;Source;United States National Institutes of Health;clopidogrel


application_id: 7607314
project_number: 3M01RR002602-22S1
project_title: ALZHEIMER'S DISEASE GENETICS INITIATIVE: THE MULTIPLEX FAMILY STUDY
administering_ic: NCRR
award_notice_date: 2007-04-10
application_type: 3
activity_code: M01
ic: RR
serial_number: 002602
suffix: S1
project_start_date: 2006-04-01
project_end_date: 2008-03-31
study_section: Clinical Research Review Committee[RIRG-G]
subproject_number: 5324
contact_pi_person_id: 1958116
contact_pi: SMITH, CHARLES K
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH sourceand thus could be represented in other CRISP entries. The institution listed isfor the Center which is not necessarily the institution for the investigator.The purpose of the NIA Genetics Initiative: Multiplex Family Study is to identify families with multiple members diagnosed with late-onset Alzheimer's Disease. Families will be characterized clinically and blood samples will be collected to establish cell lines. If a blood sample is not available autopsy samples will be collected for DNA extraction and storage. Our goal is to recruit 1000 families in three years.  Clinical and demographic data from these families will be collected at the local site and coded data without identifiers will be sent and included in a national database of families with Alzheimer's Disease. This database along with biological samples will be housed at the National Cell Repository for Alzheimer's Disease (NCRAD) at Indiana University. The biological samples and data from these families will be available to qualified researchers who must sign a Material Transfer Agreement before receiving DNA and data. An oversight committee knows as the Cell Bank Advisory Committee (CBAC) will review and monitor the process of family identification and enrollment data collection the establishment of cell lines and access to samples.

project_terms:
Advisory Committees;Alzheimer's Disease;Autopsy;Biological;Blood specimen;Cell Line;Cells;Clinical;Code;Computer Retrieval of Information on Scientific Projects Database;DNA;Data;Data Collection;Databases;Diagnosis;Enrollment;Family;Family Process;Family Study;Funding;Genetic;Goals;Grant;Housing;Indiana;Institution;Late Onset Alzheimer Disease;Monitor;Purpose;Qualifying;Recruitment Activity;Research;Research Personnel;Resources;Sampling;Site;Source;Transfer Agreement;United States National Institutes of Health;Universities;cell bank;established cell line;member;repository


application_id: 7607312
project_number: 7R01DA020757-03
project_title: Smoking Cessation Practices in Community Tx Programs
administering_ic: NIDA
award_notice_date: 2008-06-03
application_type: 7
activity_code: R01
ic: DA
serial_number: 020757
program_official: HILTON, THOMAS F
project_start_date: 2006-04-01
project_end_date: 2011-03-31
study_section: ZDA1-RXL-E(28)
contact_pi_person_id: 8146786
contact_pi: KNUDSEN, HANNAH
other_pis: Not Applicable
congressional_district: 06
department: PSYCHOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2008-04-01
project_abstract:
The delivery of health services to promote smoking cessation may substantially reduce cancer-relatedmorbidity and mortality. However there has been little research conducted within healthcare settings tomeasure the delivery of these services particularlywithin those organizations that serve client pop-ulations with high rates of tobacco use. There is little national-level data on the delivery of smokingcessation (and other tobacco use) services in substance abuse treatment settings. Furthermore there is nodata regarding the adoption and implementation of the Public Health Service clinical practice guidelineTreating Tobacco Use and Dependence in these facilities. Additional gains in cancer prevention may beachieved if smoking cessation services are also available to the counseling staff within these healthcareorganizations. Environmental policies may also prevent cancer for clients as well as center staff. The pro-posed research would gather organizational-level and counselor-level data by building upon three exist-ing nationally representative samples of facilities: 362 publicly funded specialty substance abuse treatmentcenters 401 privately funded centers and 400 therapeutic communities. Telephone interviews with pro-gram directors will determine whether centers have: 1) adopted and implemented the guideline includingthe 5 A's pharmacotherapies and psycho-social interventions; 2) adopted environmental tobacco-relatedpolicies; and 3) provide insurance coverage for employee smoking cessation. Mail questionnaires will bedistributed to counselors to assess their attitudes toward smoking cessation and the extent to which theydeliver these services. Integration of these data with information collected from these facilities in 2002-2003 will allow for multivariate modeling of the organizational characteristics associated with guidelineadoption and implementation as well as a longitudinal analysis of pharmacotherapy adoption. Theinformation collected in this research would represent valuable information about the services delivered toa population at high-risk of tobacco-related cancers and identify barriers to such service delivery.

project_terms:
Abstinence;Address;Adopted;Adoption;Adult;American;Area;Attitude;Behavior;Behavior Therapy;Bupropion;Bupropion HCl;Characteristics;Client;Clinical Practice Guideline;Collection;Communities;Counseling;Data;Dependence;Dependence Nicotine;Effectiveness;Employee;Environmental Tobacco Smoke;Evidence based intervention;Funding;Georgia USA;Georgia Western Asia;Goals;Gold;Guidelines;Hand functions;Health Expenditures;Health Personnel;Health Services;Health Services Accessibility;Healthcare;Healthcare Systems;Individual;Insurance Coverage;Intervention;Life;Link;Literature;Mails;Malignant Neoplasms;Measures;Medical Specialities;Modeling;Models Organizational;Morbidity - disease rate;Mortality Vital Statistics;Motivation;Nature;Nicotine;Numbers;Perception;Persons;Pharmacotherapy;Policies;Policy Environmental;Population;Prevention strategy;Principal Investigator;Professional counselor;Questionnaires;Rate;Research;Research Personnel;Resources;Risk;Sampling;Services;Site;Smoke;Smoking;Substance Abuse Treatment Centers;Substance abuse problem;System;Techniques;Telephone Interviews;Therapeutic community technique;Time;Tobacco;Tobacco use;United States Public Health Service;Universities;Variant;Withholding Treatment;Work;Workplace;base;cancer prevention;cancer type;cigarette smoking;cost;data integration;early /brief intervention /therapy;evidence based guidelines;follow-up;innovation;interest;member;nicotine replacement;organizational structure;prevent;programs;public health medicine (field);smoking cessation;social;treatment center;treatment organization;treatment program;willingness


application_id: 7600704
project_number: 1R41DE018589-01A2
project_title: Natural Product Protease Inhibitors: Therapeutics for Virulence of Oral Pathogens
administering_ic: NIDCR
award_notice_date: 2009-09-15
opportunity_number: PA-08-051
application_type: 1
activity_code: R41
ic: DE
serial_number: 018589
suffix: A2
program_official: LUNSFORD, DWAYNE
project_start_date: 2009-09-15
project_end_date: 2011-11-30
study_section: Special Emphasis Panel[ZRG1 MOSS-K (11)]
contact_pi_person_id: 8367053
contact_pi: HUANG, CHIFU BRAD
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 140647046
duns_number: 140647046
fips: US
organization_id: 10002330
organization_name: ORACEUTICALS, INC.
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic For-Profits
organization_zip: 405032916
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-09-15
project_abstract:
DESCRIPTION (provided by applicant):  Oral infections associated with the gingival margin and subgingival sulcus lead to host inflammatory responses. Gingivitis is primarily a response to the bacteria in plaque. This "disease" affects nearly everyone in the population at some time during their life. Periodontitis is a multifactorial disease that encompasses the hard and soft tissue microbial colonization (with/without invasion) inflammatory responses and adaptive immune responses. Periodontal inflammation and tissue destruction result from variations in the subgingival bacterial ecology that trigger deleterious host responses with current evidence suggesting altered production and/or release of an array of destructive host mediators that lead to tissue destruction. However recent studies have supported that certain putative oral pathogens produce a array of physiologic gene products (e.g. proteases) that have the capacity to engage and stimulate various host cell receptors resulting in a substantially enhanced synthesis of biomolecules that have been implicated in tissue destruction (e.g. IL-1ss TNF1). Thus while strategies of combating gingivitis are primarily designed to be managed by mechanical and/or nonspecific antimicrobial therapies to decrease the overall magnitude of bacterial challenge in the plaque; targeting periodontitis requires additional considerations relative to unique features of the microbial composition of the biofilms and potentially critical host cell signaling mechanisms that may be unique to these pathogens. This STTR proposal is focusing on a strategy to identify natural plant-based agents that will inhibit proteases from significant oral pathogens P. gingivalis T. denticola and T. forsythia. These proteases have been shown to relate to disease sites in vitro growth and survival production of inflammatory mediators and in vivo virulence. Thus interfering with the activity of these crucial molecules should provide an innovative new strategy to biologically interfere with infection and disease processes provoked by these oral pathogens. Gingivitis and periodontitis affect as large a proportion of the global population as any disease(s) known to mankind. Thus identifying and developing more effective therapeutic regimens targeting aspects of the chronic infection and inflammation would provide a significant benefit to these individuals. Specific Aims are to document the effect of select natural products on the growth host cell triggering and virulence capacity of these bacteria.   
  
PUBLIC HEALTH RELEVANCE: This STTR proposal aims to evaluate natural products for their ability to improve oral health by developing therapeutic treatments for gingival inflammation and tissue distruction. Specific Aims are to isolate and analyze natural products with anti-proteases properties to treat oral infections/diseases.

project_terms:
Abscess;Acute;Affect;Anaerobic Bacteria;Anti-Infective Agents;Arginine;Bacteria;Bacterial Adhesins;Biological;Biological Factors;Biological Process;Carya;Cells;Characteristics;Chemicals;Chronic;Clinical Trials;Complex;Connective Tissue;Cysteine Protease;Defense Mechanisms;Degradation Pathway;Detection;Disease;Disorder by Site;Dose;Ecology;Effectiveness;Environment;Enzyme Inhibitor Drugs;Enzyme Inhibitors;Enzymes;Epithelial;Epithelial Cells;Etiology;Exhibits;Forsythia;Frequencies (time pattern);Gingiva;Gingivitis;Goals;Grant;Growth;Halitosis;Host Defense Mechanism;Human;Immune response;In Situ;In Vitro;Individual;Infection;Inflammation;Inflammation Mediators;Inflammatory;Inflammatory Response;Lead;Lesion;Libraries;Life;Link;Literature;Lys-gingipain;Mechanics;Mediating;Mediator of activation protein;Metabolic;Metabolism;Microbe;Microbial Biofilms;Modeling;Mus;Mutation;Nutrient;Oral;Oral cavity;Oral health;Outcome;Pathogenicity;Pathway interactions;Pattern;Pecans;Peptide Hydrolases;Periodontal Diseases;Periodontal Infection;Periodontal Ligament;Periodontitis;Periodontium;Pharmaceutical Resources;Phase;Physiological;Physiology;Phytochemical;Plant Extracts;Plants;Population;Porphyromonas gingivalis;Principal Investigator;Process;Production;Property;Protease Inhibitor;Proteinase-Activated Receptors;Proteins;Receptor Cell;Relative (related person);Reporting;Research;Role;Screening procedure;Signal Transduction;Site;Small Business Technology Transfer Research;Structure;Taxon;Testing;Therapeutic;Therapeutic Intervention;Time;Tissues;Tooth structure;Treatment Protocols;Treponema denticola;Variant;Virulence;Virulent;alveolar bone;antimicrobial;bactericide;base;chemokine;chymotrypsin;combat;commensal microbes;cytokine;design;enzyme activity;extracellular;gingipain;human disease;improved;in vivo;inhibitor/antagonist;innovation;microbial;microbial colonization;microorganism;mouse model;novel;oral biofilm;oral infection;oral pathogen;pathogen;periodontopathogen;prevent;programs;proteinase T;public health relevance;rapid growth;receptor;research study;response;soft tissue;tooth surface

public_health_relevance:
Principal Investigator/Program Director (Last First Middle): Huang Chifu BradPROJECT NARRATIVEThis STTR proposal aims to evaluate natural products for their ability to improve oral health bydeveloping therapeutic treatments for gingival inflammation and tissue distruction. Specific Aims areto isolate and analyze natural products with anti-proteases properties to treat oral infections/diseases.PHS 398/2590 (Rev. 09/04) Page 18 Continuation Format Page


application_id: 7600635
project_number: 5R01HD023333-17
project_title: Listening Skills in children with and without cochlear implants
administering_ic: NICHD
award_notice_date: 2009-04-01
application_type: 5
activity_code: R01
ic: HD
serial_number: 023333
program_official: KAU, ALICE S
project_start_date: 1989-04-01
project_end_date: 2012-03-31
study_section: Auditory System Study Section[AUD]
contact_pi_person_id: 1963999
contact_pi: WIGHTMAN, FREDERIC L
other_pis: Not Applicable
congressional_district: 03
department: PSYCHOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF ARTS AND SCIENCES
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-04-01
project_abstract:
DESCRIPTION (provided by applicant): The long term goal of this program is a complete understanding of the capabilities and limitations of auditory information processing in children the development of auditory processing skills and how that developmental course may be affected by hearing impairment deafness and the use of a cochlear mplant. The current focus of the project is on the strategies used by children to segregate desired auditory signals from interfering sounds. Results to date suggest that most young children display a remarkable nability to perform this segregation in simple detection tasks and in tasks requiring attention to a target speech message in the presence of other speech distracters. The data also reveal large individual differences in source segregation ability with some teenagers demonstrating child-like performance and some young school-aged children demonstrating adult-like performance. The adult-child differences are argely consistent with what iresults. The new work also addresses the special selective attention problems faced by children and adults with cochlear implants and evaluates strategies by which selective attention can be enhanced. Auditory selective attention is quantified in four kinds of tasks: 1) simple signal detection in which the target signal is masked by random multicomponent tonal complexes; 2) a speech fundamental frequency discrimination task; 3) speech recognition tasks both with and without a visual representation of the speaker; 4) spatial segregation tasks in which the target message and the distracter are spatially separated. The aim of the first task is to quantify auditory selective attention within the constraints of a simple one-parameter model. The second task will produce a scale of talker similarity which will then be used to predict the impact of talker similarity in the selective attention tasks. The third and fourth tasks explore means by which selective attention can be enhanced eithssessed. The overall importance of this project lies in its study of communication situations common in everyday life. Speech communication in noisy environments is an especially important issue for children who are developing speech and language and the results of this project will add important new knowledge about how children and adults are able to address this issue.

project_terms:
3 year old;Acoustics;Address;Adolescence;Adopted;Adult;Affect;Age;Algorithms;Attention;Auditory;Child;Child Development;Cochlear Implants;Communication;Complex;Cues;Data;Deafness;Dependence;Detection;Development;Discrimination (Psychology);Ear structure;Environment;External auditory canal structure;Failure (biologic function);Frequencies (time pattern);Funding;Goals;Hearing;Hearing Impaired Persons;Implant;Individual;Individual Differences;Knowledge;Laboratories;Language;Life;Lipreading;Masks;Measurable;Measurement;Measures;Modeling;Noise;Participant;Performance;Peripheral;Population;Positioning Attribute;Process;Publishing;Reading;Rehabilitation therapy;Relative (related person);Research;Resolution;School-Age Population;Signal Transduction;Simulate;Source;Speech;Stimulus;Techniques;Teenagers;Testing;Training;Uncertainty;Visual;Weight;Work;age effect;age related;base;expectation;hearing impairment;information processing;programs;research study;segregation;selective attention;simulation;skills;sound;speech recognition;stimulus processing;virtual


application_id: 7600531
project_number: 5R01DA022967-02
project_title: African American Female Drug Users: HIV Health Disparities & Criminality
administering_ic: NIDA
award_notice_date: 2008-12-19
opportunity_number: PA-07-114
application_type: 5
activity_code: R01
ic: DA
serial_number: 022967
program_official: JONES, DIONNE
project_start_date: 2008-04-01
project_end_date: 2013-01-31
study_section: Behavioral and Social Consequences of HIV/AIDS Study Section[BSCH]
contact_pi_person_id: 6264981
contact_pi: OSER, CARRIE BETH
other_pis: Not Applicable
congressional_district: 06
department: SOCIAL SCIENCES
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF ARTS AND SCIENCES
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
DESCRIPTION (provided by applicant): The overall goal of this study is to understand how drug use and criminality are related to health disparities particularly HIV and service utilization among African American drug using and non-drug using women across criminal justice status. While drug use is similar across racial groups in the US African Americans are disproportionately more likely to experience severe health consequences and criminal involvement as a result of drug misuse. Adequate health care may not be received by African American female offenders because they experience the burden of their race class gender and criminal offender status. There is limited scientific data to help understand the linkages between health disparities such as HIV untreated drug abuse barriers to service utilization and status as a criminal offender among African American females. This study is significant because of its potential to identify differences in health disparities and service utilization among African American drug using and non-drug using women in selected levels of criminal justice status (intensive correctional supervision-prison (n=200) moderate correctional supervision-jail (n=200) community supervision-probation (n=200) and no criminal justice involvement (n=200)). All 800 African American females will be followed longitudinally for three 6-month intervals to examine health status and the use of health services across time. The specific aims are: (1) To describe the prevalence of health problems among African American women across criminal justice status and drug use status; (2) To determine the cultural predisposing historical health and potential enabling factors that are predictors of health problems among African American drug using and non-drug using women across criminal justice status over 18 months; (3) To describe the prevalence of untreated health problems the patterns of health services utilization and the cultural barriers to service utilization among African American women across criminal justice status and drug use status; and (4) To examine the factors that predict the likelihood of using health services among African American drug using and non-drug using women across criminal justice status over 18 months. The significance of this study includes the potential to provide criminal justice systems-level data for health planning and health policy for prevention intervention and treatment of African American female drug users.   
  
This study is significant to the public health field because of its potential to understand the severity of health disparities among African American women across criminal justice status and drug use status and to predict health status and the use of health services over time. This knowledge of African American females can be used as a foundation for future criminal justice systems-level interventions to increase the use of preventative health care and subsequently reduce the need for expensive medical services as well as to decrease HIV risk behaviors including drug use unprotected sex and recidivism.

project_terms:
Accident and Emergency department;African American;Alcohol or Other Drugs use;Alcohols;Applications Grants;Biological Assay;Chlamydia;Communities;Criminal Justice;Data;Dependence;Development;Drug abuse;Drug abuser;Drug usage;Drug user;Economics;Enabling Factors;Epidemiology;Event;Female;Foundations;Fright;Future;Gender;General Population;Goals;Gonorrhea;HIV;Health;Health Personnel;Health Planning;Health Policy;Health Services;Health Status;Healthcare;Hepatitis C;Hepatitis C virus;Hospitalization;Imprisonment;Incidence;Individual;Inpatients;Intervention;Interview;Jail;Kentucky;Knowledge;Life;Literature;Location;Mediating;Medical;Mental Health;Modeling;Multivariate Analysis;NIH Program Announcements;Participant;Patient Self-Report;Pattern;Pharmaceutical Preparations;Physicians;Population;Prevalence;Preventive Intervention;Prisoner;Prisons;Race;Recruitment Activity;Reporting;Research;Risk Behaviors;Sampling;Series;Seroprevalences;Services;Severities;Sexually Transmitted Diseases;Structure;Substance abuse problem;Supervision;Surveys;System;Time;Trust;Universities;Unsafe Sex;Woman;Women's Health;Work;alcohol research;base;criminal offending;experience;follow-up;health care service utilization;health disparity;innovation;longitudinal design;non-drug;offender;physical conditioning;probation;public health medicine (field);racism;recidivism;service utilization;time use


application_id: 7600465
project_number: 5R01CA113932-05
project_title: Structure M.tuberculosis Adenosine Kinase Design Antimicrobial Nucleoside Analogs
administering_ic: NCI
award_notice_date: 2009-03-12
application_type: 5
activity_code: R01
ic: CA
serial_number: 113932
program_official: BRESLAU, ERICA S
project_start_date: 2005-05-01
project_end_date: 2012-03-31
study_section: Community-Level Health Promotion Study Section[CLHP]
contact_pi_person_id: 1871398
contact_pi: DIGNAN, MARK B
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-04-01
project_abstract:
DESCRIPTION (provided by applicant): The University of Kentucky's Cancer Control Program Department of Behavioral Science  Kentucky Cancer Program and community partners are proposing a five-year community-based participatory project to increase colorectal cancer screening in rural Appalachian Kentucky (51 counties in eastern Kentucky). Compared with the rest of the U.S. Appalachian Kentucky is medically underserved economically distressed and disproportionately burdened with different types of cancer. Data from the Behavioral Risk Factor Surveillance System indicates that approximately 36% of respondents in Appalachian Kentucky reported screening for colorectal cancer (FOBT or flexible sigmoidoscopy or colonoscopy) in accordance with guidelines of the US Preventive Services Task Force compared to 43.5% in Kentucky and 53% nationwide.  Specific aims of this project are to: 1) Build on a foundation of community partnerships in Appalachian Kentucky and develop a network of community partners capable of fostering colorectal cancer screening; 2) Use results from a pilot project and in collaboration with community partners pretest an intervention to increase screening for colorectal cancer in rural Appalachian Kentucky; 3) Recruit primary health care providers for the project conduct a baseline assessment and implement an intervention to increase colorectal cancer screening in primary care practices; and 4) Evaluate the effectiveness of the intervention in increasing colorectal cancer using a randomized design involving primary care practices assigned to intervention or control based on a readiness to change score and conduct qualitative key informant interviews and process evaluations. Methods for achieving these aims are described in detail in Section D (Research Design and Methods) and include conducting focus groups recruiting 64 primary care practices (32 control 32 intervention) delivering an educational intervention consisting of 4 modules collecting colorectal cancer screening data from 60 medical records/intervention practice and assessing the impact of the intervention.

project_terms:
Adenosine Kinase;Advisory Committees;Behavioral Risk Factor Surveillance System;Behavioral Sciences;Cancer Control;Collaborations;Colonoscopy;Colorectal Cancer;Communities;Community Networks;County;Data;Distress;Educational Intervention;Effectiveness of Interventions;Evaluation;Flexible fiberoptic sigmoidoscopy;Focus Groups;Fostering;Foundations;Guidelines;Health Personnel;Intervention;Interview;Kentucky;Malignant Neoplasms;Medical Records;Methods;Mycobacterium tuberculosis;Pilot Projects;Preventive;Primary Health Care;Process;Randomized;Readiness;Recruitment Activity;Reporting;Research Design;Respondent;Rest;Rural;Services;Structure;Universities;antimicrobial;base;cancer type;colorectal cancer screening;design;informant;medically underserved;nucleoside analog;programs


application_id: 7600369
project_number: 5R01AG026307-04
project_title: Repetitive Thought Stress and Immunity in Older Adults
administering_ic: NIA
award_notice_date: 2009-04-15
opportunity_number: PA-05-027
application_type: 5
activity_code: R01
ic: AG
serial_number: 026307
program_official: NIELSEN, LISBETH
project_start_date: 2006-07-15
project_end_date: 2011-04-30
study_section: Biobehavioral Mechanisms of Emotion, Stress and Health Study Section[MESH]
contact_pi_person_id: 1886687
contact_pi: SEGERSTROM, SUZANNE C.
other_pis: Not Applicable
congressional_district: 06
department: PSYCHOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF ARTS AND SCIENCES
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
DESCRIPTION (provided by applicant): The effects of stressors on the immune system are particularly relevant for older adults: Potent stressors such as bereavement become more common with age immune reactions to stress grow larger with age and vulnerability to immunological dysregulation and immunologically mediated disease increases with age. Previous studies have linked stressors in old age with increased distress and physiological dysregulation including depression high levels of cortisol poor responses to vaccination and high levels of the proinflammatory cytokine IL-6. The proposed research will address limitations of the extant literature by focusing on the prospective effects of stressors among older adults and by including individual differences in repetitive thought (RT) that is the cognitive interpretation and processing of stressful events. Individual differences in RT can create vulnerability or resilience to stressors: Negative uncontrolled and intrusive thought (e.g. worry) can prolong and amplify negative consequences whereas positive and controlled thought (e.g. reflection) can buffer against negative consequences and promote positive consequences such as growth. In this 5-year longitudinal prospective study married adults aged 60 or older (N = 183) will be interviewed and will collect saliva samples for cortisol every 6 months; they will be vaccinated annually against influenza and serum for antibody and IL-6 will be collected before and after vaccination and at the end of influenza season. The primary aim of the study is to test the following predictions: (1) stressors and RT predict psychological and physiological indices of health or dysregulation; (2) RT moderates the effects of stressors; (3) psychological indices (e.g. depression) mediate the relationship between stressors and RT and physiology. A secondary aim of the study is to relate cortisol autonomic activity and inhibition IL-6 and antibody to each other and to evidence of influenza infection. Another secondary aim is to validate the dimensional structure of RT in older adults and link trait RT (e.g. trait worry) to episodic RT (e.g. thoughts about a specific stressor). Relevance to public health: Stress in older adults can increase their vulnerability to both mental and physical illness. This research will test whether thought styles such as worry put older adults at greater risk. This knowledge could be used to identify and intervene with the most at-risk individuals.

