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Community-Based Participatory Clinical Research in Obesity by Adolescents: Pipeline for Researchers of the FutureEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe a pilot model in which adolescents apply principles of Community-Based Participatory Research (CBPR) at the epicenter of the obesity diabetes epidemic in rural Appalachia in West Virginia. The model invites minority, financially disadvantaged, and educationally disadvantaged adolescents to become educated on ethics, then provides infrastructure to support study design and conduct of CBPR. This experience demonstrates that these adolescents can effi ciently, with quality and integrity, reach into the most vulnerable of communities and their own families to show that the prevalence of obesity is at 50% and diabet...
Source: Clinical and Translational Science - October 26, 2009 Category: Biomedical Science Authors: Robert Branch, Ann Chester Source Type: journals

Feasibility of Adolescents to Conduct Community-Based Participatory Research on Obesity and Diabetes in Rural AppalachiaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe a novel approach applied to obesity management and diabetes prevention. This takes advantage of a network of science clubs organized by the Health Sciences and Technology Academy (HSTA) for extracurricular activity of disadvantaged high school students in rural Appalachia. Physician scientists and educators provided an intensive summer course on CBPR, ethics, and study design on obesity management and diabetes prevention. Ethical certification for CBPR investigation was obtained for 210 students and 18 mentors for a study on the prevalence of obesity and Type II diabetes within their community. Over a 6-month p...
Source: Clinical and Translational Science - October 26, 2009 Category: Biomedical Science Authors: Genevieve Bardwell, Cathy Morton, Ann Chester, Petr Pancoska, Shama Buch, Alfred Cecchetti, Marcella Vecchio, Stephanie Paulsen, Stephen Groark, Robert A. Branch Source Type: journals

The Washington University Institute for Clinical and Translational SciencesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Clinical and Translational Science)
Source: Clinical and Translational Science - October 26, 2009 Category: Biomedical Science Authors: Bradley Evanoff, Linda Cottler, Rakesh Nagarajan, Jane Garbutt, Kenneth Polonsky Source Type: journals

The Future of Biotechnology FundingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Clinical and Translational Science)
Source: Clinical and Translational Science - October 26, 2009 Category: Biomedical Science Authors: Elaine Musgrave Source Type: journals

What Can Be Done to Protect the Translational Investigator?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Clinical and Translational Science)
Source: Clinical and Translational Science - October 26, 2009 Category: Biomedical Science Authors: Karl E. Anderson Source Type: journals

In the NEWS A QUICK ROUNDUP OF NEWS AND INFORMATION FROM OUR COMMUNITYEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Clinical and Translational Science)
Source: Clinical and Translational Science - October 26, 2009 Category: Biomedical Science Authors: Barbara Boughton Source Type: journals

Bring Business Lessons to CTSEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Clinical and Translational Science)
Source: Clinical and Translational Science - October 26, 2009 Category: Biomedical Science Authors: Arthur M. Feldman Source Type: journals

Thrombotic Microangiopathies: Multimers, Metalloprotease, and BeyondEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The pathophysiology of various types of thrombotic microangiopathies is coming progressively into focus. Therapeutic advances are likely to follow at a quickening pace. This discussion focuses on thrombotic thrombocytopenic purpura (TTP), the hemolytic-uremic syndrome (HUS), thrombotic microangiopathies associated with transplantation-immunosuppression or anti-angiogenesis therapy, and the preeclampsia/hemolysis-elevated liver enzymes and low platelets syndrome (HELLP). (Source: Clinical and Translational Science)
Source: Clinical and Translational Science - October 7, 2009 Category: Biomedical Science Authors: Joel Moake Source Type: journals

