Digital Commons Network^™

Diurnal Variation Of The Human Adipose Transcriptome And The Link To Metabolic Disease., Andrey Loboda, Walter K. Kraft, Bernard Fine, Jeffrey Joseph, Michael Nebozhyn, Chunsheng Zhang, Yudong He, Xia Yang, Christopher Wright, Mark Morris, Ira Chalikonda, Mark Ferguson, Valur Emilsson, Amy Leonardson, John Lamb, Hongyue Dai, Eric Schadt, Howard E. Greenberg, Pek Yee Lum

Department of Anesthesiology Faculty Papers

ABSTRACT: BACKGROUND: Circadian (diurnal) rhythm is an integral part of the physiology of the body; specifically, sleep, feeding behavior and metabolism are tightly linked to the light-dark cycle dictated by earth's rotation. METHODS: The present study examines the effect of diurnal rhythm on gene expression in the subcutaneous adipose tissue of overweight to mildly obese, healthy individuals. In this well-controlled clinical study, adipose biopsies were taken in the morning, afternoon and evening from individuals in three study arms: treatment with the weight loss drug sibutramine/fasted, placebo/fed and placebo/fasted. RESULTS: The results indicated that diurnal rhythm was the most significant driver …

Facilitated Monocyte-Macrophage Uptake And Tissue Distribution Of Superparmagnetic Iron-Oxide Nanoparticles., Arnaud Beduneau, Zhiya Ma, Cassi B. Grotepas, Alexander Kabanov, Barrett E. Rabinow, Nan Gong, R. Lee Mosley, Huanyu Dou, Michael D. Boska, Howard Gendelman

Journal Articles: Radiology

BACKGROUND: We posit that the same mononuclear phagocytes (MP) that serve as target cells and vehicles for a host of microbial infections can be used to improve diagnostics and drug delivery. We also theorize that physical and biological processes such as particle shape, size, coating and opsonization that affect MP clearance of debris and microbes can be harnessed to facilitate uptake of nanoparticles (NP) and tissue delivery.

METHODS: Monocytes and monocyte-derived macrophages (MDM) were used as vehicles of superparamagnetic iron oxide (SPIO) NP and immunoglobulin (IgG) or albumin coated SPIO for studies of uptake and distribution. IgG coated SPIO was …

Genetic Contribution To Patent Ductus Arteriosus In The Premature Newborn, Naveed Hussain

Articles - Patient Care

BACKGROUND The most common congenital heart disease in the newborn population, patent ductus arteriosus, accounts for significant morbidity in preterm newborns. In addition to prematurity and environmental factors, we hypothesized that genetic factors play a significant role in this condition. OBJECTIVE The objective of this study was to quantify the contribution of genetic factors to the variance in liability for patent ductus arteriosus in premature newborns. PATIENTS AND METHODS A retrospective study (1991–2006) from 2 centers was performed by using zygosity data from premature twins born at ≤36 weeks’ gestational age and surviving beyond 36 weeks’ postmenstrual age. Patent ductus …

Alcohol In Moderation, Cardioprotection And Neuroprotection : Epidemiological Considerations And Mechanistic Studies, Dipak K. Das Dr.

UCHC Articles - Research

In contrast to many years of important research and clinical attention to the pathological effects of alcohol (ethanol) abuse, the past several decades have seen the publication of a number of peer-reviewed studies indicating beneficial effects of light-moderate, non-binge consumption of varied alcoholic beverages, as well as experimental demonstrations that moderate alcohol exposure can initiate typically cytoprotective mechanisms. A considerable body of epidemiology associates moderate alcohol consumption with significantly reduced risks of coronary heart disease and, albeit currently a less robust relationship, cerebrovascular (ischemic) stroke. Experimental studies with experimental rodent models and cultures (cardiac myocytes, endothelial cells) indicate that moderate …

Gastrocnemius-Soleus Muscle Tendon Unit Changes Over The First 12 Weeks Of Adjusted Age In Infants Born Preterm, Marybeth Grant-Beuttler, Robert J. Palisano, Debra P. Miller, Barbara Reddien Wagner, Carolyn B. Heriza, Patricia A. Shewokis

Physical Therapy Faculty Articles and Research

Background and Purpose: Differences in the gastrocnemius-soleus muscle and tendon have been documented shortly after birth in infants born preterm compared with infants born at term. Knowledge of muscle tendon unit lengths at term age to 12 weeks of age in infants born preterm may be useful in understanding motor development.

Participants and Method: Gastrocnemius-soleus muscle tendon unit lengths were compared at term age, at 6 weeks of age, and at 12 weeks of age (preterm adjusted age) in 20 infants born full term and 22 infants born preterm.

