NIH Article Edition

Research Article

Immune response to immunodominant Mycobacterium tuberculosis antigen ESAT6- derived peptide is HLA-haplotype dependent

 Michele Smart, Marshall Behrens, Luckey David, Catherine Conway, Veena Taneja

The antigenic proteins of Mycobacterium tuberculosis (Mtb) have been defined. We used synthetic peptides of secreted antigens, early secreted antigenic target 6 (ESAT-6) and cultural filtrate protein-10 (CFP-10), of Mtb and characterized the immune response in context of HLA genes. Humanized mice lacking endogenous class II molecules but expressing various human DR and DQ HLA transgenes singly or as a haplotype were used to study the HLA-mediated immune response to peptides.

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Research Article

Hepatic Adaptations to a High Fat Diet in the MRL Mouse Strain are Associated with an Inefficient Oxidative Phosphorylation System
Ahlke Heydemann*,Magdalis González-Vega, Tirsit K. Berhanu, Aaron J. Mull,RagavSharma, and Jenan Holley-Cuthrell

The MRL mice are resistant to a 12-week high fat diet (HFD) feeding protocol, with the proximal cause being an increased basal pAMPKT172 expression in the skeletal muscle. Here, we test if this lack of pathology extends to the liver at both the tissue and cellular levels and its correlation to pAMPKT172 levels. MRL and B6 mice were subjected to 12 weeks of diet intervention and tissues were either fixed for histology or snap-frozen for further processing (n= 3-6, per group).

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Research Article

miRNA-15a, miRNA-15b, and miRNA-499 are Reduced in Erythrocytes of Pre-Diabetic African-American Adults
Maurice B. Fluitt, Namita Kumari, Gail Nunlee-Bland, Sergei Nekhai, Kanwal K. Gambhir*

The genetics of T2DM is complex and not clearly understood. The search for diabetes genes and risk markers is complicated by the heterogeneity of the metabolic disease. Genomewide association studies (GWAS) have identified several genetic variants in association with T2DM. However, since the first T2DM GWAS study, identified genetic variants have been modestly associated with T2DM and account for only about 10% of genetic risk. Further complicating the identification  of genetic biomarkers for T2DM is ethnicity, as genetic variants may be ethnic specific. Additional studies to identify risk markers in the African-American population are needed.

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Research Article

Tau and Pet/Mri Imaging Biomarkers for Detecting and Diagnosing Early Dementia

Yongxia Zhou, Ph.D.*, Bing Bai, and For the Alzheimer’s Disease Neuroimaging Initiative

Specific objective of this project is to quantify the neuropathological tau depositions in brain regions and to investigate primary age-related tau pathology and associations with amyloid and glucose-metabolism, neurocognitive tests and MRI metrics. Preliminary results demonstrated higher temporal deposition especially in the hippocampus and the inferior temporal regions compared to mean cortical deposition. Quantitative Braak stage-based regional analyses found highest tau deposition in the Braak stage II in the preclinical samples.

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Editorial

Quantitative PET/MRI Evaluation and Application in Dementia

Yongxia Zhou, PhD*

A recently introduced integrated scanner combining simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) (PET/MRI) acquisition presents a unique set of opportunities for neuroimaging research and dementia in particular. Among these, the intrinsic co-registration of the images has the potential to reduce errors in multi-modality image registration, which could lead to better quantification of longitudinal volumetric changes in neuroanatomical features that are important for assessing disease progression. PET tracers could provide functional information of brain biochemical processes by radio-labeling specific molecular with high sensitivity and specificity, while MRI could provide superior structural information.