Meta-analysis: A Brief IntroductionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Meta-analysis is the process of combining data from multiple sources and analyzing it together to increase power and provide a clearer picture of the effect of intervention or exposure on an outcome. The process is not complicated, but requires a great deal of attention to detail. A specific set of inclusion criteria for studies must be defined. Published or available study results may be affected by publication bias of several different types, so the researcher should be sure to conduct a thorough search of available databases in order to include unpublished findings. Following selection, the group of studies should be ex...
Source: Clinical and Translational Science - October 6, 2009 Category: Biomedical Science Authors: Jocelyn A. Andrel, Scott W. Keith, Benjamin E. Leiby Source Type: journals

From Research to Public Policy: An Essential Extension of the Translation Research AgendaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Research translation typically includes translation from basic science into clinical research and from clinical research into everyday clinical practice. In this essay, we propose a greater emphasis on applying research findings, both basic and clinical, into effective public policies that promote health. Research can have important influences on policy by providing a scholarly basis for action research, and translation science units within academic health centers are in powerful positions to build bridges between the research and policy making communities to promote the development of evidence based policy. The results wi...
Source: Clinical and Translational Science - October 5, 2009 Category: Biomedical Science Authors: David M. Mirvis Source Type: journals

Targeted Disruption of KATP Channels Aggravates Cardiac Toxicity in Cocaine AbuseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study therefore reveals a previously unrecognized role of Kir6.2-encoded KATP channels in determining cardiovascular outcome in chronic cocaine abuse, identifying a novel molecular determinant of cocaine cardiotoxicity. (Source: Clinical and Translational Science)
Source: Clinical and Translational Science - October 5, 2009 Category: Biomedical Science Authors: Santiago Reyes, Garvan C. Kane, Leonid V. Zingman, Satsuki Yamada, Andre Terzic Source Type: journals

Experimental Therapeutics: A Paradigm for Personalized MedicineEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Clinical and Translational Science)
Source: Clinical and Translational Science - October 5, 2009 Category: Biomedical Science Authors: Scott A. Waldman, Walter K. Kraft, Timothy J. Nelson, Andre Terzic Source Type: journals

Creating an Ontology-Based Human Phenotyping System: The Rockefeller University Bleeding History ExperienceEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The lack of standardized methods for human phenotyping is a major obstacle in translational science. We have developed a bleeding history phenotyping system comprising an ontology, a questionnaire, a Web-based phenotype recording instrument (PRI), and a database. The ontology facilitates transparency, collaboration, aggregation of data, and data analysis. The integrated system allows investigators worldwide to use the PRI, add their de-identified data to the database, and query the aggregated data. Thus, this system can increase the power to detect genotype[ndash]phenotype[ndash]environment relationships and help new inves...
Source: Clinical and Translational Science - October 5, 2009 Category: Biomedical Science Authors: Andreas C. Mauer, Edward M. Barbour, Nickolay A. Khazanov, Natasha Levenkova, Shamim A. Mollah, Barry S. Coller Source Type: journals

Imprinting Status of GαS, NESP55, and XLαs in Cell Cultures Derived from Human Embryonic Germ Cells: GNAS Imprinting in Human Embryonic Germ CellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
GNAS is a complex gene that through use of alternative first exons encodes signaling proteins G[alpha]s and XL[alpha]s plus neurosecretory protein NESP55. Tissue-specific expression of these proteins is regulated through reciprocal genomic imprinting in fully differentiated and developed tissue. Mutations in GNAS account for several human disorders, including McCune-Albright syndrome and Albright hereditary osteodystrophy, and further knowledge of GNAS imprinting may provide insights into variable phenotypes of these disorders. We therefore analyzed expression of G[alpha]s, NESP55, and XL[alpha]s prior to tissue differenti...
Source: Clinical and Translational Science - October 5, 2009 Category: Biomedical Science Authors: Janet L. Crane, Michael J. Shamblott, Joyce Axelman, Stephanie Hsu, Michael A. Levine, Emily L. Germain-Lee Source Type: journals