Results: Significant differences were found between the 2 groups on taut …

Multimodality Education For Airway Endoscopy Skill Development., Ellen S. Deutsch, Thomas Christenson, Joseph Curry, Jobayer Hossain, Karen Zur, Ian Jacobs

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES: Airway endoscopy is a difficult skill to master. A unique practicum was designed to help otolaryngology residents develop endoscopy skills. The learning modalities included lectures, an animal laboratory, high-fidelity manikins, virtual bronchoscopy simulation, and standardized patients. This study compares the relative subjective value of these learning modalities for skill development and realism. METHODS: Participants used a Likert scale (1=disagree to 5=agree) and open responses to anonymously rate the efficacy of 5 learning modalities for teaching airway management, endoscopy skills, and clinical leadership and for providing a realistic experience. RESULTS: The results in 2007 were uniformly positive, with mean scores …

Enhanced Estrogen-Induced Proliferation In Obese Rat Endometrium, Qian Zhang, Qi Shen, Joseph Celestino, Michael R Milam, Shannon N Westin, Robin A Lacour, Larissa A Meyer, Gregory L Shipley, Peter J A Davies, Lei Deng, Adrienne S Mccampbell, Russell R Broaddus, Karen H Lu

Faculty, Staff and Student Publications

OBJECTIVE: We tested the hypothesis that the proliferative estrogen effect on the endometrium is enhanced in obese vs lean animals.

STUDY DESIGN: Using Zucker fa/fa obese rats and lean control, we examined endometrial cell proliferation and the expression patterns of certain estrogen-regulated proproliferative and antiproliferative genes after short-term treatment with estradiol.

RESULTS: No significant morphologic/histologic difference was seen between the obese rats and the lean rats. Estrogen-induced proproliferative genes cyclin A and c-Myc messenger RNA expression were significantly higher in the endometrium of obese rats compared with those of the lean control. Expression of the antiproliferative gene p27Kip1 was suppressed …

Author Response To Invited Commentary By Heathcock [Commentary For: Gastrocnemius/Soleus Muscle Tendon Unit Changes Over The First 12 Weeks Of Adjusted Age In Infants Born Preterm], Marybeth Grant-Beuttler, Robert J. Palisano, Debra P. Miller, Barbara Reddien Wagner, Carolyn B. Heriza, Patricia A. Shewokis

Physical Therapy Faculty Articles and Research

"We thank Heathcock for taking the time to write her commentaryregarding our study. Her comments are interesting, and our subsequent investigation into these ideas has led us to uncover some enlightening evidence in relation to the topics raised in the commentary. We will attempt to review each of the topics raised and the evidence associated with these topics."

The Role Of Nf-Κb In Pparα-Mediated Hepatocarcinogenesis, Howard P. Glauert, Karen Calfee-Mason, Yixin Li, Vani Nilakantan, Michelle L. Twaroski, Job Tharappel, Brett T. Spear

Graduate Center for Nutritional Sciences Faculty Publications

In this review, the role of NF-kappaB in the induction of hepatocarcinogenesis by peroxisome proliferators is examined. The administration of peroxisome proliferators for more than a three-day period leads to the activation of NF-kappaB in the livers of rats and mice. On the other hand, peroxisome proliferator activated receptor-alpha (PPARalpha) activation in non-hepatic tissues can lead to the inhibition of NF-kappaB activation. Several lines of evidence support the hypothesis that the activation of NF-kappaB by peroxisome proliferators in the liver is mediated by oxidative stress. The role of NF-kappaB in peroxisome proliferator-induced hepatocarcinogenesis has been examined using NF-kappaB knockout models. …

Mitostatin, A Putative Tumor Suppressor On Chromosome 12q24.1, Is Downregulated In Human Bladder And Breast Cancer., A Vecchione, M Fassan, V Anesti, A Morrione, S Goldoni, G Baldassarre, D Byrne, D D'Arca, J P Palazzo, J Lloyd, L Scorrano, L G Gomella, R V Iozzo, R Baffa

Department of Urology Faculty Papers

Allelic deletions on human chromosome 12q24 are frequently reported in a variety of malignant neoplasms, indicating the presence of a tumor suppressor gene(s) in this chromosomal region. However, no reasonable candidate has been identified so far. In this study, we report the cloning and functional characterization of a novel mitochondrial protein with tumor suppressor activity, henceforth designated MITOSTATIN. Human MITOSTATIN was found within a 3.2-kb transcript, which encoded a approximately 62 kDa, ubiquitously expressed protein with little homology to any known protein. We found homozygous deletions and mutations of MITOSTATIN gene in approximately 5 and approximately 11% of various cancer-derived …

Com Outlook Winter 2009, College Of Osteopathic Medicine

COM Outlook

No abstract provided.

Loss Of Ski Expression In Testicular Cancer Leads To An Enhanced Invasive Phenotype Through Both Bmp-Dependent And Bmp-Independent Pathways, Amy N. Nash

Theses, Dissertations and Capstones

The proto-oncogene SKI is a transcription factor and a co-repressor of the TGFβ superfamily, including TGF

β and BMP. However, additional data suggests that SKI may function as a tumor suppressor in some cell types. The TGFβ superfamily has been implicated in cancer progression and germ cell migration. Testicular cancer afflicts men during their peak reproductive years and is the most common cancer among men of this age group. Cisplatin-based chemotherapy is the standard treatment for testicular cancer. This treatment can lead to undesirable side effects, including infertility. We have shown that SKI expression is decreased in testicular germ cell …

No Effect Of Prenatal Alcohol Exposure On Activity In Three Inbred Strains Of Mice, Chris Downing, Christina Balderrama-Durbin, Jonathan Hayes, Thomas E. Johnson, David Gilliam

SPS Faculty Publications

Aims: Prenatal exposure to alcohol can have adverse effects on the developing fetus. Two of the hallmarks of children exposed to alcohol prenatally are attention deficits and hyperactivity. While hyperactivity has been observed in rats following prenatal ethanol exposure, few studies have examined these effects in mice. The present study investigated the effects of prenatal ethanol exposure on activity in mice from three inbred strains: C57BL/6 (B6), Inbred Long Sleep (ILS) and Inbred Short Sleep (ISS).