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Research Article 

Pharmacokinetic Exposure and Virologic Response in HIV-1 Infected Pregnant Women Treated with Lopinavir/Ritonavir: Aids Clinical Trials Group

Protocol A5153S: A substudy TO A5150

Beverly E. Sha, MD*, Camlin Tierney, PhD, Xin Sun, MS, Alice Stek. M.D., Susan E. Cohn, M.D., M.P.H., Robert W. Coombs, M.D., Ph.D., Barbara Bastow, B.S.N., Francesca T. Aweeka, Pharm.D, and the AIDS Clinical Trials Group (ACTG) 5153s Team

Current Department of Health and Human Services United States guidelines recommend combination antiretroviral therapy for all pregnant women to prevent perinatal transmission of HIV. Lopinavir/ritonavir (LPV/r) twice daily remains a preferred protease inhibitor (PI) for antiretroviral naïve pregnant women. Drug absorption, distribution, metabolism and excretion constitute the basis of drug pharmacokinetics and may all undergo changes during pregnancy. Changes become increasingly pronounced as pregnancy advances and peak during the third trimester.

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Research Article 

Autonomic Function is Associated with Fitness Level in HIV-Infected Individuals

Morgan H Kocher, MS, ATC, Ronald K Hetzler*, PhD, FACSM , Cecilia M Shikuma, MD, Iris F Kimura, PhD, ATC, PT, Cris D Stickley, PhD, ATC, CSCS , Rachel A Lindsey, PhD, ATC, Beau K Nakamoto, MD, PhD, Dominic C Chow, MD, MPH, PhD

Autonomic dysfunction is a common co-morbidity of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). Decreased autonomic function is linked to increased risk of cardiovascular disease (CVD) and all-cause mortality. This dysfunction is often characterized by increased sympathetic activity, and decreased parasympathetic activity and heart rate variability (HRV).

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Commentary

Addressing Health Disparities in Idiopathic Dilated Cardiomyopathy

Argun D. Can, M.D.*, Steven S. Coughlin, PhD

African Americans are more likely to die from a variety of common chronic diseases including stroke, congestive heart failure, diabetes, hypertension, and major forms of cancer. Previous authors have expressed concern that many blackwhite disparities in morbidity and mortality from chronic diseases have not diminished in the United States in recent decades despite concerted efforts to address them.

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Research Article

Community-Based Participatory Research Studies on HIV/AIDS Prevention, 2005- 2014

Steven S Coughlin*

The recent literature on community-based participatory research (CBPR) approaches to preventing HIV infection in diverse communities was systematically reviewed as part of the planning process for a new study. Published HIV prevention studies that employed CBPR methods were identified for the period January 1, 2005 to April 30, 2014 using PubMed databases and MeSH term and keyword searches.

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Research Article

A Review of Smartphone Applications for Promoting Physical Activity

Steven S. Coughlin*, Mary Whitehead, Joyce Q. Sheats, Jeff Mastromonico, Selina Smith

Sedentary behavior and physical activity are important public health issues. Approximately one-third of adults in the U.S. are physically inactive. The increasing prevalence of obesity in the U.S. and many other countries and the independent association of obesity with several forms of cancer, cardiovascular disease, diabetes and other forms of chronic illness have prompted interest in identifying efficacious ways to promote physical activity and reduce obesity.

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Letter to the Editor
Delays in Patient Waiting Times at U.S. Department of Veterans Affairs Hospitals in Cities with Sizeable Hispanic Populations
Steven S. Coughlin* 

The systemic problems that have plagued the U.S. Department of Veterans Affairs (VA), including the use of bogus waiting lists for Veterans seeking care at VA healthcare facilities and other lapses in organizational ethics and personal integrity, have prompted an audit by the VA, an investigation by the VA Office of Inspector General, and efforts by the U.S. House of Representatives and U.S. Senate to assist Veterans by reforming the Department. However, the information released by the VA and recent Congressional testimony neglects an important facet of this situation. VA healthcare facilities located in cities with sizeable Hispanic populations are less likely to have scheduled patient visits within 30 days.