Neutrophil Elastase Increases Airway Epithelial Nonheme Iron LevelsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Alpha-1-antitrypsin (A1AT) deficiency is characterized by increased neutrophil elastase (NE) activity and oxidative stress in the lung. We hypothesized that NE exposure generates reactive oxygen species by increasing lung nonheme iron. To test this hypothesis, we measured bronchoalveolar lavage (BAL) iron and ferritin levels, using inductively coupled plasma (ICP) optical emission spectroscopy and an ELISA, respectively, in A1AT-deficient patients and healthy subjects. To confirm the role of NE in regulating lung iron homeostasis, we administered intratracheally NE or control buffer to rats and measured BAL and lung iron a...
Source: Clinical and Translational Science - October 5, 2009 Category: Biomedical Science Authors: Bernard M. Fischer, Denise A. Lopez Domowicz, Shuo Zheng, Jamie L. Carter, N. Gerry McElvaney, Clifford Taggart, James R. Lehmann, Judith A. Voynow, Andrew J. Ghio Source Type: journals

Increased Phosphorylation-Dependent Nuclear Export of Class II Histone Deacetylases in Failing Human HeartEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, human left ventricular tissue from nonfailing and failing adult hearts was analyzed for the presence of MEF2, HDACs 4 and 5. CaMK and HDAC kinase activities were measured in tissue homogenates. In nuclear fractions from failing ventricles, HDAC4 and HDAC5 protein was decreased versus nonfailing controls. MEF2 was not reduced in failing nuclear fractions. CaMK and HDAC kinase activities were increased in failing versus nonfailing hearts. PKC[mu] (PKD1) activity was increased in nuclear fractions from failing human LVs. These data provide support for decreased nuclear compartment class II HDACs in the FHH, ass...
Source: Clinical and Translational Science - September 10, 2009 Category: Biomedical Science Authors: Mihail B. Calalb, Timothy A. McKinsey, Scott Newkirk, Khai Huynh, Carmen C. Sucharov, Michael R. Bristow Source Type: journals

Isosorbide Dinitrate and Hydralazine as Therapy for African Americans with Heart Failure; a Failed Paradigm?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Clinical and Translational Science)
Source: Clinical and Translational Science - August 6, 2009 Category: Biomedical Science Authors: Clyde W. Yancy, Arthur Feldman Source Type: journals

Lymphocyte-Bound Complement Activation Products as Biomarkers for Diagnosis of Systemic Lupus ErythematosusEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Systemic lupus erythematosus (SLE) is frequently misdiagnosed due to the lack of definitive diagnostic tests. The purpose of this study was to determine specifically whether complement activation products (CAP) are deposited on lymphocytes of SLE patients and whether lymphocyte-bound CAP (LB-CAP) may serve as novel biomarkers for the diagnosis of SLE. We conducted a cross-sectional study of 224 patients with SLE, 179 patients with other diseases, and 114 healthy controls. LB-CAP on peripheral blood lymphocytes was measured by flow cytometry. Diagnostic utility of LB-CAP was determined by receiver operating characteristic (...
Source: Clinical and Translational Science - July 31, 2009 Category: Biomedical Science Authors: Chau-Ching Liu, Amy H. Kao, Douglas M. Hawkins, Susan Manzi, Abdus Sattar, Nicole Wilson, Joseph M. Ahearn Source Type: journals

Phenotyping the Right Ventricle in Patients with Pulmonary HypertensionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Right ventricular (RV) failure is associated with poor outcomes in pulmonary hypertension (PH). We sought to phenotype the RV in PH patients with compensated and decompensated RV function by quantifying regional and global RV structural and functional changes. Twenty-two patients (age 51 ± 11, 14 females, mean pulmonary artery (PA) pressure range 13[ndash]79 mmHg) underwent right heart catheterization, echocardiography, and ECG-gated multislice computed tomography of the chest. Patients were divided into three groups: Normal, PH with hemodynamically compensated, and decompensated RV function (PH-C and PH-D, respectively)....
Source: Clinical and Translational Science - July 30, 2009 Category: Biomedical Science Authors: Marc A. Simon, Christopher Deible, Michael A. Mathier, Joan Lacomis, Orly Goitein, Sanjeev G. Shroff, Michael R. Pinsky Source Type: journals