project_terms:
Address;Adult;Affect;Age;Antibodies;Antibody Formation;Bereavement;Buffers;Cognitive;Disease;Distress;Elderly;Environment;Event;Growth;Health;Hydrocortisone;Immune;Immune system;Immunity;Individual;Individual Differences;Influenza;Influenza virus vaccine;Interleukin-6;Interview;Knowledge;Link;Literature;Measures;Mediating;Neurosecretory Systems;Perception;Personal Satisfaction;Pharmaceutical Preparations;Physiological;Physiology;Process;Prospective Studies;Psyche structure;Psychosocial Stress;Reaction;Regulation;Research;Research Personnel;Risk;Saliva;Sampling;Seasons;Series;Serum;Stress;Stressful Event;Structure;Sympathetic Nervous System;Testing;Thinking function;Vaccinated;Vaccination;Vaccines;Well in self;aged;cytokine;depression;improved;indexing;programs;prospective;psychologic;public health medicine (field);resilience;response;stressor;thought control;trait;young adult


application_id: 7600363
project_number: 5P30ES014443-03
project_title: Center for Environmental Genomics and Integrative Biology
administering_ic: NIEHS
award_notice_date: 2009-04-03
opportunity_number: RFA-ES-05-008
application_type: 5
activity_code: P30
ic: ES
serial_number: 014443
program_official: QUINN, ASHLINN KO
project_start_date: 2007-06-04
project_end_date: 2011-03-31
study_section: Environmental Health Sciences Review Committee[EHS]
contact_pi_person_id: 6221833
contact_pi: RAMOS, KENNETH S.
other_pis: Not Applicable
congressional_district: 03
department: BIOCHEMISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
DESCRIPTION (provided by applicant): The main goal of the Center for Environmental Genomics and Integrative Biology (CEGIB) is to support outstanding basic and translational investigations into the etiology of environmental disease and the development of new approaches to manage these conditions.   Center investigators with diverse disciplinary backgrounds and research interests will combine their efforts to: 1) study genetic molecular and cellular mechanisms of environmental injury 2) evaluate the ethical legal and social implications of genomics research and 3) advance the emerging fields of environmental genomics and intergrative biology.   CEGIB will provide scientific leadership and administrative support for creation of a synergistic inter- and trans-disciplinary network structure that brings together University of Louisville investigators to focus on the study of environmental disease.   The Center will support facility cores in Bioinformatics Biostatistics and Computational Biology and Integrative Health Sciences.  These cores will provide expertise and facilities to advance research efforts in the areas of environmental cardiology environmental carcinogenesis and developmental origins of health and disease.  The Center structure also includes programs in Career Development for Junior Investigators and a Pilot Project Program to encourage development of novel research approaches and data collection that enable pursuit of other funding mechanisms.   A Community Outreach and Education Core has been included to facilitate translation of scientific information into knowledge that can use be used to reduce health disparities of underserved Hispanic populations in the greater Louisville area.   CEGIB is in a unique position to meet its objectives given the depth of expertise and talent in environmental health molecular biology bioinformatics and computational biology and ELSI research and strong institutional emphasis on bench-to-bedside and bench-to-community investigations.   The focus on environmental  genomics and integrative biology reflects the interests of its members in advancing molecular investigations and ELSI research of environmentally related diseases.   The creation of a Center with a resolute focus on environmental genomics and integrative biology will further NIEHS' goal to understand the etiology of environmental disease at its most fundamental levels and provide a visible infrastructure for advancement of the Institute's agenda in the post-genomic era.


application_id: 7600362
project_number: 5P30ES014443-02
project_title: Community Outreach & Education Core
administering_ic: NIEHS
application_type: 5
activity_code: P30
ic: ES
serial_number: 014443
study_section: Environmental Health Sciences Review Committee[EHS]
subproject_number: 9003
contact_pi_person_id: 9898612
contact_pi: RAMOS, IRMA N
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2008-04-01
budget_end_date: 2009-03-31
funding_mechanism: Research Centers
project_abstract:
Goals and Theme of the Community Outreach Educational Core (COEC)The primary goal of the COEC will be to educate residents in the Louisville Metropolitan Area (nine counties inKentucky and four counties in Indiana) on the importance of interactions between genes environment cultureand disease. Our focus during the first four years will be the fast-growing Hispanic community of Shelbyville inShelby County Kentucky. This community consists of 4-8 thousand individuals many of which lack basicsocial and economic infrastructure support and consequently a group deficient in essential tools for promotionof a healthy community. As the Center matures and research programs are established in both the Hispanicand African American communities of Louisville the COEC will extend its educational programs to WestLouisville another disadvantaged community in close proximity to a large industrial chemical complex knownas Rubbertown. These efforts will be complementary to those of the Integrated Health Sciences Facility Core(IHSFC). As detailed in Section 7A the IHSFC will initially work with the more established and environmentallyfocused community-based organizations in West Louisville with plans to increasingly involve Hispanic-focusedorganizations as they acquire a higher level of knowledge about environmental health through the work of theCOEC. This approach will create a synergistic relationship that can significantly advance the Center's goalsand its impact.To achieve our primary goal we seek to empower the community of Shelbyville with sound medical andscientific information on the role of genes in health and disease and how environmental factors and lifestylepractices influence health outcomes. We will begin by working with existing community organizations toidentify community leaders who will be trained by COEC staff and in turn these leaders will train others in theircommunity using a well-established train-the-trainer model (Ramos I. 2003). This approach has been shownto gradually build an environmental health infrastructure that can positively impact the community and itsresidents.The ultimate goal of the COEC is to build a self-sustainable educational program that persists within the targetcommunity after the intervention is completed. Modern theorists have proposed that systems thinking can beused to tackle intractable social issues such as environmental health in depressed communities. Unlikeprevious social theories influenced by a reductionist approach to social problems (reminiscent of theapproaches used in the biomedical sciences) theories developed through systems thinking incorporate theawareness that the entry of new knowledge may lead to conflict between those who are or perceivethemselves to be at risk and those perceived as being responsible for creating or preventing that risk. Thesesocial tensions must be factored into our community outreach efforts with the expectation that application ofintegrative approaches will enhance the quality of its products of the COEC.

project_terms:
African American;Area;Awareness;Chemicals;Communities;Complex;Conflict (Psychology);Core Facility;County;Depressed mood;Disadvantaged;Disease;Economics;Education and Outreach;Educational Curriculum;Educational aspects;Effectiveness;Environment;Environmental Health;Environmental Risk Factor;Evaluation;Genes;Goals;Health;Health Sciences;Health Status;Hispanics;Human Resources;Indiana;Individual;Institution;Intervention;Kentucky;Knowledge;Lead;Life Style;Medical;Modeling;Outcome;Outreach Community;Plant Roots;Research;Research Infrastructure;Resources;Risk;Role;Science;Services;Social Problems;Sound - physical agent;System;Thinking function;Trainers Training;Training;Work;base;community organizations;design;expectation;instrument;metropolitan;prevent;programs;social;theories;tool


application_id: 7600361
project_number: 5P30ES014443-02
project_title: Facility Core B: Bioinformatics Biostatistics & Computational Biology
administering_ic: NIEHS
application_type: 5
activity_code: P30
ic: ES
serial_number: 014443
study_section: Environmental Health Sciences Review Committee[EHS]
subproject_number: 9002
contact_pi_person_id: 8436899
contact_pi: PARRISH, RUDOLPH SANDERS
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2008-04-01
budget_end_date: 2009-03-31
funding_mechanism: Research Centers
project_abstract:
BIOINFORMATICS BIOSTATISTICS AND COMPUTATIONAL BIOLOGY FACILITY COREA. SPECIFIC AIMSThe availability of genomic sequences from a growing number of human and model organisms has fueled anexplosion of data information and knowledge that has a clear and present impact on our ability to decipherkey genetic signals and responses in the exposure-disease continuum. This information revolution is reflectedin the public Molecular Biology Database Collection (http://nar.oupiournals.org/). which now numbers 858 [1].Consider Gene Expression Omnibus which is the principal NIH repository for high-content gene expressiondata (http://www.ncbi.nlm.nih.gov/geo/) [2]. GEO is growing by 100 samples daily to increase from 18235 inJune 2004 to 69017 samples in January 2006 (Knudsen personal observation).As the genomics repositories approach 'peda-bytes' of digital information environmental health scienceresearchers are faced with the challenge of mobilizing vast data into cogent models regarding the biology ofinformation processing in complex systems. Researchers must begin to synthesize knowledge of the unit partsof their study models into relationships and properties that are determined by function of the system as awhole. Advanced computing support databasing services data modeling and knowledge management toolsare essential for this synthesis to occur.The Bioinformatics Biostatistics and Computational Biology (BBCB) Facility Core (hereafter 'Core') willsupport Center investigators with training and services in research design data management statisticalanalysis and computational modeling relevant to environmental genomics and integrative biology. The Corewill function as an interdisciplinary hub to bring together scientific expertise in computer sciences genomicsclinical informatics bioinformatics programming statistics and mathematical modeling. Our overarching goalis to help Center investigators pursue the biology of information processing in living systems from individualpathways to increasingly complex regulatory networks. Toward this end the Core will interact with Centerpersonnel through face to face meetings a dedicated website and specialized tools and services. The SpecificAims are as follows.Aim 1: Provide Center members and Junior investigators with 'Assistance and Support' of research inthe areas of informatics biostatistics and systems modeling.Aim 2: Provide Center investigators students and fellows with 'Education and Training1 on applicationof relevant tools and methods to problems of environmental injury and disease.Aim 3: Promote 'Discovery and Collaboration' to translate research in genomics and integrativebiology into knowledge in environmental health sciences.

project_terms:
Animal Model;Area;Bioinformatics;Biological Models;Biology;Biometry;Collaborations;Collection;Complex;Computational Biology;Computer Simulation;Computer information processing;Core Facility;Daily;Data;Databases;Disease;Educational aspects;Environmental Health;Explosion;Face;Gene Expression;Genetic;Genomics;Goals;Human;Human Resources;Individual;Informatics;Informatics Clinical;Information Resources Management;Injury;Knowledge;Methods;Modeling;Molecular Biology;Numbers;Organism;Pathway interactions;Property;Research;Research Design;Research Personnel;Sampling;Science of Statistics;Services;Signal Transduction;Students;Study models;Support of Research;System;Training;Translating;United States National Institutes of Health;computer science;data management;data modeling;digital;mathematical model;member;programs;repository;response;tool


application_id: 7600360
project_number: 5P30ES014443-02
project_title: Facility Core A: Integrative Health Sciences
administering_ic: NIEHS
application_type: 5
activity_code: P30
ic: ES
serial_number: 014443
study_section: Environmental Health Sciences Review Committee[EHS]
subproject_number: 9001
contact_pi_person_id: 1871961
contact_pi: TOLLERUD, DAVID J
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2008-04-01
budget_end_date: 2009-03-31
funding_mechanism: Research Centers
project_abstract:
The central goal of the Integrative Health Sciences Facility Core (IHSFC) is to provide Center investigators withservices and resources that will facilitate the translation of basic research findings into clinical or public healthapplications. The general goals of the Core are to: Provide services instrumentation and technologies that support the bench-to-bedsidetranslation of basic science findings into clinical and public health applications. Support research to improve early detection prevention and/or therapy for disorders related toenvironmental exposures. Foster partnerships between researchers and community-based organizations and healthagencies that will enhance the development and conduct of clinical and public health research. Educate Center investigators on the nature and requirements of clinical and public healthresearch including ethical legal and social implications  and provide technical support formeeting human subjects HIPAA and other human subjects research requirements. Facilitate clinical or public health-oriented pilot projects. Promote synergistic interactions with the Bioinformatics Biostatistics and ComputationalBiology (BBCB) Facility Core.

project_terms:
Basic Science;Bioinformatics;Biological Markers;Biometry;Clinical;Communities;Computational Biology;Core Facility;Development;Disease;Early Diagnosis;Environmental Exposure;Environmental Health;Fostering;Goals;Health Insurance Portability and Accountability Act;Health Sciences;Housing;Human;Human Subject Research;Nature;Pilot Projects;Prevention;Public Health Applications Research;Research;Research Personnel;Research Project Grants;Resources;Scientist;Services;Support of Research;Technology;Translations;base;bench to bedside;ethical legal social implication;health organization;human subject;improved;instrumentation;member;public health medicine (field)


application_id: 7600359
project_number: 5P30ES014443-02
project_title: Pilot Project Program
administering_ic: NIEHS
application_type: 5
activity_code: P30
ic: ES
serial_number: 014443
study_section: Environmental Health Sciences Review Committee[EHS]
subproject_number: 0003
contact_pi_person_id: 1878918
contact_pi: DARLING, DOUGLAS S
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2008-04-01
budget_end_date: 2009-03-31
funding_mechanism: Research Centers
project_abstract:
OverviewCEGIB will support a Pilot Project Program designed to encourage new and innovative research approacheswith emphasis given to creative new lines of research in environmental genomics and integrative biology. TheProgram will support short-term research projects to enable researchers to collect the data necessary to obtainfunding through governmental and private sector agencies. The primary goal for this program will be todevelop innovative ideas of importance to environmental health sciences. Emphasis will be given to support ofyoung investigators as a tool to launch their research programs and to increase collaborative opportunities withestablished environmental health investigators.\Dr. Douglas S. Darling Associate Professor in the Department of Periodontics Endodontics and DentalHygiene in the School of Dentistry will direct the Center Pilot Project. Dr. Darling is an experienced leader ininternal grant review processes having provided oversight for the Center for Genetics and MolecularMedicine's pilot project efforts for the past three years. He is respected for the high degree of integrity andconfidentiality with which he manages award determinations. He will provide 5% effort to the oversight of thePilot Project Program and service as a member of the Internal Advisory Board. Dr. Darling's researchinterests are in the regulation of gene transcription in eukaryotic cells. His laboratory investigates themolecular mechanism of action of the zfh family of transcription factors. They have isolated cDNA andgenomic clones of the Zinc Finger Homeodomain Enhancer-binding Protein (Zfhep) gene and current projectsare investigating the role of molecular interactions that underlie Zfhep and related genes in earlydevelopment.The Pilot Project Program procedures will function under the following guidelines: A Request for Proposals announcement will be distributed by the CEGIB Administrative Core toUofL investigators and laboratories via electronic and hardcopy flyer distribution and campusbulletin board postings at least 60 days prior to the date of submission. A sample Request forProposals is included with this application. Submitted proposals will be collected by the Administrative Core and forwarded to the PilotProject Committee. The Pilot Project Committee will be chaired by Dr. Douglas Darling and willconsist of four ad hoc members selected by the Center Director for their expertise andrepresentation of all Research Cores. Committee members will be screened for conflict ofinterest that might arise from one or more of the submitted proposals. The Pilot Project Committee will forward the submissions to experts in their appropriate field forexternal scientific merit review. The Committee will conduct an NIH-style review includingconsideration of the external reviews and scores. This information will be used to makerecommendations to the Center Director concerning funding. As directed by the CEGIB Director the Administrative Core staff will prepare a Letter of Awardand will establish accounting access to the awarded funds for the recipients. Projects will be funded for one year. The number and amounts awarded each year may varywith the number of meritorious proposals received and the availability of funds. At least 20%and up to the maximum allowed 25% of the direct cost budget for each year will be designatedfor the Pilot Project Program. Pilot Project recipients will be encouraged to use the CEGIBFacility Cores where they will be afforded the same incentives as CEGIB members.Each Pilot Project recipient will provide a written progress report on his or her projects and willgive an oral presentation to CEGIB members at the annual meeting of the External AdvisoryBoard. Records of the Pilot Project Program will be maintained by the CEGIB Administrative Coreincluding minutes of the Pilot Project Committee meetings reviewer comments accountingrecords written progress reports and copies of all submitted proposals and their outcomes.

project_terms:
Accounting;Award;Binding (Molecular Function);Biology;Budgets;Confidentiality;Conflict of Interest;Core Facility;DNA Complementary;Data;Dental Hygiene;Development;Direct Costs;Electronics;Endodontics;Environmental Health;Eukaryotic Cell;Family;Funding;Genes;Genetic;Genomics;Goals;Grant Review Process;Guidelines;Incentives;Laboratories;Letters;Members Committee;Molecular Mechanisms of Action;Molecular Medicine;Numbers;Oral;Outcome;Periodontic specialty;Pilot Projects;Private Sector;Procedures;Published Comment;Recommendation;Records;Regulation;Reports Progress;Request for Proposals;Research;Research Personnel;Research Project Grants;Role;Sampling;School Dentistry;Score;Services;Transcription Genetic;Writing;Zinc Fingers;day;design;enhancer binding protein;experience;flyer;homeodomain;innovation;interest;member;professor;programs;tool;transcription factor


application_id: 7600358
project_number: 5P30ES014443-02
project_title: Career Development of Environmental Health Investigators
administering_ic: NIEHS
application_type: 5
activity_code: P30
ic: ES
serial_number: 014443
study_section: Environmental Health Sciences Review Committee[EHS]
subproject_number: 0002
contact_pi_person_id: 1886009
contact_pi: PROUGH, RUSSELL ALLEN
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2008-04-01
budget_end_date: 2009-03-31
funding_mechanism: Research Centers
project_abstract:
CAREER DEVELOPMENTSpecific AimsThe Center's Career Development Program will provide training and mentoring for junior basic and clinicalscientists with interests in environmental health sciences with the aim of assisting them in the development ofproductive independent research careers with an emphasis in the environmental health sciences and bringingthem to full Center membership.

project_terms:
Clinical;Development;Environmental Health;Mentors;Program Development;Research;Research Personnel;Scientist;Training;career;interest


application_id: 7600357
project_number: 5P30ES014443-02
project_title: Strategic Vision & Impact on Environmental Health
administering_ic: NIEHS
application_type: 5
activity_code: P30
ic: ES
serial_number: 014443
study_section: Environmental Health Sciences Review Committee[EHS]
subproject_number: 0001
contact_pi_person_id: 6221833
contact_pi: RAMOS, KENNETH S.
other_pis: Not Applicable
congressional_district: 03
department: Unavailable
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2008-04-01
budget_end_date: 2009-03-31
funding_mechanism: Research Centers
project_abstract:
Strategic Vision and Impact on Environmental HealthA. OverviewEnvironmental genomics focuses on the study of the gene-gene and gene-environment interactions thatmediate many of the complex diseases affecting human populations in today's world. This field combines theknowledge derived from modern human and molecular genetics with studies of mRNA protein and metaboliteprofiling to understand how genes and genetic variations interact with environmental factors to cause disease.Integrative biology is a closely related field focused on the application of systems theory to the study ofbiological behavior and pathways critical to the preservation of health or the onset and progression of disease.Advances in the fields of environmental genomics and integrative biology during the past five years have beenfueled by the need to translate molecular knowledge into concepts that impact our day-to-day lives and thatimprove the practice of environmental medicine and public health. To this end University of Louisville (UofL)researchers have implemented academic and research programs in the areas of genetics and molecularmedicine leading to the development of a strong infrastructure in DMA sequencing technologies siRNArepositories transcriptional profiling mass-spectrometry (MS)-based protein analysis and proteomics NMRandMS-based metabolomics and more recently bioinformatics.The establishment of a federally-funded Center for Environmental Genomics and Integrative Biology (CEGIB)at UofL will help environmental health researchers with the management and interpretation of data emergingfrom 'omic technologies and facilitate translation of these findings to public health and clinical practice. Fullrealization of the benefits offered by molecular understanding of gene protein and metabolite expressionprofiles the molecular circuitry that integrates the biological response to environmental injury and theidentification of novel biomarkers of disease will require strong infrastructure support in the areas ofbioinformatics biostatistics computational biology and bench-to-bedside or bench-to-community integration.In this application we seek funding to create a National Institute of Environmental Health Sciences (NIEHS)Core Center at UofL that focuses on the application of genomics and integrative biology to problems inenvironmental health. The UofL Center will promote scientific achievements that advance our molecularunderstanding of human diseases and the role of environmental factors in the pathogenesis of disorders ofcellular growth and differentiation. The thematic areas of scientific focus at UofL are environmentalcardiology environmental carcinogenesis and developmental origins of health and disease. TheseNIEHS-funded areas of scientific activity are ripe for continued expansion and will be greatly facilitated by thecentralized infrastructure promoted by CEGIB. NIEHS investments at UofL will be leveraged by outstandinginstitutional commitments to continue support of core functions in transcriptional profiling proteomics andmetabolomics and to establish clinical and epidemiological research centers. Concerted efforts over the nextfour years will be directed at the integration of disparate datasets to identify gene protein and metabolitenetworks the development of mathematical models to simulate and predict biological behavior and theestablishment of productive partnerships between basic and clinical researchers that advance researchfindings in environmental genomics from the bench to the bedside. These efforts will help UofL environmentalhealth science investigators remain competitive and at the cutting edge of biomedical research.Biological complexity is perhaps nothing more than a reflection of the complexities inherent to the naturalworld. If environmental health researchers are to sustain their impact in advancing the biomedical researchagenda in this country an integrated way of thinking that "marries" molecular biology to the higher levels ofbiological organization needs to be nurtured and cultivated among the environmental health researchcommunity. In this context it is important to recognize that systems level thinking in environmental genomicsis not restricted to biomedical questions but that it crosses over to the domains of clinical medicine and publichealth. Indeed realization of the potential of 'omic technologies will require creation of structures that supportthe research enterprise and advance translation of molecular findings to practice. The team of UofLresearchers assembled in this application can contribute in meaningful ways to this goal.

project_terms:
Achievement;Affect;Area;Behavior;Biochemical Pathway;Bioinformatics;Biological;Biological Markers;Biology;Biomedical Research;Biometry;Cancer Center Support Grant;Cancer Grant Supplements (P30);Cardiology;Cardiovascular Diseases;Clinical;Clinical Medicine;Communities;Community Integration;Complex;Computational Biology;Country;Critical Pathways;Crossing Over Genetic;Data;Data Set;Development;Disease;Disease Progression;Environment;Environmental Health;Environmental Medicine;Environmental Risk Factor;Funding;Gene Proteins;Genes;Genetic;Genomics;Goals;Grants Applications;Health;Health Sciences;Human;Injury;Institutes;Investigation;Investments;Knowledge;Life;Malignant Neoplasms;Mediating;Molecular;Molecular Biology;Molecular Genetics;Molecular Medicine;Molecular Profiling;Pathogenesis;Population;Preservation Biological;Protein Analysis;Proteomics;RNA Messenger;RNA Small Interfering;Recruitment Activity;Research;Research Activity;Research Infrastructure;Research Personnel;Role;Simulate;Spectrum Analysis Mass;Structure;Support of Research;System;Systems Theory;Talents;Technology;Thinking function;Today;Translating;Translations;Universities;Variation (Genetics);Vision;base;bench to bedside;cell growth;concept;day;environmental carcinogenesis;gene environment interaction;human disease;improved;innovation;mathematical model;metabolomics;novel;programs;protein metabolite;public health medicine (field);repository;response


application_id: 7597157
project_number: 5R01DA013425-06
project_title: Naltrexone Prodrugs for Transdermal Delivery
administering_ic: NIDA
award_notice_date: 2009-03-30
application_type: 5
activity_code: R01
ic: DA
serial_number: 013425
program_official: PARK, MOO KWANG
project_start_date: 2002-04-01
project_end_date: 2011-03-31
study_section: Medication Development Research Study Section[NIDA-L]
contact_pi_person_id: 1866585
contact_pi: STINCHCOMB, AUDRA L.
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF PHARMACY
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-04-01
project_abstract:
DESCRIPTION (provided by applicant): Alcoholism and opiate addiction lead to major health-related problems and societal costs for people in the United States and the rest of the world as well. Therefore research and development for improved pharmacologic treatments for drug and alcohol abuse are very important. Naltrexone an opioid antagonist is currently used in oral tablet form to help maintain opioid addicts in a drug-free state. Most recently naltrexone has been indicated as an adjunct in the treatment of alcohol dependence as well as reported to reduce alcohol craving in certain alcoholic populations. Transdermal delivery of naltrexone is desirable for opioid addicts and alcoholics in order to help reduce side effects associated with oral therapy and improve compliance. Naltrexone itself does not have the essential physicochemical properties that would allow a therapeutic dose of the drug to cross the human skin barrier. We plan to continue designing and synthesizing prodrugs which are more skin permeable than naltrexone in order to make a therapeutically successful drug delivery system. We hypothesize that prodrugs of naltrexone and prodrugs in combination with microneedle treatment will improve the transdermal delivery rate of naltrexone and that these prodrugs will make excellent research tools for investigating quantitative structure-permeability relationships (QSPR) for transdermal flux and optimization of flux in combination with microneedle enhancement. These prodrugs/microneedles should improve naltrexone delivery rates across the skin because of optimized physicochemical properties for faster diffusion. The specific aims of this project include: (1) to synthesize a series of naltrexone and naltrexol (active metabolite) prodrugs designed to elucidate fundamental QSPRs for transdermal flux optimization with and without microneedle use (2) to characterize the physicochemical parameters of the drugs including molecular weight molecular volume lipophilicity hydrogen-bonding potentials melting points heats of fusion and solubilities in select solvents (3) to measure the drugs' penetration and concurrent bioconversion through human skin in vitro with and without microneedle use and (4) to characterize the pharmacokinetics of the drugs in guinea pigs in vivo with and without microneedle use. Correlation of our in vitro data with the in vivo model will aid in the creation of a reliable QSPR database for transdermal prodrugs with and without microneedle use as well as help to identify the most promising prodrug/microneedle system for eventual human use.