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Research Article

EPA Leadership on Science, Innovation, and Decision Support Tools for Addressing Current and Future Challenges

Alan D. Hecht*, Aaron Ferster, Kevin Summers

When the U.S. Environmental Protection Agency (EPA) was established nearly 50 years ago, the nation faced serious threats to its air, land, and water, which in turn impacted human health. These threats were effectively addressed by the creation of EPA (in 1970) and many subsequent landmark environmental legislations which in turn significantly reduced threats to the Nation’s environment and public health.

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Editorial 
KERATOCONUS: IN VITRO AND IN VIVO

Karamichos D*

Keratoconus (KC) is a degenerative disease of the front part of the eye, named cornea. KC has three major characteristics: 1) cornea thinning, 2) corneal bulging, and 3) corneal scarring. KC usually appears during puberty and can quickly progress to severe stages leading to blindness. Worldwide 1:2000 people are affected with more prominence in the South Asians, Eastern  Mediterranean and North African populations. Despite significant efforts by corneal researchers, the pathophysiology of the disease is still unknown, due in part to the absence of an animal  model that can replicate KC.

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Empirical Research

Screening Child Social-emotional and Behavioral Functioning in Low-Income African Country Contexts

Janet Nakigudde, Besa Bauta, Sharon Wolf, Keng-Yen Huang*

Increased attention is being paid to identifying and responding to the social-emotional and behavioral needs of children in low-income countries (LICs). Currently, there is little information available on the use of brief screening instruments in LICs. The lack of psychometrically sound brief assessment tools creates a challenge in determining the population prevalence of child social-emotional and behavioral risk burden in Sub-Saharan African (SSA) country contexts. This study sought to determine the reliability and validity of three brief parent-rated screening tools-the Social Competence Scale (SCS), Pictorial Pediatric Symptom Checklist (PPSC), and the Strengths and Difficulties Questionnaire (SDQ)-in Uganda.

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Research article

Bleomycin-Induced Neonatal Lung Injury Requires the Autocrine Pulmonary Angiotensin System

Abdellatif Abdelwahab, Indiwari Gopallawa, Christopher C. Piasecki, Ira H. Gewolb and Bruce D. Uhal*

Previous work from this laboratory demonstrated that apoptosis is regulated by a local angiotensin (ANG) system in alveolar epithelial cells (AECs). Autocrine generation of angiotensin II (ANGII) in response to endogenous or xenobiotic inducers is required for apoptosis in adult rat AECs and in AEC-derived human lung carcinoma cell line A549. Therefore, we hypothesized that a similar mechanism might also be involved in bleomycin (Bleo)-induced murine neonatal lung injury.

 

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Research Article 

Favourable Prognosis when Lung-Cancer Patients with Superior Vena Cava Obstruction (SVCO) are Referred Promptly to EBUS-TBNA Prior to Medical or Surgical Management

Leon G. D’Cruz*, Bassam Younes, F. Anthony Lai, Syed Arshad Husain

Primary care patients with superior vena cava obstruction (SVCO) syndrome are usually referred to emergency departments for urgent medical management (high-dose corticosteroids to reduce inflammation), pre-biopsy radiotherapy and/or stent placements to restore patency to the vessel. Biopsy, diagnosis and staging of the mediastinal mass is often postponed until resolution of SVCO symptoms. However, lung cancers metastasise rapidly and delays can influence the eventual outcome of patients. An additional merit in treating SVCO symptoms post-biopsy is that high-dose corticosteroids and pre-biopsy radiotherapy will degrade the quality of biopsy specimens, complicating diagnosis and subsequent management.

 

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Research Article

Modulation of Immune Response by Ultra-Violet Light in HLA Class-II Transgenic Mice

Daniel Bastardo Blanco, David Luckey, Michele Smart, Mark Pittelkow, Rajiv Kumar, Chella S David, and Ashutosh K Mangalam *

Multiple Sclerosis (MS) is a chronic and debilitating disease of the central nervous system linked to both genetic and environmental factors. Among the genetic factors, MHC, especially HLA class-II, is strongly  associated with  predisposition to MS. Although  in vitro studies  have helped us  understand some  aspects of HLA class-II  association with the disease,  performing in vivo  analysis is necessary in order to further understand this correlation. Studying the role of class-II genes in vivo is a difficult task due to the heterogeneity of human population, the complexity of MHC, and the strong linkage disequilibrium among different class-II genes.