Trachea Epithelium as a "Canary" for Cigarette Smoking-Induced Biologic Phenotype of the Small Airway EpitheliumEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The initial site of smoking-induced lung disease is the small airway epithelium, which is difficult and time consuming to sample by fiberoptic bronchoscopy. We developed a rapid, office-based procedure to obtain trachea epithelium without conscious sedation from healthy nonsmokers (n= 26) and healthy smokers (n= 19, 27 ± 15 pack-year). Gene expression differences (fold change >1.5, p < 0.01, Benjamini[ndash]Hochberg correction) were assessed with Affymetrix microarrays. A total of 1,057 probe sets were differentially expressed in healthy smokers versus nonsmokers, representing >500 genes. Trachea gene expression was compa...
Source: Clinical and Translational Science - July 29, 2009 Category: Biomedical Science Authors: Meredith L. Turetz, Timothy P. O'Connor, Ann E. Tilley, Yael Strulovici-Barel, Jacqueline Salit, David Dang, Matthew Teater, Jason Mezey, Andrew G. Clark, Ronald G. Crystal Source Type: journals

Single Cell Analysis of Complex Thymus Stromal Cell Populations: Rapid Thymic Epithelia Preparation Characterizes Radiation InjuryEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We present a new rapid separation technique that yields consistent viable TEC numbers in a quarter of the prior preparation time. Using this new procedure, we identify changes in stromal populations following total body irradiation (TBI). By flow cytometry, we show that TBI significantly depletes UEA+ medullary TEC, while sparing Ly51+ CD45[minus] cells. Further characterization of the Ly51+ subset reveals enrichment of fibroblasts (CD45[minus] Ly51+ MHCII[minus]), while cortical TECs (CD45[minus] Ly51+ MHCII+) were markedly reduced. Dendritic cells (CD11c+ CD45+) were also decreased following TBI. These data suggest that ...
Source: Clinical and Translational Science - July 15, 2009 Category: Biomedical Science Authors: Kirsten M. Williams, Heather Mella, Philip J. Lucas, Joy A. Williams, William Telford, Ronald E. Gress Source Type: journals

Defining the Components of the Research PipelineEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The National Institutes of Health (NIH) has proposed that research moves from "bench to bedside" through a Pipeline consisting of distinct research categories bridged by bidirectional translation. The original NIH Pipeline has now been expanded to include practice- and community-based research. We developed operational definitions for the elements along the expanded NIH Pipeline. The proposed definitions were pilot-tested and refined using the Computer Retrieval of Information on Scientific Projects (CRISP) and the Secure Internet-Linked Web Technologies (SILK) database containing funding information for individual NIH awa...
Source: Clinical and Translational Science - July 14, 2009 Category: Biomedical Science Authors: Michael S. Kleinman, James W. Mold Source Type: journals

Identification of Biomarkers in Human Head and Neck Tumor Cell Lines That Predict For In Vitro Sensitivity to GefitinibEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Potential biomarkers were identified for in vitro sensitivity to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib in head and neck cancer. Gefitinib sensitivity was determined in cell lines, followed by transcript profiling coupled with a novel pathway analysis approach. Eleven cell lines were highly sensitive to gefitinib (inhibitor concentration required to give 50% growth inhibition [GI50] < 1 [mu]M), three had intermediate sensitivity (GI50 1[ndash]7 [mu]M), and six were resistant (GI50 > 7 [mu]M); an exploratory principal component analysis revealed a separation between the genomic profi...
Source: Clinical and Translational Science - June 24, 2009 Category: Biomedical Science Authors: D. Mark Hickinson, Gayle B. Marshall, Garry J. Beran, Marileila Varella-Garcia, Elizabeth A. Mills, Marie C. South, Andrew M. Cassidy, Kerry L Acheson, Gael McWalter, Rose M. McCormack, Paul A. Bunn, Tim French, Alex Graham, Brian R. Holloway, Fred R. Hir Source Type: journals