project_terms:
6 beta-hydroxynaltrexone;Adverse effects;Alcohol abuse;Alcohol dependence;Alcoholism;Cavia;Data;Databases;Diffusion;Dosage Forms;Dose;Drug Delivery Systems;Drug Kinetics;Goals;Heating;Human;Hydrogen Bonding;In Vitro;Knowledge;Lead;Measures;Molecular;Molecular Weight;Naltrexone;Narcotic Antagonists;Opiate Addiction;Opioid;Oral;Penetration;Permeability;Pharmaceutical Preparations;Pharmacotherapy;Plasma;Population;Prodrugs;Property;Recovery;Reporting;Research;Rest;Series;Skin;Solubility;Solvents;Structure;System;Tablets;Therapeutic;United States;alcohol craving;clinical application;cost;craving;design;improved;in vivo;in vivo Model;lipophilicity;melting;problem drinker;research and development;tool


application_id: 7596972
project_number: 5T35DK072923-04
project_title: Summer Endocrine Research Training Program
administering_ic: NIDDK
award_notice_date: 2009-05-04
opportunity_number: PAR-04-090
application_type: 5
activity_code: T35
ic: DK
serial_number: 072923
program_official: PODSKALNY, JUDITH M,
project_start_date: 2006-05-01
project_end_date: 2011-04-30
study_section: Diabetes, Endocrinology and Metabolic Diseases B Study Section[DDK-B]
contact_pi_person_id: 1888054
contact_pi: KLINGE, CAROLYN M.
other_pis: Not Applicable
congressional_district: 03
department: BIOCHEMISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
DESCRIPTION (provided by applicant):  
This proposal describes a short-term summer training program for medical students focused on exposing students to career opportunities in basic and clinical research related to diabetes obesity endocrine disorders metabolic diseases and kidney diseases. This application addresses 2 Specific Aims: Aim 1: To provide hands-on training in basic and clinical Endocrine-based research to medical students in a structured mentored environment. Aim 2: To provide an interactive educational experience that introduces medical students the fundamental skills necessary for basic translational and clinical Endocrine-based research. The training program will include didactic instruction as well as a hands-on-research experience under the direction of a team of experienced basic and clinical research scientists centered on a core of NIDDK-funded investigators and collaborating faculty. These faculty have long-standing success in mentoring medical and graduate students and post-doctoral fellows. Students who have completed at least one year of medical school will be eligible to apply for this 10-week training program. Trainees will be selected based upon their academic performance letters of recommendation and matching their research interests and career goals with suitable mentors. We have been successful in recruiting students from minority rural and economically disadvantaged backgrounds. The students will participate in an established 10-week didactic summer program: "From Bench to Bedside: Introduction to Clinical Research" which included bioethics as well as Endocrine-specific seminars and journal clubs in basic and clinical research. Students will present posters of their research at the end of the program. The training program will begin with six trainees and increase to ten trainees as the program matures. Over the past 6 years the University of Louisville has increased its commitment to health science research and infrastructure graduate education and minority recruitment making this short-term training program for medical students particularly timely

project_terms:
Address;Belief;Bioethics;Career Choice;Clinical;Clinical Medicine;Clinical Research;Clinics and Hospitals;Data;Diabetes Mellitus;Economically Deprived Population;Educational aspects;Endocrine;Endocrine System Diseases;Environment;Faculty;Funding;Goals;Graduate Education;Grant;Hand;Health;Hour;Human;Human Resources;Instruction;Journals;Kidney Diseases;Laboratories;Letters;Medical;Medical Education;Medical Students;Medicine;Mentors;Metabolic Diseases;Minority;National Research Service Awards;Obesity;Participant;Patient Care;Performance;Postdoctoral Fellow;Private Practice;Process;Recommendation;Recruitment Activity;Research;Research Infrastructure;Research Personnel;Research Project Grants;Research Training;Rewards;Rural;Sampling;Scientist;Solutions;Structure;Students;Techniques;Time;Training;Training Programs;Translations;Universities;base;bench to bedside;career;experience;graduate student;health science research;interest;medical schools;meetings;member;peer;posters;programs;response;skills;success;volunteer


application_id: 7596804
project_number: 1S10RR024553-01A1
project_title: Upgrade to Multiuser 3T Magnetic Resonance Imager
administering_ic: NCRR
award_notice_date: 2009-05-02
opportunity_number: PAR-08-036
application_type: 1
activity_code: S10
ic: RR
serial_number: 024553
suffix: A1
program_official: TINGLE, MARJORIE
project_start_date: 2009-05-04
project_end_date: 2010-05-03
study_section: Special Emphasis Panel[ZRG1 SBIB-N (30)]
contact_pi_person_id: 8364843
contact_pi: SMITH, CHARLES DENNIS
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
project_abstract:
DESCRIPTION (provided by applicant): This proposal is for funding to upgrade a high-end 3T Siemens Trio MR imager at the University of Kentucky. The upgrade includes improvements to the gradients the radiofrequency transmitter and receiver systems and data acquisition and reconstruction systems of the imager and will significantly improve the imaging capabilities of the instrument bringing it up to the state-of-the-art and providing a platform for future upgrades. The upgrade is essential to providing continued support for an outstanding group of eleven NIH funded researchers using this instrument as the central piece of experimental apparatus for their neuroscience research into developmental and degenerative diseases such as Parkinson's and Alzheimer's. The rapid development of MR technology and neuroscience research necessitates this upgrade and will position UK researchers to advance research into aging dementia and other neurological diseases. With this upgrade UK neuroscience researchers will have the most sensitive imaging techniques to investigate non-invasively the causes and consequences of neurological diseases. In particular the specific aims of this upgrade are to improve both the speed and signal-to- noise of image acquisition the accuracy of image and spectroscopic measurements and to enable the acquisition of novel diffusion weighted data necessary to explore white matter structure and function. The equipment upgrade will benefit many important cutting-edge research projects such as the development of sensitive tools for early detection of Alzheimer's and Parkinson's diseases understanding the areas of the brain involved in alcoholism and autism and understanding the connection between brain structure and behavior and function. The upgrade supports the long term goal of this group which is the development of methodologies and tools for the study of brain anatomy and function in normal individuals and in subjects affected with neurodegenerative or congenital neurological conditions. The relevance of this equipment upgrade is that it will provide a nationally recognized group of neuroscience investigators with state-of-the-art research tools to greatly expand and enhance their investigations into the changes in the brain and spinal cord which occur with diseases such as Alzheimer's and Parkinson's as well as with normal aging and with therapeutic treatments including biomarkers for these conditions. Expanding this research program is crucial as the techniques developed from non-invasive imaging can easily and rapidly be applied to advancing public health through improved screening and diagnosis.   
PUBLIC HEALTH RELEVANCE: This Shared Instrumentation Grant will upgrade a multi-user high field MR imager to a state-of-the-art instrument for carrying out advanced neuroscience research at the University of Kentucky. The upgrade will add several new acquisition and analysis features to measure through non-invasive imaging the structure and function of the brain. These improvements are essential to continue research into the origin and causes of several neurodegenerative diseases including Parkinson's Alzheimer's Huntington's as well as normal human aging.

project_terms:
Affect;Aging;Alcoholism;Alzheimer's Disease;Anatomy;Area;Arts;Autistic Disorder;Behavior;Brain;Data;Degenerative Disorder;Dementia;Development;Diagnosis;Diffusion;Disease;Early Diagnosis;Equipment;Funding;Future;Goals;Grant;Human;Huntington Disease;Image;Imaging Techniques;Individual;Investigation;Kentucky;Magnetic Resonance;Measurement;Measures;Methodology;Nerve Degeneration;Neurodegenerative Disorders;Neurologic;Neurosciences;Neurosciences Research;Noise;Parkinson Disease;Positioning Attribute;Research;Research Personnel;Research Project Grants;Screening procedure;Signal Transduction;Speed (motion);Spinal Cord;Structure;System;Techniques;Technology;Therapeutic;United States National Institutes of Health;Universities;Weight;biomarker;data acquisition;improved;instrument;instrumentation;nervous system disorder;normal aging;novel;programs;public health medicine (field);public health relevance;radiofrequency;reconstruction;spectroscopic imaging;tool;white matter


application_id: 7596510
project_number: 1R01GM086888-01
project_title: Geometry of gene cophylogenies as relates to genome evolution and speciation
administering_ic: NIGMS
award_notice_date: 2008-07-24
opportunity_number: RFA-GM-08-607
application_type: 1
activity_code: R01
ic: GM
serial_number: 086888
program_official: ECKSTRAND, IRENE A
project_start_date: 2008-08-01
project_end_date: 2013-06-30
study_section: Special Emphasis Panel[ZGM1 CBCB-5 (BM)]
contact_pi_person_id: 9408221
contact_pi: YOSHIDA, RURIKO
other_pis: Not Applicable
congressional_district: 06
department: BIOSTATISTICS & OTHER MATH SCI
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF ARTS AND SCIENCES
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_terms:
Address;Algorithms;Bioinformatics;Biological;Data;Data Set;Derivation procedure;Discipline;Educational Curriculum;Enzymes;Equilibrium;Evolution;Exhibits;Gene Duplication;Gene Transfer Horizontal;Genes;Genome;Genome Human;Informatics;Joints;Learning;Mathematical Biology;Mathematics;Medical;Methods;Modeling;Models Statistical;Molecular Biology;Numbers;Parasites;Phylogenetic Analysis;Polymorphism Genetic;Process;Property;Recording of previous events;Research Personnel;Science;Science of Statistics;Students;System;Techniques;Testing;Training;Trees;base;computer science;concept;design;genome sequencing;heuristics;microbial genome;novel;pathogen;public health medicine (field);software development;tool


application_id: 7595831
project_number: 5P01AG005119-21
project_title: Beta Amyloid and Oxidative Stress in Alzheimer's Disease
administering_ic: NIA
award_notice_date: 2009-04-14
application_type: 5
activity_code: P01
ic: AG
serial_number: 005119
program_official: REFOLO, LORENZO
project_start_date: 1997-05-15
project_end_date: 2013-03-31
study_section: ZAG1-ZIJ-4(O4)
contact_pi_person_id: 1870576
contact_pi: VAN ELDIK, LINDA J
other_pis: Not Applicable
congressional_district: 06
department: OTHER HEALTH PROFESSIONS
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-04-15
project_abstract:
DESCRIPTION (provided by applicant):   Alzheimer's disease (AD) is one of the major health problems in this country and affects over 4.5 million persons. The key to the disease is understanding the pathogenesis of neuron degeneration in specific brain regions so that treatment and prevention can be based on solid data. This application is a resubmission of a competitive renewal of the program project "Beta-Amyloid and Oxidative Stress in AD" (P01 AG05119-20) by the Sanders-Brown Center on Aging at the University of Kentucky (UK). Abundant evidence indicates that free radical mediated oxidative damage in the brain is prominent in AD especially in the earliest detectable clinical phase of AD - mild cognitive impairment (MCI). The major hypothesis of this application is that beta amyloid peptide (A) is one of the pivotal mechanisms in oxidative stress/damage to neurons in AD. The proposal consists of three cores including 1) an Administrative Core that provides supervision fiscal management biostatistical support and database management clinical and neuropathological data and brain specimens from the UK AD Center 2) a unique Beta-Amyloid Core that will provide the A index (total p^o and AM2 A solubility oligomeric and fibrillar A  quantitation and plaque quantitation) from human subjects and transgenic mice and also will provide toxic assembled A  and non-toxic scrambled A  for cell culture experiments and 3) an Animal Core that will supply APP/PS1 knock-in mutant mice and WT mice and primary rodent cortical neuron cultures for projects. Each project uses short postmortem brain specimens from longitudinally followed preclinical AD (PCAD) MCI late AD normal controls and frontotemporal dementia (as a disease control) subjects APP/PS1 transgenic mice and cell cultures and each has a therapeutic component and excellent preliminary data to support their hypotheses.   
  
Project 1 examines the hypothesis that brain RNA oxidation is an early event in AD and is mediated at least in part by A and that the RNA oxidation impairs protein synthesis and contributes to neuron dysfunction. Project 2 examines the hypothesis that A -mediated oxidative modifications of and subsequent dysfunction of Pin1 are fundamental to the genesis of specific pathological features in AD. Project 3 will examine the hypothesis that elevations in RAGE-ligand interactions occur in AD with soluble RAGE modulating A assembly and toxicity. Project 4 examines the hypothesis that sustained activation of NADPH oxidase by toxic forms of AP triggers a cascade linking increased ROS to altered redox-based signaling and neurotoxic oxidative damage. This well integrated program project will move the field of A and oxidative stress in AD forward and gain insights into mechanisms of neuron degeneration so that successful interventions can be developed to treat or prevent the most dehumanizing disorder to affect humans.


application_id: 7591795
project_number: 5R01DA017711-05
project_title: Stimulant Abuse Pharmacotherapy: Novel Antipsychotics
administering_ic: NIDA
award_notice_date: 2009-04-20
application_type: 5
activity_code: R01
ic: DA
serial_number: 017711
program_official: OVERSBY, STEVEN
project_start_date: 2005-08-01
project_end_date: 2011-04-30
study_section: ZDA1-RXL-E(07)
contact_pi_person_id: 1888410
contact_pi: RUSH, CRAIG R
other_pis: Not Applicable
congressional_district: 06
department: PSYCHOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-05-01
project_abstract:
DESCRIPTION (provided by applicant):  Methamphetamine abuse is a significant public-health concern and is the primary form of amphetamine abused in the United States. Between 1996 and 2002 the number of Americans that reported using methamphetamine increased by 250%. Amphetamine admissions to treatment program increased by nearly 500% between 1992 and 2002. Methamphetamine use made up 90% of all amphetamine treatment admissions. Because of the public-health concerns identifying an effective pharmacotherapy for the management of methamphetamine dependence is imperative. Methamphetamine is thought to exert its. behavioral effects by promoting the release of several monoamines including dopamine (DA) serotonin (5- HT) and norepinephrine (NE) which has prompted some theoreticians to suggest targeting multiple systems for the development of a pharmacotherapy. Partial agonists at these neurotransmitter systems may represent a novel and effective means to treat stimulant dependence. In support of this notion partial agonists at D2 and 5-HT1A receptors attenuate many of the behavioral effects of amphetamines in laboratory animals In the present application we propose a series of experiments to determine the efficacy of iripiprazole an atypical antipsychotic that is a D2 and 5-HT1A partial agonist and a 5-HT2A antagonist as a putative pharmacotherapy for methamphetamine dependence. The results of a recent experiment conducted in our laboratory suggest that aripiprazole significantly attenuates the discriminative-stimulus and some of the positive subjective effects of d-amphetamine in humans. The present project has three specific aims. The first specific aim is to characterize the behavioral pharmacology of methamphetamine in humans. The second specific aim is to assess the safety and tolerability of methamphetamine in combination with aripiprazole. The third specific aim is to determine the efficacy of aripiprazole as a putative pharmacotherapy by examining the discriminative-stimulus reinforcing and subjective effects of methamphetamine in humans following chronic pretreatment with aripiprazole. The proposed research will provide initial scientific and clinical information regarding the use of aripiprazole as a pharmacotherapy for the treatment of methamphetamine dependence and guide the design of future clinical trials.

project_terms:
Admission activity;Adverse effects;Affinity;Age;Agonist;American;Amphetamine Abuse;Amphetamines;Animals;Antipsychotic Agents;Attenuated;Basic Science;Behavioral;Binding (Molecular Function);Buprenorphine;Chronic;Clinical;Clinical Trials;Cocaine;Computer Systems Development;Data;Dependence;Development;Dextroamphetamine;Discrimination (Psychology);Dopamine;Dose;Epidemiology;Future;Gender;HTR2A gene;Human;Individual;Individual Differences;Laboratories;Laboratory Animals;Maintenance;Measures;Mediating;Methamphetamine;Methylphenidate;Movement Disorders;Neurotransmitters;Norepinephrine;Opiate Addiction;Opioid;Patients;Pharmaceutical Preparations;Pharmacotherapy;Procedures;Prolactin;Psychostimulant dependence;Questionnaires;Receptor Serotonin 5-HT1A;Recording of previous events;Reporting;Research;Research Personnel;Safety;Series;Serotonin;Serum;Socioeconomic Status;Specificity;Stimulus;System;Tail;United States;aripiprazole;atypical antipsychotic;behavior measurement;behavioral pharmacology;cocaine use;design;drug discrimination;effective therapy;improved;methamphetamine abuse;monoamine;motor control;novel;programs;public health medicine (field);receptor;research study;serotonin receptor;stimulant abuse;treatment program


application_id: 7591477
project_number: 1R01AA018016-01
project_title: The Role of Alcohol in HIV Therapy Hepatotoxicity
administering_ic: NIAAA
award_notice_date: 2008-09-29
opportunity_number: RFA-AA-08-013
application_type: 1
activity_code: R01
ic: AA
serial_number: 018016
program_official: WANG, JOE
project_start_date: 2008-09-30
project_end_date: 2013-08-31
study_section: Special Emphasis Panel[ZAA1 BB (02)]
contact_pi_person_id: 1902075
contact_pi: MCCLAIN, CRAIG J.
other_pis: BARVE, SHIRISH S;EATON, JOHN W
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_terms:
Acetaminophen;Acidosis Lactic;Acquired Immunodeficiency Syndrome;Affect;Alcohol abuse;Alcohol consumption;Alcoholic Liver Diseases;Alcohols;Anti-HIV Agents;Anti-HIV Therapy;Anti-Retroviral Agents;Antiretroviral Therapy Highly Active;CD4 Positive T Lymphocytes;CYP2E1 gene;Caspase Inhibitor;Cause of Death;Chronic;Class;Clinical;Combination Drug Therapy;Combivir;Communicable Diseases;Delavirdine;Depressed mood;Development;Didanosine;Disease;Disease Progression;Drops;Drug Interactions;Elevation;Enrollment;Enzymes;Fatty Liver;Functional disorder;Gilead brand of tenofovir disoproxil fumarate;Goals;Grant;HIV;HIV Infections;HIV therapy;Health;Hepatic;Hepatitis;Hepatitis B Virus;Hepatitis C;Hepatitis C virus;Hepatocyte;Hepatology;Hepatotoxicity;Histology;Human;Hypersensitivity;Immune;In Vitro;Incidence;Indinavir;Infection;Injury;Insulin Resistance;Invasive;Killings;Lamivudine;Lamivudine/Zidovudine;Life Expectancy;Lipodystrophy;Liver;Liver Failure Acute;Liver diseases;Lopinavir/Ritonavir;Lymphocyte Count;Lymphocyte Depletion;Measures;Mediating;Metabolic;Metabolism;Mitochondria;Morbidity - disease rate;Mortality Vital Statistics;Mus;Names;Nelfinavir;Nevirapine;Nucleosides;Nucleotides;Numbers;Outcome;Oxidative Stress;Patients;Pharmaceutical Preparations;Pneumonia;Population;Predisposition;Principal Investigator;Production;Protease Inhibitor;Proteasome Inhibition;Proteins;Range;Reaction;Reporting;Research;Reverse Transcriptase Inhibitors;Risk;Ritonavir;Roche brand of pentafuside;Role;S-Adenosylmethionine;Saquinavir;Saquinavir Mesylate;Screening procedure;Series;Severities;Simulate;Site;Stavudine;Symptoms;T-20;TNF gene;TNF protein human;Technology;Tenofovir;Testing;Therapeutic Intervention;Time;Toxic effect;Trizivir;Tuberculosis;Tumor Necrosis Factor-alpha;Tumor Necrosis Factors;United States National Institutes of Health;Universities;Viral hepatitis;Work;World Health Organization;Zalcitabine;abacavir;alcohol effect;analog;antiretroviral therapy;base;caspase;cohort;crixivan;cytokine;design;efavirenz;emtricitabine;epivir;experience;feeding;fosamprenavir;high risk behavior;immune function;inhibitor/antagonist;interest;mitochondrial dysfunction;multicatalytic endopeptidase complex;non-nucleoside reverse transcriptase inhibitors;novel;programs;prospective;public health medicine (field);reconstitution;sustiva;tipranavir;translational approach;truvada;viracept


application_id: 7591152
project_number: 5T35ES014559-04
project_title: Summer Environmental Health Sciences Training Program
administering_ic: NIEHS
award_notice_date: 2009-04-01
application_type: 5
activity_code: T35
ic: ES
serial_number: 014559
program_official: SHREFFLER, CAROL A
project_start_date: 2006-04-01
project_end_date: 2011-03-31
study_section: Environmental Health Sciences Review Committee[EHS(TB)]
contact_pi_person_id: 1886009
contact_pi: PROUGH, RUSSELL ALLEN
other_pis: Not Applicable
congressional_district: 03
department: BIOCHEMISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-04-01
project_abstract:
This proposal describes a short-term summer training programfor medical students focused on exposing students to career opportunities in basic and clinical research related to environmental health sciences.This application addresses 2 Specific Aims: Aim 1: To provide hands-on training in basic and clinical Environmental Health Sciences-based researchto medical students in a structured mentored environment.Aim 2: To provide an interactive educational experience that introduces medical students the fundamentalskills necessary for basic translational and clinical Environmental Health Sciences-based research. The training program will include didactic instruction as well as a hands-on-research experience under thedirection of a team of experienced basic and clinical researchscientists centered on a core of NIEHS-funded investigators and collaborating faculty. These faculty have long-standing success inmentoring medical and graduate students and post-doctoral fellows. Students who have completed at leastone year of medical school will be eligible to apply for this 10-weektraining program. Trainees will beselected based upon their academic performance letters of recommendation and matching their researchinterests and career goals with suitable mentors. We have been successful in recruiting students fromminority rural and economically disadvantaged backgrounds. The students will participate in anestablished 10-week didactic summer program: "From Bench to Bedside: Introduction to Clinical Research"which included bioethics as well as Environmental Health Sciences-specific seminars and journal clubs inbasic and clinical research. Students will present posters of their research at the end of the program. Thetraining program will begin with six trainees and increase toten trainees as the program.matures. Over thepast 6 years the University of Louisville has increased its commitment to health science research andinfrastructure graduate education and minority recruitment making this short-term training program formedical students particularly timely. . \

project_terms:
Address;Belief;Bioethics;Career Choice;Clinical;Clinical Medicine;Clinical Research;Economically Deprived Population;Educational aspects;Environment;Environmental Health;Faculty;Funding;Goals;Graduate Education;Grant;Hand;Health;Human;Instruction;Journals;Letters;Medical;Medical Education;Medical Students;Medicine;Mentors;Minority;National Institute of Environmental Health Sciences;National Research Service Awards;Patient Care;Performance;Postdoctoral Fellow;Private Practice;Process;Recommendation;Recruitment Activity;Research;Research Infrastructure;Research Personnel;Research Training;Rewards;Rural;Structure;Students;Training;Training Programs;Translations;United States National Institutes of Health;Universities;base;bench to bedside;career;experience;graduate student;health science research;interest;medical schools;posters;programs;response;skills;success


application_id: 7590885
project_number: 1R03CA137801-01
project_title: Prevention of reflux-induced esophageal adenocarcimona by dietary berries
administering_ic: NCI
award_notice_date: 2008-09-18
opportunity_number: PAR-08-055
application_type: 1
activity_code: R03
ic: CA
serial_number: 137801
program_official: SEIFRIED, HAROLD E
project_start_date: 2008-09-19
project_end_date: 2010-08-31
study_section: Special Emphasis Panel[ZCA1 SRLB-F (O1)]
contact_pi_person_id: 7674642
contact_pi: MARTIN, ROBERT C
other_pis: Not Applicable
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
DESCRIPTION (provided by applicant):  
  