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Research Article
Dust Allergens within Rural Northern Rocky Mountain Residences

Emily Weiler BS, Erin Semmens PhD, Curtis Noonan PhD, Carol Cady MD, and Tony Ward PhD*

To date, few studies have characterized allergens within residences located in rural areas of the northern Rocky Mountain region. In this study, we collected dust samples from 57 homes located throughout western Montana and northern Idaho. Dust samples were collected and later analyzed for dust mite allergens Der f 1 and Der p 1, Group 2 mite allergens (Der p 2 and Der f 2), domestic feline (Fel d 1), and canine (Can f 1). Indoor temperature and humidity levels were also measured during the sampling program, as were basic characteristics of each home.

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Research Article

Immune Response to Immunodominant Mycobacterium tuberculosis Antigen ESAT6- Derived Peptide is HLA-Haplotype Dependent

Michele Smart, Marshall Behrens, Luckey David, Catherine Conway, Veena Taneja*

The antigenic proteins of Mycobacterium tuberculosis (Mtb) have been defined. We used synthetic peptides of secreted antigens, early secreted antigenic target 6 (ESAT-6) and cultural filtrate protein-10 (CFP-10), of Mtb and characterized the immune response in context of HLA genes. Humanized mice lacking endogenous class II molecules but expressing various human DR and DQ HLA transgenes singly or as a haplotype were used to study the HLA-mediated immune response to peptides. Our observations showed that the overall response to the promiscuous ESAT-6 31-45 peptide may be dependent on the HLA haplotype rather than a single DR or DQ molecule.

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Research Article  

Engineered Production of Tryprostatins in E. coli through Reconstitution of a Partial  ftm Biosynthetic Gene Cluster fromAspergillus sp.

Gopitkumar R Shah# Shane R. Wesener# and Yi-Qiang Cheng*

Tryprostatin A and B are indole alkaloid-based fungal products that inhibit mammalian cell cycle at the G2/M phase. They are biosynthetic intermediates of fumitremorgins produced by a complex pathway involving a nonribosomal peptide synthetase (FtmA), a prenyltransferase (FtmB), a cytochrome P450 hydroxylase (FtmC), an O-methyltransferase (FtmD), and several additional enzymes.

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Short Paper 

Isolation and Structural Characterization of Glycosaminoglycans from Heads of Red Salmon (Oncorhynchus nerka)

Fuming Zhang* , Jin Xie,  Robert J. Linhardt

Glycosaminoglycans (GAGs) are linear, highly negatively charged polysaccharides. They are ubiquitous molecules exhibiting a wide range of biological functions with numerous applications in pharmaceutical, cosmetic, and nutraceutical industrials. The commercial fish-processing industry generates large quantities of solid waste, which can represent a potential resource for GAG production. In this study, we used a three-step recovery and purification scheme for isolation of GAGs from the heads of red salmon (Oncorhynchus nerka).

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Review Article
Smartphone Applications for Promoting Healthy Diet and Nutrition: A Literature Review
Steven S. Coughlin, PhD*, Mary Whitehead, MPH, CHES, Joyce Q. Sheats, RN, MPH, Jeff Mastromonico, Dale Hardy, PhD, RD, LD, CDE, CHES, Selina A. Smith, PhD, MDiv

Rapid developments in technology have encouraged the use of smartphones in health promotion research and practice. Although many applications (apps) relating to diet and nutrition are available from major smartphone platforms, relatively few have been tested in research studies in order to determine their effectiveness in promoting health. In this article, we summarize data on the use of smartphone applications for promoting healthy diet and nutrition based upon bibliographic searches in PubMed and CINAHL with relevant search terms pertaining to diet, nutrition, and weight loss through August 2015.