Stem Cell Platforms for Regenerative MedicineEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The pandemic of chronic degenerative diseases associated with aging demographics mandates development of effective approaches for tissue repair. As diverse stem cells directly contribute to innate healing, the capacity for de novo tissue reconstruction harbors a promising role for regenerative medicine. Indeed, a spectrum of natural stem cell sources ranging from embryonic to adult progenitors has been recently identified with unique characteristics for regeneration. The accessibility and applicability of the regenerative armamentarium has been further expanded with stem cells engineered by nuclear reprogramming. Through s...
Source: Clinical and Translational Science - May 7, 2009 Category: Biomedical Science Authors: Timothy J. Nelson, Atta Behfar, Satsuki Yamada, Almudena Martinez-Fernandez, Andre Terzic Source Type: journals

Ca2+-Binding Proteins in Dogs with Heart Failure: Effects of Cardiac Contractility Modulation Electrical SignalsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusion: CCM therapy restores LV expression of S100A1, PS2, and sorcin. Normalization of CBPs may partly contribute to improved LV function in HF following CCM therapy. (Source: Clinical and Translational Science)
Source: Clinical and Translational Science - May 7, 2009 Category: Biomedical Science Authors: Ramesh C. Gupta, Sudhish Mishra, Sharad Rastogi, Mengjum Wang, Benny Rousso, Yuval Mika, Andrew Remppis, Hani N. Sabbah Source Type: journals

Tissue-Level Modeling of Xenobiotic Metabolism in Liver: An Emerging Tool for Enabling Clinical Translational ResearchEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This review summarizes some of the recent developments and identifies critical challenges associated with in vitro and in silico representations of the liver and assesses the translational potential of these models in the quest of rationalizing the process of evaluating drug efficacy and toxicity. It discusses a wide range of research efforts that have produced, during recent years, quantitative descriptions and conceptual as well as computational models of hepatic processes such as biotransport and biotransformation, intra- and intercelular signal transduction, detoxification, etc. The abovementioned research efforts cove...
Source: Clinical and Translational Science - March 13, 2009 Category: Biomedical Science Authors: Marianthi G. Lerapetritou, Panos G. Georgopoulos, Charles M. Roth, Loannis P. Androulakis Source Type: journals

Inhibition of Protein 4.1 R and NuMA Interaction by Mutagenization of Their Binding-Sites Abrogates Nuclear Localization of 4.1 REmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Protein 4.1R(4.1R) is a multifunctional structural protein recently implicated in nuclear assembly and cell division. We earlier demonstrated that 4.1R forms a multiprotein complex with mitotic spindle and spindle pole organizing proteins, such as NuMA, dynein, and dynactin, by binding to residues 1788[ndash]1810 of NuMA through amino acids encoded by exons 20 and 21 in 24 kD domain. Employing random-and site-directed mutagenesis combined with glycine- and alanine-scanning, we have identified amino acids of 4.1 R and NuMA that sustain their interaction, and have analyzed the effect of mutating the binding sites on their in...
Source: Clinical and Translational Science - January 31, 2009 Category: Biomedical Science Authors: Subhendra N. Mattagajasingh, Shu-Ching Huang, Edward J. Benz Jr Source Type: journals

Molecular Diagnostics at the Nexus of Individualized Medicine, Healthcare Delivery, and Public PolicyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: Clinical and Translational Science)
Source: Clinical and Translational Science - October 23, 2008 Category: Biomedical Science Authors: Scott A. Waldman, Andre Terzic Source Type: journals