Esophageal adenocarcinoma (EAC) has the fastest rate of increase among all cancers in America yet there is very little research on the mechanisms and prevention of its development. EAC primarily affects White males and has one of the poorest prognoses among all cancers. Barrett's esophagus (BE) is a pre-cancerous lesion associated with the development of EAC. BE is caused by chronic heartburn which affects more than 19 million Americans every year. Pharmaceutical treatments to cure heartburn do not appear to largely affect EAC incidence. New intervention strategies are urgently needed to address this issue. Commonly available berries such as blueberries (BB) and black raspberries (BRB) are natural chemopreventative agents that can be easily incorporated into the American diet and used for clinical intervention. Moreover dietary BRBs are highly effective in preventing squamous cell carcinoma (SCC) another type of esophageal cancer the incidence of which is declining. We have developed an animal model that mimics the clinical development of EAC. In this model chronic esophageal reflux resembling heartburn is induced in rats using a surgical procedure. More than one-third of the rats develop EAC at the end of 6 months. We can effectively use this model to study the preventive efficacy of dietary berries. Two types of berries have been chosen since they differ widely in their phytochemical profiles. Our objective is to study the efficacy of dietary berries to prevent the development of reflux-induced EAC and to understand the mechanisms by which they do so. To achieve this we plan to provide BB and BRB via the diet to male rats at a dose of 2.5% which is equivalent of consuming one-half cup of dried berries every day. We will surgically-induce chronic reflux. At the end of 6 months the rats that were provided with berry diet will be compared with those that did not receive intervention to evaluate the incidence of tumors. To further understand the mechanisms by which berries may prevent esophageal tumorigenesis we plan to use intermediary monthly time points during the development of EAC to study the biomarkers that are altered. The first set of biomarkers deal with oxidative stress and will determine whether berries can induce cellular antioxidant enzymes such as superoxide dismutase catalase and glutathione peroxidase which ultimately protect the cells from oxidative damage. Lipid peroxidation and oxidative DNA damage will be used as markers of oxidative stress. The second set of biomarkers deal with inflammation associated with BE. Nuclear factor kappa B (NF?B) a transcription factor that controls the expression of several cancer-inducing genes is found to be activated by inflammation in BE. We will evaluate whether berries can prevent this activation. Thus by following a two-part approach we will be able to determine whether berries prevent EAC progression and the mechanisms involved in this prevention.

project_terms:
8-Oxo-2'-Deoxyguanosine;Address;Adenocarcinoma;Adverse effects;Affect;American;Americas;Anastomosis - action;Animal Model;Animals;Antioxidants;Barrett Esophagus;Berry;Biological Assay;Biological Markers;Biology;Blueberries;Cancerous;Carcinogens;Cells;Chemoprevention;Chemopreventive Agent;Chronic;Clinical;DNA Damage;Development;Diet;Dietary Supplements;Dose;Enzyme-Linked Immunosorbent Assay;Enzymes;Epithelium;Esophageal;Esophageal Adenocarcinoma;Esophageal carcinoma;Esophageal mucous membrane;Esophagitis;Etiology;Forecast of outcome;Gastroesophageal reflux disease;Genes;Heartburn;Immunoblot Analysis;Incidence;Inflammation;Inflammatory;Intervention;Lesion;Lipid Peroxidation;Longitudinal Studies;Malignant Neoplasms;Malignant Squamous Cell Neoplasm;Malignant neoplasm of esophagus;Manganese Superoxide Dismutase;Measures;Microscopic;Modeling;Molecular;Mortality Vital Statistics;NF-kappa B;National Cancer Institute;Operative Surgical Procedures;Oxidative Stress;Pathway interactions;Peptic Esophagitis;Pharmacologic Substance;Phytochemical;Polymerase Chain Reaction;Prevention;Preventive;Randomized;Raspberries;Rate;Rattus;Reflux;Reporting;Research;Squamous cell carcinoma;Staining method;Stains;Stress;Superoxide Dismutase;Survival Rate;Time;Week;Work;base;cancer diagnosis;catalase;cyclooxygenase 2;day;falls;glutathione peroxidase;male;oxidative DNA damage;prevent;transcription factor;tumor;tumorigenesis

public_health_relevance:
Project NarrativeBarrett's esophagus (BE) is a pre-cancerous lesion associated with the development of esophagealadenocarcinoma the fastest growing cancer among Americans. We propose to use an animal model of BE tostudy the preventive effects of 2 types of dietary berries (blueberries and black raspberries) on EAC incidence.


application_id: 7589657
project_number: 5R01EY016724-04
project_title: Neuroplasticity Genes in Visual Cortex
administering_ic: NEI
award_notice_date: 2009-03-26
application_type: 5
activity_code: R01
ic: EY
serial_number: 016724
program_official: ARAJ, HOUMAM H
project_start_date: 2006-04-01
project_end_date: 2012-03-31
study_section: Central Visual Processing Study Section[CVP]
contact_pi_person_id: 1868720
contact_pi: MOWER, GEORGE D
other_pis: Not Applicable
congressional_district: 03
department: ANATOMY/CELL BIOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-04-01
project_abstract:
The goal of this proposal is to identify candidate genes controlling neuroplasticity (CPGs) in visual cortex.Dark rearing slows the entire time course of the visual cortical critical period and therefore provides a meansto dissociate changes associated with the state of plasticity from changes associated with maturation. A'differential display PCR screening by this laboratory of all of the expressed genes in the visual cortex ofnormal and dark reared cats at 5 and 20 weeks identified 23 CPGs. CPGs fall into 2 classes: "plasticity"'genes whose expression is enhanced in age/rearing conditions where neuroplasticity is maximal and "anti-plasticity" genes whose expression is opposite. One novel CPG that was identified is Mund3-3 ("anti-plasticity") which plays an essential role in vesicle release at glutamatergic synapses. A novel "plasticity"CPG is disabled-1 (Dab-1) a gene that plays a central role in the migration of cortical neurons. The projectwill address the following specific aims: 1. To test the hypothesis that CPG gene mutation will alter the timecourse of the physiologically defined critical period in mouse visual cortex. Electrophysiological andimmediate early gene expression methodologies will determine the effect of Mund3-3 and Dab-1 mutationon susceptibility to monocular deprivation. 2. To test the hypothesis that "plasticity" and "anti-plasticity" CPGswill show distinct temporal associations with known laminar specific developmental events during the criticalperiod in visual cortex. In situ hybridization and immunohistochemistry will be used to compare "plasticity"and "anti-plasticity" gene/protein expression in layer IV and extragranular visual cortical layers as a functionof age and dark rearing. 3. To verify the identity of previously unsuspected CPGs indicated by the genescreen. Our screen has implicated novel CPGs with documented neurological functions. In addition toMund3-3 and Dab-1 Plasticity Related Gene 1 (PRG-1) which influences axonal outgrowth and two genesassociated with Ras mediated cytoskeletal reorganization (Chimaerinl and Abl interacting protein 2) aretentatively identified. The identification of effector genes which control the visual cortical critical period wouldbe a major step in unraveling molecular mechanisms of neuronal plasticity. Such information is essential tounderstanding processes such as neuronal development regeneration learning and memory and wouldfurther open the possibility of manipulation of nervous system neuroplasticity for therapeutic benefit.

project_terms:
Actins;Address;Age;Animals;Biological;Candidate Disease Gene;Cytoskeletal Modeling;Darkness;Development;Event;Felis catus;Gene Expression;Gene Mutation;Gene Proteins;Genes;Glutamates;Goals;Gold;Immediate-Early Genes;Immunohistochemistry;In Situ Hybridization;In-Migration;Laboratories;Learning;Mediating;Memory;Messenger RNA;Methodology;Methods;Mitochondria;Modeling;Molecular;Mus;Mutant Strains Mice;Mutation;Natural regeneration;Nervous System Physiology;Nervous system structure;Neuronal Plasticity;Neurons;Northern Blotting;Ocular dominance columns;Physiological;Play;Predisposition;Process;Proteins;Relative (related person);Research Personnel;Role;Screening procedure;Synapses;Synaptic Vesicles;Testing;Therapeutic;Time;Vesicle;Visual Cortex;Western Blotting;Work;base;critical developmental period;critical period;dark rearing;falls;mRNA Differential Displays;migration;monocular deprivation;mutant;neuron development;normal aging;novel;postnatal;programs;protein expression


application_id: 7589011
project_number: 1K99HL087924-01A2
project_title: Granule exocytosis and neutrophil activation
administering_ic: NHLBI
award_notice_date: 2009-02-18
opportunity_number: PA-07-297
application_type: 1
activity_code: K99
ic: HL
serial_number: 087924
suffix: A2
program_official: MONDORO, TRACI
project_start_date: 2009-03-01
project_end_date: 2011-02-28
study_section: Special Emphasis Panel[ZHL1 CSR-Z (O1)]
contact_pi_person_id: 8652094
contact_pi: URIARTE, SILVIA M
other_pis: Not Applicable
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
project_abstract:
DESCRIPTION (provided by applicant):   
  
The postulated role of exocytosis in mediating various functional responses associated with neutrophil activation has not been directly tested. We will use a novel approach; generating TAT-fusion proteins containing the coiled-coil domains of different SNARE proteins; to test the hypothesis that blocking exocytosis of distinct granule subsets will prevent specific neutrophil phenotypic changes and this strategy may be used to prevent neutrophil-mediated tissue damage in vivo. The specific objectives of the mentored phase of this proposal are: 1) to determine the ability of TAT-fusion proteins containing the SNARE domains of SNAP-23 syntaxins and VAMPs to inhibit exocytosis of each of the four neutrophil granule subsets. The training goal of this aim is to develop molecular biology and cell biology skills that will allow the applicant to address experimental questions at new levels and apply them in the independent phase of this proposal. 2) To determine the most effective way to administer the TAT-SNARE fusion proteins in vivo and to determine the effect of these fusion proteins on models of acute neutrophil-dependent inflammation in rats. The training goals of this aim are to learn animal models of neutrophil-dependent inflammation and to establish the ability of TAT-fusion proteins to inhibit neutrophil exocytosis in vivo. 3) Define other proteins that interact with SNARE proteins by proteomic analysis. The training goal of this aim is to develop the ability to perform proteomic analysis. The state-of-the-art techniques acquired during the mentored phase will greatly increase the expertise that will allow the PI to become a successful independent investigator. For the independent phase the specific objectives are: 1) To determine the specific functional responses that are regulated by neutrophil granule exocytosis; 2) To define the mechanisms by which inhibition of neutrophil exocytosis in vivo blocks the inflammatory response; and 3) To investigate the molecular mechanisms by which exocytosis is stimulated. The training the applicant will receive will make her unique in the combination of experience interest and state-of-the-art technology and will maximize her potential to become an independent NIH-funded investigator. (End of Abstract)

project_terms:
Acute;Address;Adherence (attribute);Air;Animal Model;Arts;C-terminal;Cell membrane;Cellular biology;Chemotaxis;Chimeric Proteins;Coiled-Coil Domain;Computer software;Cytoplasmic Granules;Data;Databases;Docking;Event;Exocytosis;Funding;Gelatinases;Generations;Goals;Human;Immunoprecipitation;Inflammation;Inflammatory Response;Intracellular Membranes;Killings;Learning;Lung Injury Acute;Mass Spectrum Analysis;Mediating;Membrane;Membrane Fusion;Membrane Protein Traffic;Mentors;Methodology;Modeling;Molecular;Molecular Biology;N-terminal;Natural Immunity;Neutrophil Activation;Normal tissue morphology;Peptide Hydrolases;Peptides;Phagocytosis;Phase;Phosphorylation;Plasmids;Post-Translational Protein Processing;Proteins;Proteomics;Rattus;Reactive Oxygen Species;Regulation;Research Personnel;Respiratory Burst;Role;SNAP receptor;Secretory Vesicles;Site;State Interests;Stimulus;Techniques;Technology;Tertiary Protein Structure;Testing;Tissues;Training;Vesicle;abstracting;base;effusion;experience;extracellular;in vitro testing;in vivo;neutrophil;novel strategies;prevent;receptor;response;skills;syntaxin


application_id: 7588034
project_number: 5R21AA016307-02
project_title: Neurogenesis and neurodegeneration in adolescent binge alcohol exposure
administering_ic: NIAAA
award_notice_date: 2009-02-17
opportunity_number: PA-06-181
application_type: 5
activity_code: R21
ic: AA
serial_number: 016307
program_official: BAIZER, LAWRENCE
project_start_date: 2008-03-20
project_end_date: 2011-02-28
study_section: Biomedical Research Study Section[AA-1]
contact_pi_person_id: 1869834
contact_pi: NIXON, KIMBERLY
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF PHARMACY
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
DESCRIPTION (provided by applicant): Adolescence is a time when many individuals begin to experiment with alcohol. Alcohol abuse and alcohol dependence collectively termed alcohol use disorders are diagnosed in ~6% of adolescents and result in significant neuropsychological and/or cognitive deficits. As many as half of all high school students may currently drink alcohol and up to 70% of those students are binge drinkers. Considering that binge drinking is one of the factors that predicts brain damage from alcohol understanding the impact of binge drinking on adolescent brain structure is an important public health concern. The neuroanatomical consequences of adolescent drinking are not well described though two studies have shown hippocampal volume reductions in adolescents with alcohol use disorders. This finding confirmed behavioral and neurophysiological work in animal models that the adolescent hippocampus is targeted by alcohol. However no one has examined whether alcohol directly produces neurodegeneration in the adolescent rat or the basic mechanism of cell or neuron reduction. The recent discovery that neural stem cells contribute to ongoing neurogenesis and to hippocampal structure suggests a novel potential mechanism of neurodegeneration alcohol-induced  
neurodegeneration. Thus this application will test the overall hypothesis that binge alcohol exposure in the adolescent rat alters neural stem cells and neurogenesis to produce neurodegeneration. Three specific aims will address this hypothesis in an in vivo rat model of an adolescent alcohol use disorder by (1) investigating the effects of adolescent binge alcohol administration on the components of neurogenesis (2) determining the mechanism by which alcohol intoxication inhibits neural stem cell proliferation and (3) evaluating whether changes in neurogenesis are associated with neurodegeneration (net reduction of cells) in the hippocampal dentate gyrus. Within each aim important questions regarding the contribution of alcohol dose or duration necessary to alter the components of neurogenesis and the contribution of cell death will be investigated. Understanding the mechanism of alcohol-induced effects on neural stem cells and dentate gyrus granule cell loss forms a solid foundation to investigate the differential sensitivity of the adolescent brain to alcohol effects and the dynamic role of both cell death and cell birth mechanisms in neurodegeneration.

project_terms:
Acute;Address;Adolescence;Adolescent;Adult;Alcohol abuse;Alcohol consumption;Alcohol dependence;Alcoholic Intoxication;Alcohols;Animal Model;Area;Behavioral;Birth;Blood alcohol level measurement;Brain;Brain Injuries;Cell Cycle;Cell Death;Cell Death Inhibition;Cell Differentiation process;Cell Proliferation;Cell Survival;Cells;Chemistry;Chronic;Cognitive deficits;Data;Diagnosis;Dose;Ethanol;Exploratory/Developmental Grant;Fibrinogen;Foundations;Future;Generations;Hippocampus (Brain);Human;Impairment;Individual;Killings;Modeling;Mosses;Nerve Degeneration;Neurons;Process;Publishing;Rattus;Research;Rodent Model;Role;Solid;Stem cells;Structure;Students;Testing;Time;Tissues;Uridine;Work;adolescent alcohol exposure;adolescents with alcohol use disorders;adult neurogenesis;alcohol effect;alcohol exposure;alcohol use disorder;base;binge drinker;binge drinking;cognitive function;cooking;dentate gyrus;experience;granule cell;high school;in vivo;mature animal;migration;nerve stem cell;neurogenesis;neuron loss;neurophysiology;neuropsychological;novel;problem drinker;public health medicine (field);research study;stem cell population;underage drinking


application_id: 7587318
project_number: 5R01AT002890-03
project_title: Novel Herbal Medicine for the Treatment of Prostate Cancer
administering_ic: NCCIH
award_notice_date: 2009-03-12
application_type: 5
activity_code: R01
ic: AT
serial_number: 002890
program_official: HOPP, CRAIG
project_start_date: 2007-04-01
project_end_date: 2011-05-31
study_section: Chemo/Dietary Prevention Study Section[CDP]
contact_pi_person_id: 7649061
contact_pi: DAMODARAN, CHENDIL
other_pis: Not Applicable
congressional_district: 06
department: OTHER CLINICAL SCIENCES
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCH ALLIED HEALTH PROFESSIONS
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-04-01
project_abstract:
DESCRIPTION (provided by applicant): Prostate cancer (PCa) is the second leading cause of cancer-related deaths among men in the U.S. and many western countries. Although early diagnosis of PCa has improved significantly in recent years there is a need for more effective treatment strategies for patients presenting with advanced or metastatic disease. Earlier we reported that the chloroform fraction of Rasagenthi Lehyam (cRL) an herbal preparation is effective for the treatment of PCa (Ranga et al. 2004). In subsequent studies we identified the most potent compound (cRL-CI: psoralidin) from the cRL fraction which exhibited more potent anti-cancer effects in PCa cells compared to other isolated components from the cRL fraction. We found that cRL-CI inhibited cell viability and induced apoptosis in PC-3 and DU-145 cells. Additional studies of cRL-CI revealed (i) induction of G2/M arrest of cell cycle (ii) inhibition of NFkB activation (iii) alteration of Bcl2/Bax proteins and (iv) activation of caspase signaling in cell culture models of PCa. In addition in vivo xenograft assays substantiate these in vitro findings and show that cRL-CI inhibits prostate tumor growth in nude mice. Interestingly our results demonstrate that cRL-CI specifically targets cancer cells without causing significant toxicity to normal prostate epithelial cells. Although these results suggest cRL-CI alters molecular signaling its effect on inhibition of pro-survival mechanisms activation of pro-apoptotic signaling and cell cycle arrest are not well understood. Our proposed aims will not only delineate these potential mechanisms of action but will also address the pre-clinical evaluation of cRL-CI against PCa cells. Based on our preliminary studies we hypothesize that cRL-CI will effectively suppress the growth of PCa due to its ability to inactivate NFkB and IAP signaling induce cell cycle arrest and initiate caspase-mediated apoptosis in PCa. This hypothesis will be tested by the following specific aims using in vitro and in vivo approaches. Aim 1. Study the mechanism(s) of NFkB inhibition in PCa by cRL-CI. Aim 2. Elucidate the role of inhibition of apoptosis (lAPs) family proteins in cRL-CI induced apoptosis in PCa cells. Aim 3.Investigate the molecular mechanism(s) for cRL-CI -induced cell cycle arrest in PCa cells. Aim 4.Explore the anti-tumor activity of cRL-CI in animal models. The proposed studies will define the mechanism by which cRL-CI inhibits growth of PCa cells and may lead to the identification of mechanism-based biomarkers. Additionally the results from the proposed studies can be exploited to develop chemotherapeutic and/or chemoprevention strategies for PCa thus leading to clinical trials to determine the efficacy of the cRL-CI against PCa.

project_terms:
Address;Adenocarcinoma;Animal Model;Apoptosis;Apoptotic;BCL2 gene;BIRC4 gene;Bax protein;Biological Assay;CDC2 Protein Kinase;Cancer Etiology;Cell Culture Techniques;Cell Cycle;Cell Cycle Arrest;Cell Survival;Cells;Cessation of life;Chemoprevention;Chloroform;Clinical Trials;Country;Data;Disease;Early Diagnosis;Epithelial Cells;Event;Exhibits;G2/M Arrest;G2/M Transition;Gene Expression;Gene Targeting;Growth;Herbal Medicine;In Vitro;Inhibition of Apoptosis;Lead;M cell;Malignant Neoplasms;Malignant neoplasm of prostate;Mediating;Modeling;Molecular;Mus;Nude Mice;Oral Administration;Pathway interactions;Patients;Pattern;Phosphorylation;Phosphotransferases;Plant Preparations;Prostate;Prostatic Neoplasms;Protein Family;Proto-Oncogene Proteins c-akt;Radiation therapy;Reporting;Research Personnel;Resistance;Role;Signal Transduction;Stream;Tail;Testing;Toxic effect;Transgenic Organisms;Tumor Tissue;Veins;Xenograft procedure;base;biomarker;cancer cell;caspase;chemotherapy;effective therapy;improved;in vivo;insight;men;novel;pre-clinical;psoralidin;research clinical testing;research study;survivin;synaptotagmin I;treatment strategy;tumor;tumor growth


application_id: 7586234
project_number: 5R01AI067869-03
project_title: YopM and protective innate defenses against plague
administering_ic: NIAID
award_notice_date: 2009-02-25
opportunity_number: PA-04-119
application_type: 5
activity_code: R01
ic: AI
serial_number: 067869
program_official: MUKHOPADHYAY, SUMAN
project_start_date: 2007-03-16
project_end_date: 2012-02-29
study_section: Host Interactions with Bacterial Pathogens Study Section[HIBP]
contact_pi_person_id: 1864206
contact_pi: STRALEY, SUSAN C
other_pis: Not Applicable
congressional_district: 06
department: MICROBIOLOGY/IMMUN/VIROLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
DESCRIPTION (provided by applicant): Yersinia pestis the causative agent of plague delivers a set of 6 Yop toxins that act within host cells to negate and modulate signaling pathways that orchestrate host innate defenses that are crucial for developing an effective immune response. This proposal focuses on the mechanism of YopM. We have found that YopM specifically causes a global loss of natural killer cells and those NK cells remaining do not contain detectable mRNA for IFNg. Concomitantly YopM causes down-regulation in macrophages of net mRNA expression for key proinflammatory cytokines. In this project we will test the hypothesis that YopM acts directly on cells such as macrophages and dendritic cells to prevent expression of cytokines such as IL- 15 and IL-12 that synergize to activate effector cells such as macrophages polymorphonuclear neutrophils natural killer cells and cytolytic T cells for controlling numbers of Y. pestis. In Aim 1 we will determine whether YopM's action is mediated by hypothesized key cells by comparing the infection dynamics for virulent and YopM- Y. pestis (viable numbers dissemination as a function of time) and host response (cell populations and cytokines) in primary pneumonic plague and bubonic plague in mice ablated for the cells genetically or by manipulation. In Aim 2 we will test our hypothesis that the Th1 cytokine and chemokine pathway mediates different host responses to YopM+ and YopM- Y. pestis between d 1 and d 3 to 4 p.i. in bubonic and pneumonic plague by infecting knockout mice or mice ablated for hypothesized key cytokines and analyzing the resulting infection dynamics and host response. In Aim 3 we will map the signaling circuitry of YopM's pathogenic effects by comparing transcriptional profiles (cDNA microarrays) and analyses of intracellular cytokines in purified macrophages from mice with pneumonic or bubonic plague due to virulent and YopM- Y. pestis. The data will reveal the pathogenic mechanism of YopM by identifying cells cytokines and signaling pathways modulated by YopM during plague. The findings will provide a completely new understanding of the biology of plague from both microbial and host perspectives as well as provide a framework for rational enhancement of resistance to plague in people threatened with exposure to plague. The data will reveal immune deviation points during plague and could identify potential therapeutic intervention targets. The findings also will provide a better understanding of mammalian innate defenses and insight into evasive mechanisms of pathogens and will facilitate the defeat of important human pathogens that are not select agents.