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Brief Report

Developing a Cookbook with Lifestyle Tips: A Community-Engaged Approach to Promoting Diet-Related Cancer Prevention Guidelines

Selina A. Smith, PhD, MDiv, Joyce Q. Sheats, RN, MPH, Mary S. Whitehead, MPH, CHES, Ernestine Delmoor, MPH, Thomas Britt, MD, MPH, Cassandra L. Harris, MS, MCHES, Janette Robinson-Flint, L. Monique Porche- Smith, MS, Kayellen Edmonds Umeakunne, MS, RD, LD, and Steven S. Coughlin, PhD

Supplementing nutrition education with skills-building activities may enhance community awareness of diet-related cancer prevention guidelines. To develop a cookbook with lifestyle tips, recipes were solicited from the National Black Leadership Initiative on Cancer (NBLIC) community coalitions and dietary intake advice from participants in the Educational Program to Increase Colorectal Cancer Screening (EPICS). With guidance from a chef and registered dietitian, recipes were tested, assessed, and transformed; lifestyle advice was obtained from focus groups

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Case Report

Infantile Growth Hormone Deficiency and X- Linked Adrenal Hypoplasia Congenita

Stephanie T. Chung*, Carolyn H. Chi, Morey W. Haymond, George S, Jeha

X-linked adrenal hypoplasia congenita (AHC) is a rare but important cause of primary adrenal insufficiency and can be associated with significant morbidity and mortality. AHC is caused by mutations within the NROB1 gene that codes for the DAX-1 protein, an orphan nuclear receptor essential for the development of the hypothalamic-pituitary-adrenal axis. Affected individuals typically present in early infancy with adrenal insufficiency and growth is usually normal once medical therapy is instituted. Here we report the first case of growth hormone deficiency in an infant with AHC and a novel NR0B1 missense mutation.

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Review Article

Gold Nanoparticles for Radiation Enhancement in Vivo

Samana Shrestha, Leon N Cooper, Oleg A. Andreev, Yana K. Reshetnyak and Michael P. Antosh*

Enhancing the effect of radiation on tumors would be a significant improvement in radiation therapy. With radiation enhancement, less radiation could be used to achieve the same goals, lessening damage to healthy tissue and lessening side effects. Gold nanoparticles are a promising method for achieving this enhancement, particularly when the gold nanoparticles are targeted to cancer. This literature review discusses the properties of gold nanoparticles as well as existing in vivo radiation enhancement results using both targeted and non-targeted gold nanoparticles.

 

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Editorial

A Perspective on Chromosomal Double Strand Break Markers in Mammalian Cells

Haibo Wang, Sanjay Adhikari, Brian E. Butler, Tej K. Pandita, Sankar Mitra, and Muralidhar L. Hegde*

The DNA damage response (DDR) in mammalian cells is a complex and highly orchestrated signaling process that regulates the recruitment of specific DDR proteins to the DNA damage sites. The most lethal type of DNA damage is the double-strand break (DSB), which is generated by ionizing radiation (IR), radiomimetic drugs and also drugs of DNA topoisomerase 2 poison family. DSBs are also endogenously caused during replication of single-strand breaks generated by reactive oxygen species or at stalled replication forks.                                               

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Research Article

Interobserver and Intermodality Variability in GTV Delineation on Simulation CT,FDG- PET, and MR Images of Head and Neck Cancer

Carryn M. Anderson*, Wenqing Sun, John M. Buatti, Joan E. Maley, Bruno Policeni, Sarah L. Mott, John E. Bayouth

To compare the interobserver and intermodality differences in image-based identification of head and neck primary site gross tumor volumes (GTV). Modalities compared include: contrast-enhanced CT, F-18 fluorodeoxyglucose positron emission tomography (PET/CT) and contrast-enhanced MRI.         

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