project_terms:
Biology;CD8B1 gene;Cells;Classification;Cytokine Signaling;Cytotoxic T-Lymphocytes;Data;Dendritic Cells;Down-Regulation;Effector Cell;Exposure to;Foundations;Human;Immune;Immune response;Infection;Interleukin-1;Interleukin-12;Interleukin-15;Interleukin-18;Knockout Mice;Lung;Maps;Mediating;Messenger RNA;Mus;Natural Killer Cells;Parents;Pathway interactions;Plague;Pneumonic Plague;Population;Predictive Value;Reporting;Resistance;Signal Pathway;Signal Transduction;Spleen;T-Lymphocyte;Testing;Therapeutic Intervention;Time;Toxin;Virulence;Virulent;Yersinia pestis;cDNA Arrays;chemokine;cytokine;insight;mRNA Expression;macrophage;microbial host;mouse model;mutant;neutrophil;pathogen;prevent;research study


application_id: 7586180
project_number: 5R01DK080418-02
project_title: Adiponectin and Regulation of Triglyceride Metabolism
administering_ic: NIDDK
award_notice_date: 2009-02-04
opportunity_number: PA-07-070
application_type: 5
activity_code: R01
ic: DK
serial_number: 080418
program_official: LAUGHLIN, MAREN R
project_start_date: 2008-04-01
project_end_date: 2009-06-30
study_section: Skeletal Muscle and Exercise Physiology Study Section[SMEP]
contact_pi_person_id: 8333955
contact_pi: SHAO, JIANHUA
other_pis: Not Applicable
congressional_district: 06
department: NUTRITION
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
DESCRIPTION (provided by applicant): Adiponectin is an adipose-derived hormone that promotes insulin sensitization and plays an important role in energy metabolism. However adiponectin gene expression and plasma adiponectin concentrations are paradoxically reduced in obesity. Hypertriglyceridemia usually accompanies adiposity. Previous human and animal studies have clearly shown that circulating adiponectin protein levels correlate inversely with triglyceride concentrations indicating that adiponectin regulates triglyceride metabolism. However the mechanism by which adiponectin regulates triglyceride metabolism is largely unknown. Our long term goal is to elucidate the underlying mechanisms of obesity-induced dyslipidemia. Using adenovirus-mediated in vivo gene transduction we have shown that elevated plasma adiponectin reduces serum triglyceride levels without significantly changing hepatic very low density lipoprotein (VLDL)-triglyceride production. Interestingly post-heparin plasma lipoprotein lipase (LPL) activities as well as LPL and VLDL receptor gene expression in skeletal muscle were significantly increased in mice with elevated plasma adiponectin. LPL is a rate-limiting enzyme for VLDL- triglyceride hydrolysis and the VLDL receptor enhances LPL activity. Our studies have also found that the expression of PPAR3 co-activator-11 (PGC-11) was robustly increased by adiponectin in both skeletal muscle and cultured myotubes. PGC-11 plays a pivotal role in skeletal muscle mitochondrial biogenesis and fatty acids oxidation. Therefore we hypothesize that adiponectin reduces plasma triglyceride concentration by increasing VLDL-triglyceride catabolism in skeletal muscle and that PGC-11 mediates the regulatory effects of adiponectin by increasing LPL and VLDLr gene expression. This project will address two main specific aims. In specific aim 1 we will investigate the mechanism by which adiponectin stimulates VLDL-triglyceride catabolism and the roles of skeletal muscle LPL and the VLDLr in this regulation. This will be accomplished in part using skeletal muscle tissue-specific LPL-deficient or VLDLr-deficient mice. In addition the role of the LKB1/AMPK pathway in adiponectin-stimulated VLDL-TG catabolism in skeletal muscle will be investigated using skeletal muscle-specific LKB1-deficient mice. In specific aim 2 we will use the PGC-11-deficient mice and molecular techniques to determine the mechanisms by which PGC-11 mediates adiponectin-induced VLDL-triglyceride catabolism in skeletal muscle. This study is expected to reveal a new mechanism and concept about how an adipose-derived hormone adiponectin regulates lipid and lipoprotein metabolism. It will also shed light on a novel mechanism that integrates adipose and skeletal muscle tissues in the context of lipoprotein metabolism. These studies may lead to new prevention or therapeutic strategies for obesity and the metabolic syndrome which impose a serious health problem world wide. PUBLIC HEALTH RELEVANCE: This study is expected to reveal a new mechanism and concept about how an adipose-derived hormone adiponectin regulates lipid and lipoprotein metabolism. It will also shed light on a novel mechanism that integrates adipose and skeletal muscle tissues in the context of lipoprotein metabolism. These studies may lead to new prevention or therapeutic strategies for obesity and the metabolic syndrome which impose a serious health problem world wide.

project_terms:
Address;Adenoviruses;Adipocytes;Adipose tissue;Animals;Atherosclerosis;Biogenesis;Cardiovascular Diseases;Catabolism;Cells;Coronary Arteriosclerosis;Couples;Development;Diet;Dyslipidemias;Energy Metabolism;Enhancers;Enzymes;Fatty Acids;Fatty acid glycerol esters;Gene Expression;Genes;Glucose;Goals;Health;Heparin;Hepatic;High Density Lipoprotein Cholesterol;Hormones;Human;Hydrolysis;Hypertriglyceridemia;Insulin;Lead;Light;Lipids;Lipoproteins;Mediating;Metabolic syndrome;Metabolism;Mitochondria;Modeling;Molecular;Mus;Muscle Cells;Muscle Fibers;Nonesterified Fatty Acids;Obesity;Peroxisome Proliferator-Activated Receptors;Plasma;Play;Prevention;Production;Proteins;Receptor Gene;Regulation;Reporting;Research;Risk Factors;Role;Serum;Skeletal muscle structure;Small Interfering RNA;Techniques;Therapeutic;Tissues;Transduction Gene;Transgenic Mice;Transgenic Organisms;Triglyceride Metabolism;Triglycerides;Up-Regulation (Physiology);VLDL receptor;Very low density lipoprotein;adiponectin;base;biomarker;fatty acid oxidation;in vivo;insulin signaling;lipid metabolism;lipoprotein lipase;mouse model;novel;oxidation;receptor expression;very low density lipoprotein triglyceride


application_id: 7586126
project_number: 5P01HL080100-04
project_title: Mechanisms of abdominal aortic aneurysm formation
administering_ic: NHLBI
award_notice_date: 2009-03-29
application_type: 5
activity_code: P01
ic: HL
serial_number: 080100
program_official: GOLDBERG, SUZANNE H
project_start_date: 2006-04-08
project_end_date: 2011-03-31
study_section: Heart, Lung, and Blood Program Project Study Section[HLBP]
contact_pi_person_id: 8378256
contact_pi: DAUGHERTY, ALAN
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-04-01
project_abstract:
DESCRIPTION (provided by applicant):    This amended PPG application is designed to provide mechanistic insight into the mechanisms involved in the initiation and propagation of abdominal aortic aneurysms (AAAs). Projects will use a model of AAA in which angiotensin II will be infused into hyperlipidemic mice. This was described originally by faculty who are Project Leaders in this application. This model has now been adopted widely in both academic and pharmaceutical research programs. Many characteristics of the model reproduce features of the human disease including the strong gender specific prevalence in males fragmentation of medial extracellular matrix and presence of inflammatory cells. Studies on the cellular sequence of events in the development of AAAs demonstrate the involvement of inflammatory cells at all stages of development. The unifying hypothesis of this amended program project application is that angiotensin II promotes aneurysm formation by initiating regional-specific matrix degradation in the media of the abdominal aorta leading to recruitment of macrophages medial dissection and subsequent vascular remodeling. Four projects are proposed that mechanistically define the sequence of events outlined in this unifying hypothesis. To facilitate research among Projects 4 core facilities are proposed. This brings together a group of faculty who have interacted for several years. The synergy of their interactions is demonstrated by the multiple joint publications and co-investigator status on grants. These projects and cores have been designed to provide mechanistic insight into the development of AAAs in the following areas: Project 1 (Lisa A. Cassis) will study the role of male androgen in promoting regional-specificity of AAA formation through regulation of the angiotensin type 1A receptor. Project 2 (Alan Daugherty) will determine the role of smooth muscle cell specific AT1a receptors in the mechanisms of AAA initiation. Project 3 (Fred C. de Beer) will determine the role of serum amyloid A and its interaction with selected matrix metalloproteinases. Project 4 (Nancy R. Webb) will determine the role of specific isoenzymes of secretory phospholipase A2s in promoting inflammation at the site of macrophage recruitment during the evolving AAA. These projects will be supported by Cores of: A. Administration. B. Human studies. C. Mouse maintenance. D. Quantitative pathology.


application_id: 7586125
project_number: 5P01HL080100-03
project_title: CORE--Mouse
administering_ic: NHLBI
application_type: 5
activity_code: P01
ic: HL
serial_number: 080100
study_section: Heart, Lung, and Blood Program Project Study Section[HLBP]
subproject_number: 9002
contact_pi_person_id: 8817787
contact_pi: RATERI, DEBRA
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2008-04-01
budget_end_date: 2009-03-31
funding_mechanism: Non-SBIR/STTR
project_abstract:
The purpose of this Core is to provide a central location for the supply of mice and services related to mouse
care maintenance genotyping and measurement. Specifically this Core will offer the following services:
1. Managing the mouse colony that includes the oversight of the generation maintenance and supply of
single and compound genetically altered mice.
2. Perform bone marrow transplantation.
3. Measure arterial blood pressure in a standardized manner.
4. Prepare and implant Alzet pumps for the infusion of Angll or saline.
5. Harvest DNA by tail clipping for the purpose of genotyping.
6. In vivo ultrasound. Non-invasively quantify lumen diameter during the evolution of AAAs.
Centralization of these facilities will permit an efficient use of resources for the Program coupled with optimal
quality control and standardization across Projects.

project_terms:
Blood Pressure;Bone Marrow Transplantation;Caliber;Caring;Clip;Coupled;DNA;Evolution;Generations;Genotype;Harvest;Implant;Infusion Pumps;Location;Maintenance;Measurement;Measures;Mus;Purpose;Quality Control;Resources;Saline;Services;Standardization;Tail;Ultrasonography;in vivo;programs


application_id: 7586124
project_number: 5P01HL080100-03
project_title: CORE--Human Studies
administering_ic: NHLBI
application_type: 5
activity_code: P01
ic: HL
serial_number: 080100
study_section: Heart, Lung, and Blood Program Project Study Section[HLBP]
subproject_number: 9001
contact_pi_person_id: 7332137
contact_pi: MUKHERJEE, DEBABRATA
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2008-04-01
budget_end_date: 2009-03-31
funding_mechanism: Non-SBIR/STTR
project_abstract:
The purposesof this Core is to begin to translate findings from experimental studies in the individual projects
examining Angll-induced AAAs to human AAAs. Specifically this Core will offer the following services:
1. A tissue bank of human AAAs for immunohistochemical analysis of mediators under study in the
individual projects.
2. Sera plasma and DNA samples from the AAA Cohort and the Health In Men Study from the Western
Australia Abdominal Aortic Aneurysm Study (WA AAAS). These samples will be used to examine the
relationship between plasma concentrations of molecules of interest genotypes and aortic diameter.
3. Statistical analysis of serum concentrations and aortic diameter odds ratios and 95% confidence intervals
to estimate the relative risk of either aortic diameter or rate of expansion with concentration of the mediator.
4. Cardiovascular imaging to noninvasively examine AAAs and their relationship to proposed plasma
measurements.
Establishment of this Core with recognized Clinician Scientists to supervise translational studies as well as
samples from an NIH funded study focused on a unique AAA population will permit translation of
experimental studies to human AAAs.

project_terms:
Aortic Aneurysm Abdominal;Caliber;Confidence Intervals;DNA;Funding;Genotype;Health;Human;Individual;Measurement;Mediator of activation protein;Odds Ratio;Plasma;Population;Rate;Risks Relative;Sampling;Scientist;Serum;Services;Tissue Banks;Translating;Translations;United States National Institutes of Health;Western Australia;cardiovascular imaging;cohort;human study;interest;men;research study;translational study


application_id: 7586123
project_number: 5P01HL080100-03
project_title: Specific Secretory Phospholipase A2 Isozymes Promote Aneurysm Formation
administering_ic: NHLBI
application_type: 5
activity_code: P01
ic: HL
serial_number: 080100
study_section: Heart, Lung, and Blood Program Project Study Section[HLBP]
subproject_number: 0003
contact_pi_person_id: 7875305
contact_pi: WEBB, NANCY R
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2008-04-01
budget_end_date: 2009-03-31
funding_mechanism: Non-SBIR/STTR
project_abstract:
Secretory phospholipase A2 enzymes (sPLA2's) in particular the Group HA Group V and Group X
subtypes have been implicated in a wide variety of inflammatory diseases. We provide evidence that
sPLA2s play a role in promoting abdominal aortic aneurysm (AAA) formation in a mouse model of this
vascular disease. An sPLA2 inhibitor of broad specificity profoundly reduces both the incidence and severity
of Angiotensin II (Angll)-induced AAAs in apoE-/- mice. Additionallly transgenic mice expressing human
Group IIA sPLA2 have increased susceptibility to Angll-induced AAAs compared to non-transgenic mice.
The central hypothesis of this proposal is that Group IIA Group V and/or Group X sPLA2 expressed by
macrophages infiltrating into the vessel wall accelerate AAA formation by promoting the localized release of
inflammatory prostanoids. This hypothesis is based on published data and our own preliminary findings that:
a) macrophage infiltration into the medial layer of the abdominal aorta is an early event in AAAs; b) Group V
and Group X sPLA2 protein are present in AAAs in apoE-/- mice c) the aortic expression of Group V and
Group X sPLA2 mRNA is increased in apoE-/- mice infused with Angll; d) these isozymes are expressed by
macrophages; e) these isozymes have been implicated in cyclooxygenase 2 (COX-2)-dependent prostanoid
production; and f) mice treated with a COX-2-selective inhibitor have significantly reduced AAAs in response
to chronic Angll infusion. To test this hypothesis we propose to identitify specific sPLA2(s) mediating AAA
progression and define the relative contribution of leukocyte expression of these sPLA2 isozymes in its
pathogenic effect (Specific Aim 1); define the relative contribution of systemic versus leukocyte-expressed
Group IIA sPLA2 in mediating Angll-induced AAAs (Specific Aim 2); and determine whether the pathogenic
effect of sPLA2 is dependent on COX-2 activity (Specific Aim 3). These studies hold the potential to identify
a new target for AAA intervention.

project_terms:
Abdomen;Abdominal aorta structure;Affect;Aneurysm;Angiotensin II;Animal Model;Aorta;Aortic Aneurysm;Aortic Aneurysm Abdominal;Apolipoprotein E;Arachidonic Acids;Blood Circulation;Blood Vessels;Bone Marrow Transplantation;Cardiovascular system;Cells;Chronic;Coronary Arteriosclerosis;Coupling;Data;Deposition;Development;Disease;Eicosanoids;Elastin Fiber;Enzymes;Event;Extracellular Matrix;Gene Targeting;Generations;Grants Applications;Human;Incidence;Infiltration;Inflammation;Inflammatory;Infusion procedures;Intervention;Isoenzymes;Lead;Leukocytes;Localized;Medial;Mediating;Mice Transgenic;Mus;Pathology;Phospholipase A2;Plasma;Play;Predisposition;Process;Production;Program Research Project Grants;Prostaglandin Production;Prostaglandin-Endoperoxide Synthase;Prostaglandins;Proteins;Publishing;RNA Messenger;Relative (related person);Research Personnel;Risk Factors;Role;Serum;Severities;Site;Specificity;Testing;Thinking function;Tissues;Transgenes;Transgenic Organisms;Vascular Diseases;base;cell type;cyclooxygenase 1;cyclooxygenase 2;group V secretory phospholipase A2;group X secretory phospholipase A(2);in vivo;inhibitor/antagonist;interest;macrophage;mouse model;programs;response;sPLA2 enzyme


application_id: 7586122
project_number: 5P01HL080100-03
project_title: Smooth Muscle Cell AT1a Receptor in Initiating Events in AAAs
administering_ic: NHLBI
application_type: 5
activity_code: P01
ic: HL
serial_number: 080100
study_section: Heart, Lung, and Blood Program Project Study Section[HLBP]
subproject_number: 0002
contact_pi_person_id: 8378256
contact_pi: DAUGHERTY, ALAN
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2008-04-01
budget_end_date: 2009-03-31
funding_mechanism: Non-SBIR/STTR
project_abstract:
We propose a central hypothesis that Angll initiates AAA formation through smooth muscle cell AT1 receptor
activation regulating the LRP-uPAR axis to promote medial macrophage accumulation. To test this
hypothesis we propose the following specific aims: Aim>1: Determine the contribution of smooth muscle
cell-specific AT1a receptors to AAA production and cellular changes in the aorta. The effects of smooth
muscle cell specific AT1a receptor deficiency on AAA development will be determined in Angll-infused LDL
receptor -/- mice. We will use AT1a receptor floxed mice in which smooth muscle cell deficiency will be
accomplished with Cre expressed under the control of SM22. The effect of smooth muscle cell AT1a
receptor deficiency will be determined on the cellular changes that occur in the initiating phase of AAA
development. Aim 2: Determine the role of Angll on regulation of LRP in smooth muscle cells and the effect
of reduced LRP on susceptibility to AAA development. We will determine the mechanisms by which Angll
downregulates LRP. This will be performed in cultured smooth muscle cells derived from specific aortic
regions. We will determine if mice that are hypomorphic for LRP are more susceptible to Angll-induced
AAAs. This will be performed in mice that are deficient in RAP the molecular chaperone of LRP. Aim 3:
Determine the contribution of uPAR to the development of Angll-induced AAAs. We will use uPAR -/- mice
to determine its role in development of Angll-induced AAAs. "Forward" and "reverse" bone marrow
transplantation studies will determine the tissue loci of uPAR involved in Angll-induced AAAs. Aim 4:
Determine the origin of medial macrophages accumulated in the aorta during Angll-infusion. Bone marrow
transfer studies with mice expressing allelic variants of CD45 will be used to define whether Angll-induced
accumulation of macrophages in the aortic layers originate from blood-borne monocytes or resident
macrophages in the adventitia of the aorta.

project_terms:
Abdomen;Aneurysm;Angiotensin II;Aorta;Aortic Aneurysm Abdominal;Apolipoprotein E;Arterial Fatty Streak;Atherosclerosis;Blood;Blood Vessels;Bone Marrow;Bone Marrow Transplantation;Cell surface;Cells;Characteristics;Chest;Development;Disease;Dissection;Event;Genotype;Infiltration;Infusion procedures;LDL-Receptor Related Protein 1;Link;Lipoprotein Receptor;Low Density Lipoprotein Receptor;Medial;Molecular Chaperones;Mus;Myocytes Smooth Muscle;PTPRC gene;Pathology;Phase;Plasminogen Activator;Predisposition;Production;Protein Deficiency;Proteins;Proteolysis;Receptor Activation;Regulation;Research Personnel;Role;Stimulus;Testing;Thick;Tissues;Tunica Adventitia;Urokinase;Variation (Genetics);base;cell type;macrophage;migration;monocyte;programs;receptor


application_id: 7586121
project_number: 5P01HL080100-03
project_title: Androgen Regulation of Angiotensin Responses in Aneurysms
administering_ic: NHLBI
application_type: 5
activity_code: P01
ic: HL
serial_number: 080100
study_section: Heart, Lung, and Blood Program Project Study Section[HLBP]
subproject_number: 0001
contact_pi_person_id: 1857999
contact_pi: CASSIS, LISA A
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: Domestic Higher Education
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2008-04-01
budget_end_date: 2009-03-31
funding_mechanism: Non-SBIR/STTR
project_abstract:
Male gender is one of the strongest risk factors in the development of abdominal aortic aneurysms (AAAs).
Our results demonstrate a 3-fold greater incidence of angiotensin II (Angll)-induced AAAs in male ApoE-/-
mice compared to females. Ovariectomy did not influence Angll-induced AAAs. In contrast orchiectomy
reduced AAA incidence to the level observed in females. These results demonstrate that male sex
hormones mediate gender differences in Angll-induced AAAs. Additional data demonstrate greater Angll
receptor density and responsiveness in the abdominal aorta of male than female mice. We hypothesize that
during development androgen localizes the AT1a receptor to vascular smooth muscle cells of the abdominal
aorta of male mice and continues to increase AT1a receptor expression in cell types critical to the formation
of AAAs in adult male mice. In Specific Aim 1 we will determine the temporal effect of exogenous
testosterone administration on AAA formation and localization. The effect of exogenous testosterone in
orchiectomized male and in female mice on Angll-induced AAAs will be determined. A focus will be on
regulation of the AT1a receptor in the abdominal aorta of male1 and female mice administered testosterone.
In Specific Aim 2 we will determine the cell type mediating androgen receptor effects on AAA formation.
The effect of whole body androgen receptor deficiency on Angll-induced AAAs will be examined in male
mice. Since macrophages and smooth muscle are involved early in Angll-induced AAAs we will determine
the effect of deficiency of androgen receptors on bone marrow-derived cells and on smooth muscle on Angllinduced
AAAs. Additional studies will define mechanisms for androgen regulation of the AT1a receptor
promoter. In Specific Aim 3 we hypothesize that in utero developmental effects of androgen on the
mesenchyme give rise to AT1a receptors on vascular smooth muscle cells of the abdominal aorta in adult
male mice thereby localizing AAAs to this region. We will determine the effect of androgen ablation in utero
in males and testosterone administration to neonatal female mice on Angll-induced AAAs in adult offspring.
Results from these studies will identify mechanisms for gender differences in AAA formation.

project_terms:
Abdomen;Abdominal aorta structure;Ablation;Adult;Adult Children;Age;Androgen Receptor;Androgens;Aneurysm;Angiotensin II;Angiotensins;Aorta;Aortic Aneurysm;Aortic Aneurysm Abdominal;Apolipoprotein E;Area;Atherosclerosis;Blood Vessels;Bone Marrow;Cardiovascular Diseases;Cells;Chest;Chronic;Clinical;Data;Development;Dissection;Event;Exhibits;Female;Gender;Genes;Genetic;Gonadal Steroid Hormones;Human;Incidence;Infusion procedures;Length;Localized;Low Density Lipoprotein Receptor;Medial;Mediating;Mesenchymal;Mesenchyme;Molecular;Mus;Myocytes Smooth Muscle;Neonatal;Numbers;Orchiectomy;Ovariectomy;Promotor (Genetics);Regulation;Research;Research Personnel;Risk Factors;Role;Series;Sex Characteristics;Smooth muscle (tissue);Stem cells;Testicular Hormones;Testosterone;Thinking function;cell type;density;in utero;macrophage;male;programs;receptor;receptor binding;receptor density;receptor expression;response


application_id: 7585084
project_number: 2R01GM047915-14A1
project_title: Modified Photoproteins as Labels and Molecular Switches in Bioanalysis
administering_ic: NIGMS
award_notice_date: 2009-01-12
opportunity_number: PA-07-070
application_type: 2
activity_code: R01
ic: GM
serial_number: 047915
suffix: A1
program_official: EDMONDS, CHARLES G
project_start_date: 1995-01-01
project_end_date: 2012-11-30
study_section: Instrumentation and Systems Development Study Section[ISD]
contact_pi_person_id: 1964876
contact_pi: DAUNERT, SYLVIA
other_pis: CAMMERS, ARTHUR
congressional_district: 06
department: CHEMISTRY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF ARTS AND SCIENCES
organization_zip: 405260001
organization_country: UNITED STATES
project_abstract:
DESCRIPTION (provided by applicant): Continuous discoveries in bioengineering and more efficient molecular biology methods have allowed scientists to create new designer biomolecules with unique and distinct properties. In that regard bio- nanotechnology and nanoscale analysis are becoming increasingly prevalent raising the demand for techniques with high sensitivity that can detect biomolecules in biological samples. Bioluminescent photoproteins such as aequorin possess great potential to provide with a solution to this new challenge because they can be detected at low concentrations and have different emission wavelengths depending on the protein variant used a property that can be exploited in multiplex analysis. We now propose to prepare new aequorin variants to broaden the scope of their use in bioanalysis thus allowing for detection of biomolecules that are not detectable by other technologies. Protein molecular switches with optical properties are another type of designer biomolecules that in the presence of a target ligand demonstrate an altered response manifested by an "on/off" signal. These molecules can be useful in a variety of applications such as in the development of nanosensors for in vitro and in vivo detection. To that end we plan to design and develop bioluminescent molecular switches that incorporate the recognition properties of binding proteins with the bioluminescence afforded by the aequorin variants. The hypotheses formulated for the proposed work are based on knowledge gained during our current funding period and investigate the use of a series of computational and synthetic approaches along with genetic engineering strategies targeting the alteration of the electronic environment of the chromophore that should lead to new bioluminescent proteins and molecular switches with a wide range of spectral properties. These photoproteins will be employed in the development of assays for important biomolecules. Finally we will investigate the use of the newly prepared bioluminescent molecular switches in the multiplex analysis of biomolecules and in the simultaneous analysis of molecules in single cells. We anticipate that the new photoproteins will provide with new enabling technologies for in vitro and in vivo biosensing imaging and multiplex analysis that have a number of advantages over existing methods.  
  
PUBLIC HEALTH RELEVANCE: NARRATIVE The increasing importance of nanoscale analysis has raised the demand for highly sensitive systems that can detect biomolecules in biological samples. Bioluminescent photoproteins such as aequorin possess great potential to provide a solution to this new challenge because they can be detected at very low concentrations in physiological fluids. In that regard we plan to design and prepare genetically modified photoproteins that form the basis of enabling technologies for the detection of relevant biomolecules and panels of biomarkers for in vitro and in vivo applications.

project_terms:
Aequorin;Affect;Amber;Amino Acid Sequence;Amino Acids;Apoproteins;Binding (Molecular Function);Binding Proteins;Biological;Biological Assay;Bioluminescence;Biomedical Engineering;Biosensing Techniques;Biotechnology;Categories;Cells;Characteristics;Codon Nucleotides;Computer Analysis;Detection;Development;DsRed;Electronics;Engineering;Environment;Family;Funding;Genetic Code;Genetic Engineering;Goals;Half-Life;Hydrogen Bonding;Image;In Vitro;Knowledge;Label;Lead;Libraries;Life;Ligands;Liquid substance;Living Wills;Luciferases;Luminescent Proteins;Methods;Microfluidics;Molecular;Molecular Biology;Nanotechnology;Optics;Peptide Sequence Determination;Performance;Physiological;Play;Post-Translational Protein Processing;Preparation;Property;Protein Binding Domain;Proteins;Protocols documentation;Research;Resolution;Role;Sampling;Scaffolding Protein;Scheme;Scientist;Series;Signal Transduction;Site;Solutions;Source;Structure;System;Techniques;Technology;Time;Variant;Work;analog;assay development;base;biomarker;chromophore;coelenterazine;computer studies;design;directed evolution;hybrid protein;in vivo;luminescence;molecular recognition;mutant;nanoscale;nanosensors;obelin;protein structure;public health relevance;response;scaffold;tool

public_health_relevance:
NARRATIVEThe increasing importance of nanoscale analysis has raised the demand for highlysensitive systems that can detect biomolecules in biological samples. Bioluminescentphotoproteins such as aequorin possess great potential to provide a solution to thisnew challenge because they can be detected at very low concentrations in physiologicalfluids. In that regard we plan to design and prepare genetically modified photoproteinsthat form the basis of enabling technologies for the detection of relevant biomoleculesand panels of biomarkers for in vitro and in vivo applications.


application_id: 7584055
project_number: 5R01CA102102-05
project_title: BIOSYNTHETIC KEY STEPS OF ANGUCYCLINE ANTITUMOR DRUGS
administering_ic: NCI
award_notice_date: 2009-04-10
application_type: 5
activity_code: R01
ic: CA
serial_number: 102102
program_official: FU, YALI
project_start_date: 2005-05-01
project_end_date: 2011-03-31
study_section: Bio-Organic and Natural Products Chemistry Study Section[BNP]
contact_pi_person_id: 2257319
contact_pi: ROHR, JURGEN T
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF PHARMACY
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-04-01
project_abstract:
DESCRIPTION (provided by applicant): Gilvocarcins and jadomycins are angucyclin-derived anticancer drugs/antibiotics possessing unique molecular frames whose common biosynthetic key step is an oxidative rearrangement catalyzed by a closely related set of enzymes.   
  
The gilvocarcins produced by various Streptomyces strains including Streptomyces griseoflavus Go 3592 represent a distinct family of interesting aryl C-glycoside antitumor drugs with a coumarin-based aromatic core that promote specific DNA interactions when photoactivated by near UV light. This class of anticancer drugs shows excellent antitumor activity and remarkably low toxicity. Its unprecedented molecular architecture in conjunction with its unique biological activity makes the gilvocarcins an excellent target for biosynthetic studies and the development of novel photoactivatable anticancer drugs through combinatorial biosynthesis. The drugs may be useful for the treatment of special cancers such as brain tumors colon skin lung and prostate cancers or leukemia. The jadomycins are antibiotics/antifungals whose structure is characterized by an unusual insertion of an amino acid building block after an oxidative bond breakage.  
  
Previous biosynthetic studies suggest for both gilvocarcins and jadomycins a pathway dominated by a type-2 polyketide synthase (PKS) leading initially to an angucycline type drug intermediate which then oxidatively rearranges into the final molecular frame. Selected intriguing post-PKS tailoring steps namely the oxidative rearrangement (gilvocarcin and jadomycin biosynthesis) the unusual C-glycosylation step (gilvocarcin biosynthesis) and the formation of the vinyl group side chain of gilvocarcin V are key biosynthetic features responsible for the generation of structural elements which are essential for the unique biological activity of the gilvocarcin drugs. The investigation of these cascades of post-PKS tailoring biosynthetic key reactions found in both the jadomycin and gilvocarcin biosyntheses is a main goal of the research since it as an interesting model for post-PKS enzyme complexes their mechanisms interactions substrate binding/passing modes etc. This topic has never been studied in detail despite the importance of such tailoring steps for the biological activity of polyketide drugs. The understanding of these biosynthetic steps and the enzymes responsible for their execution will ultimately pave the way for the generation of more potential and more selective drugs through combinatorial biosynthetic methods. The following specific aims will be addressed: (1) Characterization of the late steps of the gilvocarcin and jadomycin biosynthesis; (2) Generation of new gilvocarcin analogues by inactivation and recombination of selected post-PKS tailoring genes; (3) Characterization of key enzymes of the gilvocarcin and the related jadomycin biosynthetic pathway to understand their mechanism-of-action and substrate specificity range their interaction; and (4) assessment of the antitumor activity of gilvocarcin and newly generated analogues from specific aim 2. The long-term goal of this research is to develop improved anticancer drugs for the treatment of special cancers.

project_terms:
Address;Amino Acids;Anabolism;Antifungal Antibiotics;Antineoplastic Agents;Architecture;Binding (Molecular Function);Biological;Brain;Brain Neoplasms;C-glycoside;Colon;Coumarins;DNA;DNA Sequence Rearrangement;Development;Elements;Enzymatic Biochemistry;Enzymes;Family;Figs - dietary;Foundations;Gene Cluster;Generations;Genes;Genetic Recombination;Goals;Histones;Investigation;Knowledge;Lead;Lung;Malignant Neoplasms;Malignant neoplasm of prostate;Methods;Modeling;Modification;Molecular;Multienzyme Complexes;Oxygenases;Pathway interactions;Pharmaceutical Preparations;Production;Property;Prostate;Reaction;Research;Route;Side;Skin;Streptomyces;Streptomyces lividans;Structure;Substrate Interaction;Substrate Specificity;Toxic effect;Ultraviolet Rays;alpha benzopyrone;analog;anticancer activity;antineoplastic antibiotics;antitumor drug;base;combinatorial;drug biological activity;gilvocarcin V;glycosylation;glycosyltransferase;improved;interest;jadomycin B;leukemia;mutant;novel;polyketide synthase


application_id: 7583885
project_number: 1R01EY018830-01A1
project_title: MerTK regulation of the PTTG and RPE phagocytosis
administering_ic: NEI
award_notice_date: 2008-09-19
opportunity_number: PA-07-070
application_type: 1
activity_code: R01
ic: EY
serial_number: 018830
suffix: A1
program_official: MARIANI, ANDREW P
project_start_date: 2008-09-30
project_end_date: 2013-08-31
study_section: Biology and Diseases of the Posterior Eye Study Section[BDPE]
contact_pi_person_id: 8875628
contact_pi: LU, QINGXIAN
other_pis: Not Applicable
congressional_district: 03
department: OPHTHALMOLOGY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
project_terms:
Adult;Affect;Apoptotic;Autoimmune Diseases;Blindness;Candidate Disease Gene;Cell Nucleus;Cells;DNA Sequence Rearrangement;Data;Defect;Degenerative Disorder;Distal;Ectopic Expression;Epithelium;Failure (biologic function);Family;Fibroblast Growth Factor 2;Functional disorder;Gene Expression Profile;Gene Expression Profiling;Gene Expression Regulation;Gene Targeting;Genes;Goals;Homeostasis;Human;IL8 gene;In Vitro;Ingestion;Inherited;Investigation;Knock-out;Knowledge;Lymphocyte;MERTK protein human;Measurement;Mediating;Metaphase;Mice Knockout;Mice Mutant Strains;Mitosis;Modeling;Molecular;Morphology;Mus;Mutation;One-Step dentin bonding system;PTTG1 gene;Patients;Phagocytes;Phagocytosis;Phenotype;Photoreceptors;Physiological;Pigments;Preservation Biological;Prevalence;Protein Overexpression;Protein Tyrosine Kinase;RNA Interference;Rattus;Recovery of Function;Regulation;Retina;Retinal;Retinal Degeneration;Retinitis Pigmentosa;Rod Outer Segments;Role;Sister Chromatid;Spatial Distribution;Structure;Surgeon;Tamoxifen;Testing;Vascular Endothelial Growth Factor Receptor;Vascular Endothelial Growth Factors;Vision Tests;Visual;college;in vivo;knockout gene;macrophage;mutant;neovascularization;null mutation;photoreceptor degeneration;prevent;public health medicine (field);receptor;research study;transcription factor


application_id: 7583041
project_number: 1R01NS061933-01A1
project_title: A specific microRNA (Mir-107) is a potential therapeutic target in Alzheimer's di
administering_ic: NINDS
award_notice_date: 2008-09-26
opportunity_number: PA-07-070
application_type: 1
activity_code: R01
ic: NS
serial_number: 061933
suffix: A1
program_official: REFOLO, LORENZO
project_start_date: 2008-09-30
project_end_date: 2012-02-28
study_section: Cellular and Molecular Biology of Neurodegeneration Study Section[CMND]
contact_pi_person_id: 1911366
contact_pi: NELSON, PETER T.
other_pis: Not Applicable
congressional_district: 06
department: OTHER HEALTH PROFESSIONS
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
project_terms:
3' Untranslated Regions;Affect;Alzheimer's Disease;Alzheimer's Disease Pathway;Alzheimer's disease model;Alzheimer's disease risk;Amyloid beta-Protein;Antibodies;Bezafibrate;Biochemical;Biological Assay;Brain;Cells;Clinical Trials;Co-Immunoprecipitations;Cultured Cells;Data;Dementia;Development;Down-Regulation;Glucose;Human;In Situ;In Situ Hybridization;In Vitro;Knock-in Mouse;Lipids;MK-886;Metabolic;Metabolic Pathway;Metabolism;MicroRNAs;Mus;Neurobiology;Neuroblastoma;Pathogenesis;Pathologic Processes;Pathology;Pathway interactions;Patients;Peptides;Pharmaceutical Preparations;Pharmacological Treatment;Play;Proteins;Publishing;RNA Messenger;Regulation;Research;Research Personnel;Role;Stimulus;Techniques;Testing;Time;Translations;abstracting;amyloidogenesis;base;beta-site APP cleaving enzyme 1;brain tissue;glucose metabolism;in vivo;mutant;neuropathology;neurotoxic;novel;polypeptide;programs;public health medicine (field);relating to nervous system;research study;therapeutic target;tissue culture


application_id: 7582346
project_number: 5R01HL080609-04
project_title: Oxidant Mediated Diaphragm Dysfunction in Diabetes
administering_ic: NHLBI
award_notice_date: 2009-03-13
application_type: 5
activity_code: R01
ic: HL
serial_number: 080609
program_official: CROXTON, THOMAS
project_start_date: 2006-04-01
project_end_date: 2012-03-31
study_section: Special Emphasis Panel[ZRG1-MOSS-E(02)]
contact_pi_person_id: 6210708
contact_pi: CALLAHAN, LEIGH A
other_pis: Not Applicable
congressional_district: 06
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-04-01
project_abstract:
Recent studies indicate that diabetes is associated with an increased incidence of respiratory failure aheightened risk of postoperative respiratory complications and a greater need for prolonged mechanicalventilation. However it is not known how diabetes produces these problems. One potential explanation isthat uncontrolled diabetes alters respiratory muscle function reducing the capacity of the respiratory pump.The purpose of the present proposal is to examine this issue. Our central hypothesis is that poorly controlleddiabetes induces severe free radical mediated diaphragm dysfunction. We will test this hypothesis in thefollowing groups of studies. Aim I studies will characterize the effects of uncontrolled diabetes on diaphragmspecific force generation changes in muscle mass and diaphragm endurance testing the hypothesisdiabetes induced alterations in diaphragm performance are related to increases in free radical generation.Aim II studies will interrogate a number of free radical generating pathways in muscle (including the cellsurface NADPH oxidase) and determine which pathways are responsible for increased free radicalgeneration in the diaphragm in diabetes. Aim III studies will determine if iNOS is upregulated in thediaphragm in diabetes and will test the hypothesis that iNOS acts as an upstream modulator of free radicalgeneration. Aim IV studies will examine several downstream targets of diabetes induced free radicalgeneration in the diaphragm that are responsible for reductions in diaphragm performance includingcontractile protein alterations calpain mediated reductions in muscle mass and alterations in mitochondrialATP generating capacity. A variety of physiologic biochemical proteomic fluorogenic pharmacologic andgenetic techniques will be used to test these hypotheses. Our preliminary data represent the firstdemonstration of upregulation of NADPH oxidase subunit proteins in skeletal muscle in any disease processand suggest that iNOS regulates NADPH oxidase activity and free radical generation in the diaphragm indiabetes. These new data should provide important information regarding the pathogenesis of diabetesinduced diaphragm dysfunction and uncover pathways which could provide novel therapeutic targets fortreatment of respiratory muscle weakness in this condition.

project_terms:
4-ethoxymethylene-2-phenyl-2-oxazoline-5-one;Ablation;Admission activity;Angiotensin II;Animal Model;Animals;Biochemical;Biological Assay;Calpain;Caring;Cell Culture Techniques;Cell surface;Cells;Cessation of life;Chemicals;Complement;Contractile Proteins;Coronary Arteriosclerosis;Coronary Artery Bypass;Critical Illness;Data;Databases;Development;Diabetes Mellitus;Diaphragm (Anatomy);Disease;Electron Transport;Endothelin-1;Environmental air flow;Fiber;Free Radical Scavengers;Free Radicals;Frequencies (time pattern);Functional disorder;Gel;Generations;Genetic Techniques;Glucose;Goals;Hand;Health;Hospitalization;Hospitals;Hyperglycemia;In Situ;In Vitro;Incidence;Injection of therapeutic agent;Interleukins;Ketones;Kidney Diseases;Knock-out;Link;Lipid Peroxidation;Measures;Mechanical ventilation;Mediating;Medical;Medicare;Membrane;Mitochondria;Morbidity - disease rate;Mortality Vital Statistics;Mus;Muscle;Muscle Fibers;Muscle Weakness;Muscle function;NADP;NADPH Oxidase;Neuropathy;Nitric Oxide Synthase;Operative Surgical Procedures;Oxidants;Oxygen Consumption;Pathogenesis;Pathway interactions;Patients;Performance;Phosphorylation;Physiological;Postoperative Period;Principal Investigator;Process;Production;Protein Subunits;Proteins;Proteomics;Pump;Rattus;Research;Research Design;Research Personnel;Respiratory Failure;Respiratory Muscles;Respiratory System;Respiratory Tract Infections;Respiratory physiology;Retinal Diseases;Review Literature;Risk;Role;Series;Signal Transduction;Skeletal muscle structure;Skin;Source;Streptozocin;Structure;Superoxide Dismutase;Superoxides;Techniques;Testing;Transgenic Animals;Transgenic Organisms;Up-Regulation (Physiology);Weaning;Western Blotting;Work;Workload;Xanthine Oxidase;calpastatin;chemical genetics;diabetes control;diabetic patient;high risk;hospital admission rate;human AKAP13 protein;improved;inhibitor/antagonist;mitochondrial dysfunction;muscle form;new therapeutic target;non-diabetic;overexpression;oxidation;prevent;programs;protein function;protein structure function;research study;respiratory;response;theories


application_id: 7581833
project_number: 1R01AA016013-01A2
project_title: Zinc inhibition of endotoxemia in alcoholic liver injury
administering_ic: NIAAA
award_notice_date: 2009-06-05
opportunity_number: PA-07-065
application_type: 1
activity_code: R01
ic: AA
serial_number: 016013
suffix: A2
program_official: RADAEVA, SVETLANA
project_start_date: 2009-06-05
project_end_date: 2011-05-31
study_section: Hepatobiliary Pathophysiology Study Section[HBPP]
contact_pi_person_id: 6870954
contact_pi: ZHOU, ZHANXIANG
other_pis: Not Applicable
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
project_abstract:
DESCRIPTION (provided by applicant): Zinc inhibition of endotoxemia in alcoholic liver injury Abstract Alcoholic liver disease (ALD) is an important health problem but an FDA-approved effective therapy is not available. A better understanding of the mechanisms involved in the pathogenesis of ALD will certainly pave the way to develop effective therapies for treating this disease. Several hypotheses regarding the mechanisms by which alcohol induces liver injury have been postulated including ethanol metabolism-generated oxidative stress endotoxemia and proinflammatory cytokine production. Each of the three factors has been shown to contribute significantly to ALD. However the critical trigger for these detrimental events has not been defined. Although previous studies have largely focused on the direct effects of ethanol on the liver clinical evidence indicates that excessive ethanol consumption is necessary but not sufficient to induce liver injury. Gut-derived endotoxin has been suggested as one of the most important cofactors in development of ALD. Endotoxin is known to trigger proinflammatory cytokine production in the liver leading to inflammation oxidative stress and eventually cell death. While endotoxemia is well documented in patients with ALD the mechanisms involved in the development of endotoxemia have not been fully understood. Given the fact that only alcoholics with gut leakiness develop ALD intestinal barrier dysfunction is likely the cause of endotoxemia. Therefore suppression of endotoxemia by sealing the leaky gut could be very an attractive approach for treating ALD. Our previous studies have shown that inhibition of endotoxemia is associated with zinc prevention of acute ethanol-induced liver injury. Importantly our preliminary data identify a novel potential mechanism by which ethanol and zinc regulate the intestinal barrier. We found that zinc deficiency and dysfunction of zinc finger transcription factors disrupt the barrier function of Caco-2 cells through depressing junction proteins. In this context we hypothesize that zinc homeostasis plays a critical role in regulation of intestinal barrier function. We will carry out the following specific aims and research approaches in this project. Aim 1 will determine the role of zinc deficiency in the pathogenesis of ethanol-induced intestinal barrier dysfunction and endotoxemia. A chronic ethanol exposure rat model will be utilized to induce alcoholic endotoxemia. First we will determine disturbance of intestinal zinc homeostasis in association with ethanol-induced intestinal barrier dysfunction and endotoxemia. Second the impact of zinc deficiency on intestinal barrier function and the possible synergistic action with ethanol will be determined by using a dietary zinc deficiency model. We expect the results of Aim 1 to demonstrate that zinc deprivation is a causal factor in the pathogenesis of ethanol-induced intestinal barrier disruption. Aim 2 will investigate the molecular mechanisms by which zinc deficiency interferes with intestinal barrier function. Caco-2 cell culture model will be utilized to determine whether ethanol-induced zinc deficiency lead to dysfunction of zinc finger transcription factors and whether zinc finger transcription factors critically regulate epithelial barrier structure and function. We will first define the links between ethanol-induced ROS generation and zinc mobilization and depression of zinc finger transcription factors. We will then define the role of zinc finger transcription factors in regulation of tight junction proteins and barrier function by gene silencing and expression. We expect Aim 2 to demonstrate that zinc mobilization from zinc finger transcription factors is a critical molecular event in ethanol-induced epithelial barrier disruption. Aim 3 will evaluate the beneficial effect of dietary zinc supplementation on ethanol-induced gut leakiness and endotoxemia. A chronic ethanol exposure rat model will be utilized to evaluate the beneficial effects of dietary zinc supplementation on ethanol-induced intestinal leakiness and the consequent endotoxemia and hepatitis. We expect that dietary zinc supplementation through preserving zinc finger transcription factors will seal the leaky gut and attenuate endotoxemia and the consequent hepatitis. These studies will provide novel insights into the role of zinc in modulation of ethanol-induced gut leakiness and the consequent endotoxemia and hepatitis. The results would have high potential leading to a simplistic approach to prevention/treatment of ALD. PUBLIC HEALTH RELEVANCE: Alcoholic liver disease is a common health problem. Although much progress has been made in understanding the pathogenesis of Alcoholic liver disease effective therapies are lacking. Although previous studies have largely focused on the direct effects of ethanol on the liver clinical evidence indicates that excessive ethanol consumption is necessary but not sufficient to induce liver injury. Gut-derived endotoxin has been suggested as one of the most important cofactors in development of alcoholic liver disease. Endotoxin is known to trigger proinflammatory cytokine production in the liver leading to inflammation oxidative stress and eventually cell death. While endotoxemia is well documented in patients with alcoholic liver disease the mechanisms involved in the development of endotoxemia have not been fully understood. Given the fact that only alcoholics with gut leakiness develop alcoholic liver disease intestinal barrier dysfunction is likely the cause of endotoxemia. Therefore suppression of endotoxemia by sealing the leaky gut could be very an attractive approach for treating AL alcoholic liver disease.

project_terms:
Acute;Alcohol consumption;Alcoholic Liver Diseases;Attenuated;Caco-2 Cells;Cell Culture Techniques;Cell Death;Chronic;Clinical;Data;Development;Dietary Zinc;Disease;Endotoxemia;Endotoxins;Epithelial;Ethanol;Ethanol Metabolism;Event;FDA approved;Functional disorder;Gene Silencing;Generations;Health;Hepatitis;Homeostasis;Inflammation;Injury;Intestines;Lead;Link;Liver;Modeling;Molecular;Oxidative Stress;Pathogenesis;Patients;Play;Prevention;Prevention approach;Principal Investigator;Production;Proteins;Rattus;Regulation;Research;Role;Structure;Supplementation;Tight Junctions;Zinc;Zinc Fingers;Zinc deficiency;abstracting;alcohol effect;alcohol exposure;cofactor;cytokine;depressed;depression;deprivation;effective therapy;insight;novel;problem drinker;programs;public health relevance;seal;transcription factor

public_health_relevance:
Principal Investigator/Program Director (Last First Middle): Zhou ZhanxiangProject Narrative Alcoholic liver disease is a common health problem. Although much progress has been madein understanding the pathogenesis of Alcoholic liver disease effective therapies are lacking.Although previous studies have largely focused on the direct effects of ethanol on the liver clinicalevidence indicates that excessive ethanol consumption is necessary but not sufficient to induce liverinjury. Gut-derived endotoxin has been suggested as one of the most important cofactors indevelopment of alcoholic liver disease. Endotoxin is known to trigger proinflammatory cytokineproduction in the liver leading to inflammation oxidative stress and eventually cell death. Whileendotoxemia is well documented in patients with alcoholic liver disease the mechanisms involved inthe development of endotoxemia have not been fully understood. Given the fact that only alcoholicswith gut leakiness develop alcoholic liver disease intestinal barrier dysfunction is likely the cause ofendotoxemia. Therefore suppression of endotoxemia by sealing the leaky gut could be very anattractive approach for treating AL alcoholic liver disease.PHS 398/2590 (Rev. 09/04 Reissued 4/2006) Page Continuation Format Page


application_id: 7581293
project_number: 3R01DC002736-10S1
project_title: Functional Domains and Expression of Olfactory Receptors
administering_ic: NIDCD
award_notice_date: 2008-03-07
application_type: 3
activity_code: R01
ic: DC
serial_number: 002736
suffix: S1
program_official: DAVIS, BARRY
project_start_date: 1995-08-01
project_end_date: 2011-06-30
study_section: Special Emphasis Panel[ZRG1-IFCN-K(03)M]
contact_pi_person_id: 1883753
contact_pi: MCCLINTOCK, TIMOTHY S
other_pis: Not Applicable
congressional_district: 06
department: PHYSIOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
The mammalian olfactory epithelium does two remarkablethings with its olfactory sensory neurons. Theseneurons detect odorants translating the structure of volatile chemicals into a neural information code andthe epithelium can replace these neurons even if they are completely eliminated. These properties are ofsignificant interest for both basic and applied neuroscience research. The goal of this project is to generatea finely detailed description of the phenotypes of the mature olfactory sensory neurons and their immediateprogenitor cells then use this description to predict critical steps in the molecular mechanisms that lead tothe genesis of these neurons their ability to detect certain odors and their ability to survive in their exposedposition. The first aim of this project combines a system-wide view of gene expression with our ability topurify certain cell types so that we can assign gene expression patterns and the biological processes theyrepresent to their correct homes in the cells of the epithelium. The second aim takes advantage ofpredictions about genes whose products regulate the activity of other genes made by our preliminary data.We will test whether targeted knockout of six of these regulator genes all expressed by immature olfactorysensory neurons causes deficits in either the production of mature neurons or in critical functions of theseneurons. The third aim is based on our belief that within the expression patterns we observe in olfactorysensory neurons are sets of genes responsible for survival of the neurons. We will use odor stimulationwhich is known to enhance survival to increase the activity of pro-survival genes (or suppress anti-survivalgenes) so that they can be detected. This project is an integrated approach to understanding the geneswhose activity is important for generating the phenotype of mature olfactory sensory neurons and thenmaintaining these cells in the face of significant challenges.

project_terms:
ASCL1 protein human;Abbreviations;Age;Analysis of Variance;B-Lymphocytes;Belief;Biological Process;Boxing;Bromodeoxyuridine;Cell Adhesion;Cells;Chemicals;Chronic Lymphocytic Leukemia;Cilia;Code;Condition;Data;Defect;Energy Metabolism;Environment;Epithelium;Epithelium Olfactory;Event;Face;Flagella;Fluorescence-Activated Cell Sorting;Galactosidase;Gel;Gene Expression;Gene Silencing;Gene Targeting;Genes;Genes LacZ;Genes Regulator;Germ Cells;Goals;Green Fluorescent Proteins;Growth Associated Protein 43;Home environment;Homeobox;Individual;Ion Transport;Knock-out;Lead;Link;Lymphoid;Lymphoma;Maintenance;Measures;Molecular;Mus;Myelogenous;Neuro-Oncological Ventral Antigen 2;Neurons;Neurons Afferent;Neurosciences Research;Odors;Pattern;Phenotype;Polymerase Chain Reaction;Population;Positioning Attribute;Production;Property;RNA;RNA Messenger;Rate;Regulation;Research Personnel;Reverse Transcription;Signal Transduction;Sorting - Cell Movement;Spermatogenesis;Stem cells;Structure;Synaptic Transmission;System;Testing;Tissues;Transcription Genetic;Translating;base;cell injury;cell type;chromatin remodeling;cilium biogenesis;day;deprivation;enhanced green fluorescent protein;experience;interest;knockout gene;leukemia;leukemia/lymphoma;neurogenesis;olfactory marker protein;olfactory receptor;postnatal;precursor cell;progenitor;programs;relating to nervous system;tool;transcription factor


application_id: 7580952
project_number: 5R44DK070374-04
project_title: A Test for Salt Sensitivity in People with Essential Hypertension
administering_ic: NIDDK
award_notice_date: 2009-02-27
opportunity_number: PA-07-280
application_type: 5
activity_code: R44
ic: DK
serial_number: 070374
program_official: GOSSETT, DANIEL ROBERT
project_start_date: 2005-04-01
project_end_date: 2010-08-31
study_section: Cellular and Molecular Biology of the Kidney Study Section[CMBK]
contact_pi_person_id: 1897474
contact_pi: CARRITHERS, STEPHEN L
other_pis: Not Applicable
congressional_district: 04
department: Unavailable
primary_duns: 189577070
primary_uei: DJ6WUEKKFBM8
duns_number: 189577070
uei: DJ6WUEKKFBM8
fips: US
organization_id: 10001287
organization_name: SEQUELA
organization_city: PEWEE VALLEY
organization_state: KY
organization_type: Domestic For-Profits
organization_zip: 400569116
organization_country: UNITED STATES
arra_indicator: N
project_abstract:
DESCRIPTION (provided by applicant):   
  
Project Summary:  In Phase I we developed a model system and a prototype Salt Sensitivity Assay to establish  proof-of-principle . In Phase II we propose the evaluation of the prototype that will quantitatively measure our biomarker in the target population. An ideal biomarker for salt sensitivity would be one that is linked to the underlying cause of salt sensitivity and not disease symptoms. It is our hypothesis that this biomarker can be accurately measured using a monoclonal antibody-based direct quantitative ELISA. The assay will allow physicians to identify salt sensitivity in newly diagnosed hypertensive patients so that appropriate therapy can begin as early as possible. The information gained from this accurate screening test will lead to basic research investigations of the biological mechanisms underlying salt sensitivity and its pathophysiological consequences such as hypertension CHF renal disease and edema. We request Phase II support so that we can evaluate our prototype Salt Sensitivity Assay in a pivotal study with the ultimate goal of obtaining FDA approval. In addition our proposal also addresses several research questions and explores an exciting new secondary application of our assay in the assessment of renal function.  
  
Project Narrative   
Hypertension affects almost 50 million people in the United States which places them at higher risk for chronic renal failure and cardiovascular disease. Of those affected about half are salt-sensitive. We will develop an ELISA for hypertensive people that can be used to distinguish between salt sensitive and salt resistant individuals.

project_terms:
Acute;Address;Adult;Affect;Affinity;Animal Model;Animals;Archives;Award;Basic Science;Biochemical;Biological;Biological Assay;Biological Models;Blood;Blood Pressure;Bolus Infusion;Cardiovascular Diseases;Chronic Kidney Failure;Clinical Research;Clinical Trials;Collaborations;Development;Diagnostic;Disease;Edema;End stage renal failure;Endocrine;Endocrinology;Enteral;Enzyme-Linked Immunosorbent Assay;Essential Hypertension;Evaluation;Excretory function;Funding;Goals;Hematological Disease;Homeostasis;Hour;Human;Hypertension;Individual;Infusion procedures;Intake;Intestines;Investigation;Kidney;Kidney Diseases;Knockout Mice;Laboratories;Lead;Letters;Link;Maine;Marketing;Measures;Messenger RNA;Monoclonal Antibodies;Mus;NIH Program Announcements;National Heart Lung and Blood Institute;National Institute of Diabetes and Digestive and Kidney Diseases;Natriuretic Peptides;Newly Diagnosed;Oral;Participant;Patients;Peptides;Phase;Physicians;Physiological;Plasma;Play;Preparation;Principal Investigator;Protocols documentation;Radioimmunoassay;Rattus;Reagent;Regulation;Renal function;Reporting;Request for Applications;Research;Research Ethics Committees;Research Personnel;Resistance;Rodent Model;Role;Sampling;Screening procedure;Series;Small Business Innovation Research Grant;Sodium;Sodium Chloride;Sodium-Restricted Diet;Staging;Stomach;Symptoms;Target Populations;Testing;United States;United States National Institutes of Health;Urine;Work;base;biobank;biomarker;guanylin;high risk;medical schools;meetings;mouse model;normotensive;polyclonal antibody;programs;prohormone;prototype;research study;response;salt intake;salt sensitive;scale up;uroguanylin;urologic;validation studies


application_id: 7579932
project_number: 5R01DA021155-04
project_title: Agonist Replacement Therapy for Cocaine Dependence: Identifying Novel Medications
administering_ic: NIDA
award_notice_date: 2009-03-24
application_type: 5
activity_code: R01
ic: DA
serial_number: 021155
program_official: BOUGH, KRISTOPHER J
project_start_date: 2006-06-01
project_end_date: 2011-09-30
study_section: HIV and Substance Use Research Study Section [NIDA-E]
contact_pi_person_id: 1888410
contact_pi: RUSH, CRAIG R
other_pis: Not Applicable
congressional_district: 06
department: PSYCHOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-04-01
project_abstract:
Cocaine abuse and dependence continue to be significant public health concerns. The number ofAmericans that used cocaine in the past month the percentage of 12th- 10th- and 8th-graders that usedcocaine in the past year and the percentage of treatment admissions involving cocaine has remained stablein recent years. In 1996 cocaine use cost society over $45 billion due to medical consequences lostproductivity and crime. Because of the public-health concerns and costs associated with its abuseidentifying a pharmacotherapy for cocaine dependence is a priority with the National Institute on Drug Abuse(N.I.D.A.). A pharmacological adjunct for cocaine dependence has not yet been identified. The results of clinical trials suggest that agonist replacement therapies (e.g. d-amphetamine) may beeffective for cocaine dependence. Because cf-amphetamine reduces cocaine use these clinical findings canbe used as a reference to identify human laboratory procedures for screening putative pharmacotherapies.Identifying procedures for assessing the efficacy ofputative pharmacotherapies is important because humanlaboratory studies can be conducted more rapidly/and/efficiently than clinical trials. The present project has two specific aims. The first specific aim is to demonstrate the sensitivity andpredictive validity of human laboratory procedures commonly used to screen putativepharmacotherapies for cocaine dependence. To accomplish this aim we will conduct two "proof-of-concept" studies. We will first demonstrate the safety and tolerability of d-amphetamine-cocainecombinations (Exp. 1). We will then 'demonstrate that d-amphetamine maintenance attenuates thereinforcing effects of cocaine (Exp. 2). The ability to attenuate the reinforcing effects of cocaine may be animportant characteristic of an effective pharmacotherapy. The results of these studies will help elucidate theoptimal conditions (e.g. dose) under which d-amphetamine might be expected to be effective. The second specific aim is to determine the efficacy of atomoxetine (Strattera) as a putativeagonist replacement pharmacotherapy for cocaine dependence. To accomplish this aim we will conducttwo experiments to determine the effects of cocaine during atomoxetine maintenance. We will firstdemonstrate the safety and tolerability of atomoxetine-cocaine combinations (Exp. 3). Finally we willdetermine the reinforcing effects of intranasal cocaine during atomoxetine maintenance (Exp. 4).Atomoxetine a potent norepinephrine uptake blocker was chosen for study because its pharmacologicaland behavioral effects overlap to some extent with those of d-amphetamine but it appears to have lessabuse potential. Identifying novel agonist replacement therapies is important because clinicians may bereluctant to use d-amphetamine because of its abuse potential.

project_terms:
Accident and Emergency department;Admission activity;Agonist;American;Amphetamines;Attenuated;Behavior;Behavioral;Characteristics;Chronic;Clinical;Clinical Trials;Cocaine;Cocaine Abuse;Cocaine Dependences;Crime;Dependence;Dextroamphetamine;Dose;Event;Human;Individual;Institution;Kentucky;Knowledge;Laboratories;Laboratory Procedures;Laboratory Study;Location;Maintenance;Measures;Medical;National Institute of Drug Abuse;Nicotine;Norepinephrine;Opiate Addiction;Pharmaceutical Preparations;Pharmacotherapy;Pilot Projects;Procedures;Productivity;Psychostimulant dependence;Publishing;Questionnaires;Recording of previous events;Replacement Therapy;Reporting;Research;Research Design;Research Personnel;Safety;Schedule;Self Administration;Societies;atomoxetine;cocaine use;cost;drug reinforcement;novel;preclinical study;programs;public health medicine (field);research study;stimulant abuse;uptake;volunteer


application_id: 7579382
project_number: 2R01DK053220-10A2
project_title: DNA sequences impact estrogen and antiestrogen activity
administering_ic: NIDDK
award_notice_date: 2008-09-22
opportunity_number: PA-07-070
application_type: 2
activity_code: R01
ic: DK
serial_number: 053220
suffix: A2
program_official: MARGOLIS, RONALD N
project_start_date: 1998-04-01
project_end_date: 2012-07-31
study_section: Integrative and Clinical Endocrinology and Reproduction Study Section[ICER]
contact_pi_person_id: 1888054
contact_pi: KLINGE, CAROLYN M.
other_pis: Not Applicable
congressional_district: 03
department: BIOCHEMISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
project_terms:
4-Hydroxy-Tamoxifen;Acetylation;Acute;Address;Age;Aorta;Apoptosis;Apoptotic;Area;Binding Sites;Biogenesis;Biological;Biological Assay;Breast;Breast Cancer Cell;Calorimetry;Cell Cycle;Cell Cycle Proteins;Cell Nucleus;Cell Proliferation;Cells;Communication;Consumption;Cyclin D1;Cytochrome c Reductase;DNA Maintenance;DNA Polymerase II;DNA Sequence;DNA Mitochondrial;Estradiol;Estrogen Antagonists;Estrogen Receptor Modulators;Estrogen Receptors;Estrogens;Event;Fluorescence;Gene Expression;Gene Proteins;Gene Targeting;Generations;Genes;Genome;Goals;Heart;Heart Arrest;Heating;Histones;Human;Hypothalamic structure;Immunohistochemistry;Investigation;Kidney;Lead;Ligands;Liver;Lung;MCF7 cell;Malignant Neoplasms;Malignant neoplasm of lung;Mammary Gland Parenchyma;Mammary Neoplasms;Mammary gland;Measures;Mediating;Mice Knockout;Mitochondria;Molecular;Mus;Nerve Degeneration;Nuclear;Numbers;Outcome;Output;Pathway interactions;Play;Prevention;Production;Promoter Regions (Genetics);Promotor (Genetics);Proteins;RNA;RNA Messenger;RNA Small Interfering;Reactive Oxygen Species;Recruitment Activity;Regulation;Reporting;Research;Respiratory Chain;Response Elements;Role;Selective Estrogen Receptor Modulators;Specimen;Steroids;Tamoxifen;Testing;Time;Tissues;Titrations;Transcription Genetic;Trauma;Tumor Tissue;Uterus;cancer cell;chromatin immunoprecipitation;cytochrome c oxidase;in vivo;insight;mitochondrial dysfunction;neoplastic;neoplastic cell;novel;nuclear respiratory factor;ovex (pesticide);protein expression;public health medicine (field);research study;respiratory;response;stroke;survivin;transcription factor;tumor progression;tumor xenograft


application_id: 7578890
project_number: 5R01CA104333-05
project_title: DNA Mismatch Repair Deficiency and Leukemia Relapse
administering_ic: NCI
award_notice_date: 2009-01-26
application_type: 5
activity_code: R01
ic: CA
serial_number: 104333
program_official: OKANO, PAUL
project_start_date: 2005-04-01
project_end_date: 2012-02-28
study_section: Cancer Genetics Study Section[CG]
contact_pi_person_id: 7956619
contact_pi: GU, LIYA
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-03-01
project_abstract:
DESCRIPTION (provided by applicant): The long-term goal of this project is to understand the molecular mechanisms underlying leukemia relapse. There are more than 21000 deaths to relapsed leukemia each year in the United States but the molecular basis of this deadly disease is still unknown. Since leukemia relapse is always associated with chemotherapy and since cells exposed to therapeutic agents usually acquire a mismatch repair (MMR) deficient phenotype we hypothesize that leukemia relapse in many cases is caused by a small fraction of leukemic cells that have adopted an MMR deficient phenotype during the course of chemotherapy. Our preliminary studies have showed that defects in MMR are indeed associated with cell lines derived from relapsed leukemia and patients with relapsed leukemia. To further test our hypothesis this application proposes both genetic and biochemical approaches to analyze the relationship between relapsed leukemia and MMR proficiency. First real-time PCR will be used to analyze the status of microsatellite sequences in adult acute leukemia patient samples at presentation remission and relapse to dynamically and quantitatively determine how leukemic cells transform from a microsatellite stable form to a microsatellite instable form during the development of relapse. Second leukemic cells from relapsed patients will be analyzed for genetic alterations and epigenetic modifications in key MMR genes such as hMSH2 and hMLH1 using combination technologies of PCR-based single strand conformation polymorphism DNA sequencing and methylation-specific PCR. Third individual alterations identified in leukemia patients will be introduced into MMR genes to express recombinant mutant proteins. To determine the actual impact of these alterations on MMR function individual recombinant mutant proteins will be examined for their ability to restore MMR to the corresponding MMR mutant extracts using an in vitro functional MMR assay. This study will provide significant insight into the mechanism underlying leukemia relapse as well as vital information for designing therapeutic regimens for the disease.

project_terms:
Acute leukemia;Adopted;Adult;Biochemical;Biological Assay;Cell Line;Cells;Cessation of life;Characteristics;Complement;DNA;DNA Sequence;Data;Defect;Detection;Detection of Minimal Residual Disease;Development;Diagnostic;Disease;Disease remission;Epigenetic Process;Evolution;Genes;Genetic;Goals;In Vitro;In complete remission;Individual;Leukemia Myelocytic Acute;Leukemic Cell;MLH1 gene;Methylation;Microsatellite Instability;Microsatellite Repeats;Mismatch Repair;Modification;Molecular;Mutation;Nuclear Extract;Pathogenesis;Patients;Phenotype;Proteins;Publishing;Recombinants;Relapse;Research;Research Personnel;Residual state;Sampling;Single-Stranded Conformational Polymorphism;Site-Directed Mutagenesis;Staging;Technology;Testing;Therapeutic;Therapeutic Agents;Time;Treatment Protocols;United States;Work;base;chemotherapy;design;expectation;expression vector;insight;leukemia;mutant;prevent;programs;tool


application_id: 7578836
project_number: 5R01CA049797-18
project_title: Mechanism of MnSOD expression in normal and tumor cells
administering_ic: NCI
award_notice_date: 2009-02-09
application_type: 5
activity_code: R01
ic: CA
serial_number: 049797
program_official: MIETZ, JUDY
project_start_date: 1989-12-01
project_end_date: 2010-08-28
study_section: Cancer Etiology Study Section[CE]
contact_pi_person_id: 3147341
contact_pi: ST CLAIR, DARET K
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-03-01
project_abstract:
DESCRIPTION (provided by applicant): The overall goal of this research is to determine the molecular mechanisms that control the expression of the human MnSOD gene during tumor promotion. It is well documented that MnSOD level is altered in transformed cells. Our previous studies demonstrate that overexpression of the MnSOD gene suppresses tumorigenesis in a multistage skin cancer model. However when and how MnSOD expression is modulated during carcinogenesis is unknown. We have generated several lines of transgenic mice expressing a luciferase reporter gene under the control of MnSOD promoter/enhancer elements. This unique animal model provides an outstanding opportunity for investigating changes in MnSOD expression during the carcinogenesis process in animals by a non-invasive method. We hypothesize that repetitive exposure to tumor promoter leads to inactivation of MnSOD expression. Specific Aim 1 will determine at what point the expression of MnSOD is reduced during the process of cancer development using transgenic mice harboring a MnSOD promoter-driven luciferase reporter and bioluminescence-imaging strategies to noninvasively and quantitatively image MnSOD expression in living mice. Specific Aim 2 will investigate how changes in MnSOD expression occur in vivo using chromatin immunoprecipitation (ChIP) assays DNA sequencing and proteomic analyses. Specific Aim 3 will identify transcription factors and co-activators/repressors necessary for transcriptional modulation of the MnSOD gene using DNA binding siRNA and protein/protein interaction methods. The results of the proposed studies will provide information on when and how the expression of MnSOD is altered during tumorigenesis. Because of the essential role of MnSOD for the survival of aerobic life and its well documented role in the prevention of oxidative stress-mediated tissue injury and cancer formation understanding how the expression of MnSOD can be regulated during cancer development is likely to have broad implications for the prevention of cancer.

project_terms:
910-Dimethyl-12-benzanthracene;Acetates;Address;Aerobic;Animal Model;Animals;Anthracenes;Antioxidants;Biochemical;Biological;Biological Assay;Bioluminescence;Cancer Control;Cancer Model;Cells;Complex;Coupled;DNA;DNA Binding;DNA Sequence;DNA Structure;DNA-Binding Proteins;Development;Discipline;Enhancer Elements (Genetics);Enhancers;Enzymes;Epithelial;Exposure to;Family;Future;Gene Expression;Gene Silencing;Genes;Genetic Transcription;Goals;Human;Image;Image Analysis;Incidence;Injury;Lead;Life;Luciferases;Malignant Neoplasms;Manganese;Measures;Mediating;Methods;Mitochondria;Modeling;Molecular;Molecular Biology;Monitor;Mus;Ontology;Oxidative Stress;Papilloma;Phase;Prevention;Process;Promotor (Genetics);Proteins;Proteomics;Protocols documentation;Regulation;Reporter;Reporter Genes;Research;Research Personnel;Reverse Transcription;Role;Site-Directed Mutagenesis;Skin;Skin Cancer;Skin Carcinogenesis;Skin Tissue;Small Interfering RNA;Staging;Superoxide Dismutase;Testing;Time;Tissues;Transgenic Mice;Tumor Promoters;Tumor Promotion;Tumor Suppressor Genes;base;cancer prevention;carcinogenesis;cell transformation;chromatin immunoprecipitation;design;in vivo;insight;member;neoplastic cell;novel;overexpression;prevent;protein protein interaction;tool;transcription factor;tumor;tumorigenesis


application_id: 7578781
project_number: 4R44HD055019-02
project_title: Adaptive High Intensity Electrical Stimulation for Post-Surgical Rehabilitation
administering_ic: NICHD
award_notice_date: 2008-04-14
opportunity_number: PA-06-120
application_type: 4
activity_code: R44
ic: HD
serial_number: 055019
program_official: SHINOWARA, NANCY
project_start_date: 2008-04-15
project_end_date: 2010-03-31
study_section: Special Emphasis Panel[ZRG1-MOSS-L(10)B]
contact_pi_person_id: 7771781
contact_pi: HARTMAN, ERIC C
other_pis: Not Applicable
congressional_district: 06
department: Unavailable
primary_duns: 129360637
duns_number: 129360637
fips: US
organization_id: 4168101
organization_name: CUSTOMKYNETICS, INC.
organization_city: NICHOLASVILLE
organization_state: KY
organization_type: Domestic For-Profits
organization_zip: 403401290
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2008-04-15
budget_end_date: 2009-03-31
project_abstract:
DESCRIPTION (provided by applicant): Recovery of quadriceps muscle force following post-surgical knee immobilization is a significant therapeutic aim which is associated with quality of gait and the ability to perform activities of daily living. Several studies from various research groups have shown that neuromuscular electrical stimulation (NMES) used in conjunction with a comprehensive post-surgical rehabilitation program is a safe and highly effective method for achieving quadriceps strengthening. The most profound results have been demonstrated with use of high intensity NMES technique in which a few very strong isometric contractions of the quadriceps muscle were performed several times per week during a physical therapy session in which the patient was seated on a biomechanical dynamometer. Efficacy of this technique has been demonstrated for individuals undergoing rehabilitation following surgical reconstruction of the anterior cruciate ligament (ACLR); however widespread clinical acceptance of the technique has been limited. We assert that this high intensity electrical stimulation technique would be more widely practiced: 1) if a low cost practical cohesive system were available to replace costly and loosely connected research-based apparatus and 2) if the system involved an NMES unit that controlled stimulation automatically using an outcome-based paradigm that did not require incessant involvement of the therapist. We propose a novel rehabilitation system indicated for quadriceps strengthening during post-surgical knee immobilization in which the knee joint will be stabilized using an instrumented post-surgical knee brace and stimulation is delivered by a high output portable NMES unit with autonomous adaptive stimulation control capabilities. The target markets for this device would be clinics who serve patients undergoing rehabilitation following ACLR or total knee arthroplasty (TKA). The target price for the system will be $4000. The goals of this FastTrack SBIR project are therefore to demonstrate feasibility of the adaptive stimulation control approach in Phase I using laboratory-based apparatus. We will interface our adaptive stimulator to the KinCom dynamometer and show that the stimulator can elicit a contraction of sufficient strength that function outcomes could be expected and demonstrate that the adaptive controller can develop appropriate stimulation patterns for use in this low-cycle count application. The Phase II goals will be: 1) to develop an instrumented knee brace capable of stabilizing the knee during near maximal isometric contractions and obtaining measurements of the resulting torque; 2) to implement a rapid training version of our adaptive stimulation controller that is suited for use in this low cycle count application; 3) to implement an alternate fundamental stimulation waveform that may be more comfortable to some users; and 4) to demonstrate efficacy of the proposed system for quadriceps strengthening following ACLR or TKA. / Relevance The proposed work may benefit public health through development of an electrical stimulation exercise device indicated for quadriceps strengthening during post-surgical immobilization following surgical repair of the anterior cruciate ligament (ACLR) or total knee arthroplasty (TKA). Quadriceps strengthening has been shown to improve gait and improve performance of activities of daily living (ADLs). There are approximately 100000 ACLR and 400000 TKA surgeries per year in the United States.

project_terms:
Activities of Daily Living;Algorithms;Animal Welfare;Anterior Cruciate Ligament;Appendix;Arthroplasty Replacement Knee;Bibliography;Biomechanics;Braces-Orthopedic appliances;Clinic;Clinical;Count;Country;Degenerative polyarthritis;Delaware;Devices;Electric Stimulation;Environment;Equipment;Ethics Committees Research;Exercise;Gait;Goals;Government;IACUC;Immobilization;Impact Environmental;Individual;International;Isometric Contraction;Isometric Exercise;Knee;Knee joint;Laboratories;Lead;Marketing;Measurement;Methods;Muscle;Names;Numbers;Operative Surgical Procedures;Other Resources;Outcome;Output;Patients;Pattern;Phase;Physical therapy;Pilot Projects;Price;Principal Investigator;Protocols documentation;Recovery;Recruitment Activity;Rehabilitation therapy;Research;Signal Transduction;Small Business Funding Mechanisms;Small Business Innovation Research Grant;System;Techniques;Therapeutic;Time;Torque;Training;Transducers;Universities;Vertebrates;Week;Work;abstracting;analog;base;cost;desire;expiration;human subject;instrument;novel;programs;prototype;reconstruction


application_id: 7578719
project_number: 2R01DE014605-07A1
project_title: Intra- and interspecies communication in oral bacteria
administering_ic: NIDCR
award_notice_date: 2008-09-26
opportunity_number: PA-07-070
application_type: 2
activity_code: R01
ic: DE
serial_number: 014605
suffix: A1
program_official: LUNSFORD, DWAYNE
project_start_date: 2003-02-01
project_end_date: 2013-07-31
study_section: Special Emphasis Panel[ZRG1 MOSS-E (02)]
contact_pi_person_id: 1859425
contact_pi: DEMUTH, DONALD R
other_pis: Not Applicable
congressional_district: 03
department: DENTISTRY
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF DENTISTRY/ORAL HYGN
organization_zip: 402920001
organization_country: UNITED STATES
project_terms:
Actinobacillus actinomycetemcomitans;Address;Adult;Affinity;Aldehyde-Lyases;Bacteria;Cell Communication;Cell physiology;Cells;Communication;Communities;Complex;DNA Binding;Data;Density Cell;Dental Plaque;Dependency (Psychology);Detection;Development;Dose;Environment;Enzymes;Escherichia coli;Event;Expenditure;Feedback;Fructosediphosphate Aldolase;Funding;Gene Expression;Gene Mutation;Genes;Genes Regulator;Gingival Pocket;Goals;Growth;Growth and Development function;Heart Diseases;Helix-Turn-Helix Motifs;Hemin;Hybrids;Individual;Iron;Kinetics;Lead;Life;Link;Mediating;Microbial Biofilms;Modeling;Molecular;Monitor;Mouth Diseases;Nutrient;Operon;Oral;Oral cavity;Organism;Outcome;Pathway interactions;Periodontal Diseases;Periodontitis;Pharmaceutical Preparations;Phosphotransferases;Population;Porphyromonas gingivalis;Prevention;Process;Promoter Regions (Genetics);Promotor (Genetics);Proteins;Range;Reporting;Salmonella;Sampling;Series;Signal Transduction;Site;Solutions;System;Testing;Therapeutic Intervention;Transport Process;United States;VAI-2;Vibrio;Virulence;Virulence Factors;design;microbial;microbial community;mutant;novel therapeutics;oral bacteria;oral biofilm;oral pathogen;pathogen;prevent;public health medicine (field);quorum sensing;receptor;response;sensor;uptake


application_id: 7577511
project_number: 5F31NS059274-02
project_title: Specific targeting of a neuronal subset using a novel chimeric vector pseudotype
administering_ic: NINDS
award_notice_date: 2008-12-15
application_type: 5
activity_code: F31
ic: NS
serial_number: 059274
program_official: KLEITMAN, NAOMI
project_start_date: 2008-01-01
project_end_date: 2009-12-31
study_section: Special Emphasis Panel[ZRG1-F01-P(20)L]
contact_pi_person_id: 8715331
contact_pi: TRIMBY, CHRISTOPHER
other_pis: Not Applicable
congressional_district: 06
department: PHYSIOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-01-01
project_abstract:
DESCRIPTION (provided by applicant): This proposal will investigate the hypothesis that the rabies virus envelope glycoprotein (RvG) can be used as a base for making a novel chimeric envelope glycoprotein to be called RvGN2 by inserting Loop 2 from Nerve Growth Factor (NGF) in place of the "toxin-like" loop of RvG. Loop 2 confers the ability of NGF to bind the TrkA receptor which is a receptor that is primarily expressed on sensory neurons including those projecting from the dorsal root into lamina I & II of the spinal cord. The RvGN2 chimera will still maintain the ability to be retrogradely transported making the vector more attractive for clinical applications by allowing the potential for a less invasive delivery strategy. The more specific aims of this project will be to test the hypothesis that the RvG can act as a functionally viable basis for engineered retargeting. This will be assessed by immunocytochemistry to detect RvGN2 expression on the surface of transfected cells. The next step will be to test the hypothesis that RvGN2 reporter viruses will preferentially infect cells in vitro that express TrkA over cells that are permissive to wild- type Rabies virus infection. Transient transfection of the TrkA receptor will also be used to "rescue" resistant cell lines. The last aim will test the hypothesis that the in vitro targeting profile will be maintained when RvGN2 reporter virus is administered to rats in vivo by injection into the spinal cord. The second part of this aim is to show that peripheral delivery by intramuscular or intradermal injection will preserve this targeting profile. Immunohistochemistry will then be used on tissue sections with antibodies to detect different markers indicative of separate subsets of neurons. This staining pattern will be compared to the transduction pattern of the reporter viruses to assess which neuronal subpopulations were transduced. At this time viral gene therapy vectors cannot differentiate among subsets of neurons making them impractical to treat many disorders. The capability to selectively target subsets of neurons will allow the basis for treatment of a multitude of disorders from chronic pain to aiding in spinal cord regeneration. And the ability to be retrogradely transported will allow for less invasive delivery of these vectors as opposed to direct injections into the spinal cord.

project_terms:
Afferent Neurons;Amino Acid Sequence;Amino Acids;Animals;Antibodies;Binding (Molecular Function);Brain;Cell Fraction;Cell Line;Cell surface;Cells;Cercopithecine Herpesvirus 1;Characteristics;Chimera organism;Clinical;Cutaneous;Disease;Endoplasmic Reticulum;Engineering;Figs - dietary;Future;Gel;Gene Transduction Agent;Genes;Glutamate Decarboxylase;Glycoproteins;Hela Cells;Immunohistochemistry;In Vitro;Injection of therapeutic agent;Interphase Cell;Intramuscular;Lentivirus Vector;Limb structure;Membrane;Mus;Muscle;Nerve Growth Factors;Nervous system structure;Neurons;Neurotrophic Tyrosine Kinase Receptor Type 1;Neurotrophin 3;Nociception;Pain;Pain management;Pattern;Peripheral;Population;Population Heterogeneity;Proteins;Publishing;Rabies virus;Rattus;Receptor Signaling;Reporter;Reporting;Research;Resistance;Route;Running;Site;Specificity;Spinal Cord;Spinal Ganglia;Spinal Injections;Sprague-Dawley Rats;Staining method;Stains;Surface;Testing;Therapeutic;Time;Tissues;Toxin;Transfection;Tropism;Viral;Viral Genes;Virion;Virus;Virus Diseases;base;chronic pain;clinical application;fluorophore;gene therapy;immunocytochemistry;in vivo;intradermal injection;nervous system disorder;neurotropic;novel;proenkephalin;rabies virus glycoprotein G;receptor;spinal cord regeneration;spinal nerve posterior root;success;tool;trafficking;vector;virus envelope


application_id: 7577369
project_number: 5R01GM077422-03
project_title: Targeting Nucleic Acids with an Integrated Vitural and Actual Screen
administering_ic: NIGMS
award_notice_date: 2009-01-30
application_type: 5
activity_code: R01
ic: GM
serial_number: 077422
program_official: PREUSCH, PETER
project_start_date: 2007-02-01
project_end_date: 2012-03-31
study_section: Special Emphasis Panel[ZRG1-GGG-J(10)]
contact_pi_person_id: 1863983
contact_pi: CHAIRES, JONATHAN B.
other_pis: Not Applicable
congressional_district: 03
department: INTERNAL MEDICINE/MEDICINE
primary_duns: 057588857
primary_uei: E1KJM4T54MK6
duns_number: 057588857
uei: E1KJM4T54MK6
fips: US
organization_id: 4679701
organization_name: UNIVERSITY OF LOUISVILLE
organization_city: LOUISVILLE
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 402920001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-02-01
project_abstract:
DESCRIPTION (provided by applicant): Nucleic acids are under-represented molecular targets for small molecule therapeutic agents even though recent research shows that unusual nucleic acid structures play a profound role in gene expression and DNA replication. We propose an innovative interdiscplinary high-throughput screening approach for the discovery of new nucleic acid-targeted therapeutic agents. Our approach integrates an actual experimental screening assay with a virtual screening assay. The former is a unique competition dialysis assay that we invented for the discovery of small molecules that target specific nucleic acid sequences or structures. In the competiton dialysis assay an array of designed nucleic acid structures and sequences are dialyzed against a common test ligand solution. At equilibirum more ligand accumulates in the dialysis cell that contains the preferred structure or sequence. The assay is thermodynamically rigorous and allows for quantitative measurement of ligand binding free energies. In our integrated approach an in silico virtual screening assay will be implemented that will contain an array of receptors that is identical to the actual array of nucleic acids used in the competiton dialysis assay. The virtual assay can easily screen millions of compounds for their selective binding to particular nucleic acid structures of functional significance. "Hits" from the virtual screen will be passed to the actual competition dialysis assay for validation. With proposed improvements the competiton dialysis can rapidly screen hundreds of compounds. Our strategy will be to identify libraries of compounds that selectively recognize particular structures with the virtual screen then to rigorously verify these "hits" by high-throughput competition dialysis. Specific plans for the development of the competition dialysis assay include : i) implementation of the assay in a 96-well plate format (facilitating automation) ii) reduction of sample volumes iii) expansion of the biologically significant nucleic acid array and iv) reduction of throughput time. The virtual and actual screens will be fully integrated by an iterative feedback loop to refine the scoring algorithm using actual data obtained from the first generation dialysis assay in which the interaction of 126 compounds with 13 nucleic acids structures was studied. Our approach matches the Road Map Initiative goals by its interdisciplinary approach and by its emphasis on expanding the toolbox available for the discovery of new therapeutics.

project_terms:
Adopted;Algorithms;Antineoplastic Agents;Automation;Base Sequence;Binding (Molecular Function);Biological Assay;Biological Factors;Cancer Biology;Cells;Computer Simulation;Computer software;DNA;DNA Binding;DNA biosynthesis;Data;Data Set;Development;Development Plans;Dialysis procedure;Diamidine;Drug Delivery Systems;Equilibrium;Feedback;Fluorescence;Free Energy;G-Quartets;Gene Expression;Generations;Genetic Transcription;Goals;Hybrids;Intercalating Agents;Laboratories;Lead;Libraries;Ligand Binding;Ligands;Liquid substance;Malignant Neoplasms;Maps;Measurement;Measures;Methods;Molecular;Molecular Target;Nucleic Acid Binding;Nucleic Acids;Nucleic acid sequencing;Paste substance;Phase;Phase I Clinical Trials;Play;Porphyrins;Publishing;Research;Research Personnel;Role;Sampling;Screening procedure;Site;Solutions;Specificity;Structure;System;Telomerase;Testing;Therapeutic Agents;Thermodynamics;Time;Validation;Virtual Library;analytical method;cyanine dye;design;high throughput screening;innovation;intercalation;interdisciplinary approach;interest;novel;novel therapeutics;nucleic acid structure;programs;receptor;repository;small molecule;tool;virtual


application_id: 7577267
project_number: 1R01ES017217-01A2
project_title: Mdig gene and histone demethylation in lung cancer
administering_ic: NIEHS
award_notice_date: 2009-04-18
opportunity_number: PA-07-070
application_type: 1
activity_code: R01
ic: ES
serial_number: 017217
suffix: A2
program_official: QUINN, ASHLINN KO
project_start_date: 2009-05-01
project_end_date: 2014-02-28
study_section: Cancer Etiology Study Section[CE]
contact_pi_person_id: 8832153
contact_pi: CHEN, FEI
other_pis: Not Applicable
congressional_district: 06
department: PHARMACOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
project_abstract:
DESCRIPTION (provided by applicant): Lung cancer is the most common cancer worldwide accounting for 1.3 million cancer deaths annually. Despite extensive efforts to elucidate mechanisms and develop new therapeutic regimens the worldwide mortality rate of lung cancer remains high. Our long- term goal is to understand how mdig gene contributes to the initiation and progression of the human lung cancer and whether mdig can be served as a biomarker and a therapeutic target for lung cancer resulted from exposure to environmental or occupational hazards. The objective of this application is to investigate the role of Mdig protein played on the lung cell proliferation and carcinogenic transformation induced by environmental and occupational hazards/carcinogens. The central hypothesis is that Mdig promotes cell growth and transformation by functioning as a histone demethylase that antagonizes tri-methyl lysine 9 on histone H3. Down-regulation of tri-methyl lysine 9 of histone H3 will enhance the expression of genes associated with the cell cycle regulation and malignant transformation in lung epithelial cells. The rationale behind this proposal is that expression of mdig gene may be critical for lung cell proliferation and carcinogenic transformation in response to environmental carcinogens. To accomplish the objectives of this application we will pursue three specific aims by using cell lines and nude mice as experimental models: (1) test the potential demethylase activity of mdig protein toward tri-methylated lysine 9 on histone H3; (2) determine whether the expression of the cell cycle-regulated genes such as cyclins Cdc25s and checkpoint proteins is regulated by the methylation regulation of mdig; and (3) study the tumorigenic effect of mdig by both over- expression and down-regulation of mdig in BEAS-2B cells and A549 cells respectively in both cell culture and inoculation of the cells in nude mice. At the completion of these specific aims we expect to have determined how mdig contributes to lung cell growth regulation and carcinogenic transformation in response to factors that cause lung cancer. We additionally expect based on preliminary studies that constitutive expression of mdig will compromise the tri-methylation of lysine 9 on histone H3 leading to attenuation of heterochromatin or the formation of other inhibitory epigenetic markers. As a result the expression of genes associated with the cell cycle transition and cell proliferation will be enhanced. Finally in addition to reveal a previously unknown new mechanism of the human lung cancer it is anticipated that expression of mdig can be potentially served as a new biomarker and therapeutic target of the human lung cancer. PUBLIC HEALTH RELEVANCE:  Lung cancer is the leading cause of malignant-related deaths in the United States (US). It kills more Americans than any other type of malignancy. The main cause of lung cancer is the environmental and occupational exposure to carcinogens including tobacco smoking and occupational dust. This project will investigate the mechanism of mdig gene a newly identified lung cancer associated gene in mediating carcinogen-induced lung cancer by testing the hypothesis that mdig inducing cell growth and transformation through down regulation of the tri-methylation of lysine 9 on histone H3 and the heterochromatin formation. The long-term goals are to understand how mdig gene contributes to the initiation and progression of the human lung cancer induced by environmental and occupational hazards to identify biomarkers for early detection of the lung cancer and to develop intervention and prevention strategies.

project_terms:
A549;Accounting;Acute Promyelocytic Leukemia;Affect;Alveolar Macrophages;American;Area;Biological Assay;Carcinogens;Cell Culture Techniques;Cell Cycle;Cell Cycle Progression;Cell Cycle Regulation;Cell Line;Cell Proliferation;Cells;Cessation of life;Characteristics;Cyclins;Disease;Down-Regulation;Dust;Environmental Carcinogens;Environmental and Occupational Exposure;Epigenetic Process;Epithelial Cells;Experimental Models;Exposure to;G1 Phase;Gene Activation;Gene Expression;Gene Expression Regulation;Genes;Genome;Goals;HL-60 Cells;Heterochromatin;Histones;Human;In Vitro;Intervention;Killings;Knockout Mice;Lung;Lung diseases;Lysine;Malignant - descriptor;Malignant Neoplasms;Malignant neoplasm of lung;Measures;Mediating;Mediator of activation protein;Methylation;Minerals;Molecular;Mortality Vital Statistics;Names;Nuclear Antigens;Nucleolar Proteins;Nucleosomes;Nude Mice;Occupational;Oncogene Activation;Outcome;Patients;Peptides;Phase Transition;Play;Prevention strategy;Principal Investigator;Proteins;Regulation;Role;Screening for Lung Cancer;Signal Transduction;Small Interfering RNA;Stream;Testing;Tobacco smoking;Treatment Protocols;United States;Xenopus laevis;attenuation;base;biomarker;cancer therapy;cancer type;cdc Genes;cell growth;cell growth regulation;cell transformation;demethylation;expectation;improved;insight;loss of function;lung carcinogenesis;mass spectrometer;novel therapeutic intervention;novel therapeutics;occupational hazard;outcome forecast;prognostic;programs;public health relevance;response;small hairpin RNA;therapeutic target;tumorigenesis;tumorigenic

public_health_relevance:
Principal Investigator/Program Director (Last first middle): hn eiLung cancer is the leading cause of malignant-related deaths in the United States (US).It kills more Americans than any other type of malignancy. The main cause of lung canceris the environmental and occupational exposure to carcinogens including tobaccosmoking and occupational dust. This project will investigate the mechanism of mdig genea newly identified lung cancer associated gene in mediating carcinogen-induced lungcancer by testing the hypothesis that mdig inducing cell growth and transformation throughdown regulation of the tri-methylation of lysine 9 on histone H3 and the heterochromatinformation. The long-term goals are to understand how mdig gene contributes to the initiationand progression of the human lung cancer induced by environmental and occupationalhazards to identify biomarkers for early detection of the lung cancer and to developintervention and prevention strategies.Public Health Relevance Statement Page


application_id: 7576364
project_number: 1R15GM084431-01A1
project_title: Hydroquinone derivatives as novel calcium ATPase inhibitors
administering_ic: NIGMS
award_notice_date: 2009-09-25
opportunity_number: PA-06-042
application_type: 1
activity_code: R15
ic: GM
serial_number: 084431
suffix: A1
program_official: FABIAN, MILES
project_start_date: 2009-09-30
project_end_date: 2012-08-31
study_section: Macromolecular Structure and Function E Study Section[MSFE]
contact_pi_person_id: 8527958
contact_pi: PAULA, STEFAN FRANZ
other_pis: Not Applicable
congressional_district: 04
department: CHEMISTRY
primary_duns: 072879760
primary_uei: LN53C9E23GH6
duns_number: 072879760
uei: LN53C9E23GH6
fips: US
organization_id: 656601
organization_name: NORTHERN KENTUCKY UNIVERSITY
organization_city: HIGHLAND HEIGHTS
organization_state: KY
organization_type: SCHOOLS OF ARTS AND SCIENCES
organization_zip: 410990001
organization_country: UNITED STATES
project_abstract:
DESCRIPTION (provided by applicant): Inhibitors of the enzyme sarco/endoplasmic reticulum Ca2+ATPase (SERCA) are valuable research tools for the study of the enzyme's role in physiological processes and they also have the potential of being developed into new anti- cancer agents. A series of 25-disubstitued hydroquinones will be synthesized and their ability to inhibit SERCA will be assessed in bioassays. Based on the results computational techniques such as structure-activity relationship modeling and ligand docking will be used to develop models capable of predicting the activities of yet untested hydroquinone-based compounds. With the aid of these models compound libraries will be screened virtually for novel SERCA inhibitors that then will be obtained and tested in bioassays. PUBLIC HEALTH RELEVANCE:  The research described in this application is aimed at the development of novel hydroquinone-based inhibitors of the enzyme sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). As documented by an impressively large number of publications on the naturally occurring inhibitor thapsigargin SERCA inhibitors are of tremendous value for the study of the enzyme's role in physiological processes. In addition it has been shown that SERCA inhibitors can be developed into prodrugs for the treatment of prostate cancer. Since hydroquinone-based compounds are structurally simple and quite different from other SERCA inhibitors their synthesis from inexpensive starting materials is relatively straightforward. Thus they have the potential of being developed into valuable alternatives to currently available agents with unique physicochemical and pharmacodynamic properties.

project_terms:
2-tert-butylhydroquinone;ATP phosphohydrolase;Acylation;Affect;Affinity;Alkylation;Antineoplastic Agents;Apoptosis;Area;Binding (Molecular Function);Binding Sites;Biological Assay;Biological Availability;Ca(2+)-Transporting ATPase;Calcium;Cells;Chemical Structure;Chemicals;Claisen rearrangement;Classification;Collaborations;Collection;Complement;Complex;Computational Technique;Computer Assisted;Computer Simulation;Data;Databases;Development;Discipline;Docking;Drug Design;Endoplasmic Reticulum;Enzyme Inhibitor Drugs;Enzyme Inhibitors;Enzymes;Equilibrium;Esterification;Evaluation;Future;Gambling;Goals;Hand;Homeostasis;Hydrocarbons;Hydroquinones;Knowledge;Length;Libraries;Ligands;Malignant neoplasm of prostate;Measures;Methodology;Methods;Microsomes;Modeling;Modification;Molecular;Molecular Models;Muscle;Organic Synthesis;Oryctolagus cuniculus;Parents;Pharmacodynamics;Pharmacologic Substance;Physiological Processes;Positioning Attribute;Preparation;Prodrugs;Property;Protein Biochemistry;Publications;Quantitative Structure-Activity Relationship;Radioactive;Reaction;Research;Research Methodology;Research Personnel;Role;Route;Scientist;Screening procedure;Series;Specificity;Structure;Structure-Activity Relationship;Students;Techniques;Testing;Thapsigargin;Therapeutic;Training;Ursidae Family;Work;analog;base;cancer cell;career;computerized tools;design;dimethyl sulfate;enzyme activity;experience;high throughput screening;hydroquinone;hydroxyl group;improved;inhibitor/antagonist;interest;intermolecular interaction;methyl iodide;model development;molecular modeling;novel;protein purification;public health relevance;radioligand;receptor;tool;uptake;virtual

public_health_relevance:
The research described in this proposal is aimed at the development of novelhydroquinone-based inhibitors of the enzyme sarco/endoplasmic reticulum Ca2+-ATPase (SERCA). As documented by an impressively large number ofpublications on the naturally occurring inhibitor thapsigargin SERCA inhibitorsare of tremendous value for the study of the enzyme's role in physiologicalprocesses. In addition it has been shown that SERCA inhibitors can bedeveloped into prodrugs for the treatment of prostate cancer. Sincehydroquinone-based compounds are structurally simple and quite different fromother SERCA inhibitors their synthesis from inexpensive starting materials isrelatively straightforward. Thus they have the potential of being developed intovaluable alternatives to currently available agents with unique physicochemicaland pharmacodynamic properties.


application_id: 7575116
project_number: 5R01AG025047-10
project_title: Neuroendocrine mechanisms of reproductive aging
administering_ic: NIA
award_notice_date: 2009-03-26
application_type: 5
activity_code: R01
ic: AG
serial_number: 025047
program_official: MACKIEWICZ, MIROSLAW
project_start_date: 1999-06-01
project_end_date: 2012-03-31
study_section: Neurobiology of Motivated Behavior Study Section[NMB]
contact_pi_person_id: 1891759
contact_pi: JENNES, LOTHAR H
other_pis: Not Applicable
congressional_district: 06
department: ANATOMY/CELL BIOLOGY
primary_duns: 939017877
primary_uei: H1HYA8Z1NTM5
duns_number: 939017877
uei: H1HYA8Z1NTM5
fips: US
organization_id: 2793601
organization_name: UNIVERSITY OF KENTUCKY
organization_city: LEXINGTON
organization_state: KY
organization_type: SCHOOLS OF MEDICINE
organization_zip: 405260001
organization_country: UNITED STATES
arra_indicator: N
budget_start_date: 2009-04-01
project_abstract:
DESCRIPTION (provided by applicant): The overall goals of the proposed research are to determine the changes that occur in the brain during reproductive aging and to reveal the underlying mechanisms that cause a gradual decline in the regularity of the estrous cycle which is followed by a complete cessation of cyclicity in the middle-aged female mouse. The central hypothesis to be tested is that while circulating estradiol levels are normal or slightly elevated in the middle-aged mouse the steroid signal does not reach the GnRH neurons which leads to a low preovulatory LH surge and to an irregular length of the estrous cycle. The present proposal focuses on the glutamatergic neurotransmitter system because it stimulates GnRH releaseit is at least in part regulated by estradiol and its activity or effectiveness is decreased in the middle-aged animal. In addition changes in gene expression in GnRH neurons will be determined during reproductive aging. Specifically  Aim 1: will test the hypothesis that the glutamatergic system does not respond to gonadal steroids during reproductive senescence;  Aim 2: will test the hypothesis that the glutamatergic innervation of GnRH neurons is altered or ineffective during reproductive senescence which leads to a reduced activation of the GnRH neurons during the steroid-induced surge;  Aim 3: will identify changes in gene expression of GnRH neurons changes during reproductive aging.   The proposed studies will provide comprehensive information on the changes that occur in the regulatory input to the GnRH neurons during reproductive aging and will determine which estradiol receptor mediates these changes. A detailed knowledge of these events will help to identify some of the basic mechanisms which underlie the inappropriate interactions between the brain and the ovaries and may provide clues for treatment of disorders that are caused by a central failure to maintain adequate GnRH release.

project_terms:
Age;Aging;Agonist;Animals;Attenuated;Brain;Cells;Data;Diestrus;Disease;Effectiveness;Estradiol;Estradiol Receptors;Estrogen Receptors;Estrous Cycle;Event;Failure (biologic function);Female;Follicle Stimulating Hormone;Funding;Gene Expression;Gene Expression Profile;Genes;Glutamates;Goals;Gonadal Steroid Hormones;Gonadotropin Hormone Releasing Hormone;Hormones;Hypothalamic structure;Knowledge;Length;Literature;Luteinizing Hormone;Measures;Mediating;Messenger RNA;Mus;Neurons;Neurosecretory Systems;Neurotransmitters;Ovary;Ovulation;Pattern;Periodicity;Pituitary Gland;Proestrus;Research;Research Personnel;Rodent;Role;Signal Transduction;Steroids;System;Testing;base;juvenile animal;middle age;nerve supply;noradrenergic;programs;receptor;reproductive;research study;response;senescence