Methods: On days 7 through 18 of gestation, mice were intragastrically intubated twice daily with either 3.0 g/kg Ethanol (E) or an isocaloric amount …

Apd2: The Updated Antimicrobial Peptide Database And Its Application In Peptide Design., Guangshun Wang, Xia Li, Zhe Wang

Journal Articles: Pathology and Microbiology

The antimicrobial peptide database (APD, http://aps.unmc.edu/AP/main.php) has been updated and expanded. It now hosts 1228 entries with 65 anticancer, 76 antiviral (53 anti-HIV), 327 antifungal and 944 antibacterial peptides. The second version of our database (APD2) allows users to search peptide families (e.g. bacteriocins, cyclotides, or defensins), peptide sources (e.g. fish, frogs or chicken), post-translationally modified peptides (e.g. amidation, oxidation, lipidation, glycosylation or d-amino acids), and peptide binding targets (e.g. membranes, proteins, DNA/RNA, LPS or sugars). Statistical analyses reveal that the frequently used amino acid residues (>10%) are Ala and Gly in bacterial peptides, Cys and Gly in plant …

Sildenafil For The Treatment Of Pulmonary Hypertension In Pediatric Patients, Alice J. Huddleston, Chad A. Knoderer, Jennifer L. Morris, Eric S. Ebenroth

Scholarship and Professional Work – COPHS

Sildenafil is a phosphodiesterase 5 inhibitor widely used for the treatment of pulmonary hypertension in children. Despite limited available safety and efficacy evidence, use of sildenafil continues to increase. To date, sildenafil use for pediatric pulmonary hypertension has been characterized for 193 children through 16 studies and 28 case series and reports. The primary efficacy data suggest that sildenafil is beneficial for facilitating the weaning of inhaled nitric oxide in children after cardiac surgery. Compiled safety data suggest that sildenafil is well tolerated among children with idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease. This …

Ua94/6/1 Student / Alumni Personal Papers Western Kentucky University Small Collections, Wku Archives

WKU Archives Collection Inventories

Small collections of personal papers and oral histories relating to the Western Kentucky University.

Snai1 And Snai2 Are Asymmetrically Expressed At The 2-Cell Stage And Become Segregated To The Te In The Mouse Blastocyst., Christine E Bell, Andrew J Watson

Obstetrics & Gynaecology Publications

SNAI1 and SNAI2 are transcription factors that initiate Epithelial-to-Mesenchymal cell transitions throughout development and in cancer metastasis. Here we show novel expression of SNAI1 and SNAI2 throughout mouse preimplantation development revealing asymmetrical localization of both SNAI1 and SNAI2 in individual blastomeres beginning at the 2-cell stage through to the 8-cell stage where SNAI1 and SNAI2 are then only detected in outer cells and not inner cells of the blastocyst. This study implicates SNAI1 and SNAI2 in the lineage segregation of the trophectoderm and inner cell mass, and provides new insight into these oncogenes.

Trichostatin A Inhibits Corneal Haze In Vitro And In Vivo, Ajay Sharma, Maneesh M. Mehan, Sunilima Sinha, John W. Cowden, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. Trichostatin A (TSA), a histone deacetylase inhibitor, has been shown to suppress TGF- –induced fibrogenesis in many nonocular tissues. The authors evaluated TSA cytotoxicity and its antifibrogenic activity on TGF- –driven fibrosis in the cornea with the use of in vitro and in vivo models.

METHODS. Human corneal fibroblasts (HSFs) were used for in vitro studies, and New Zealand White rabbits were used for in vivo studies. Haze in the rabbit cornea was produced with photorefractive keratectomy (PRK) using excimer laser. Trypan blue exclusion and MTT assays evaluated TSA cytotoxicity to the cornea. Density of haze in the rabbit …

X4 Human Immunodeficiency Virus Type 1 Gp120 Down-Modulates Expression And Immunogenicity Of Codelivered Antigens, Avi-Hai Hovav, Michael Santosuosso, Maytal Bivas-Benita, Andre Plair, Alex Cheng, Mazal Elnekave, Elda Righi, Tao Chen, Satoshi Kashiwagi, Michael W. Panas, Shi-Hua Xiang, Karina Furmanov, Norman L. Letvin, Mark C. Poznansky

Nebraska Center for Virology: Faculty Publications

In order to increase the immune breadth of human immunodeficiency virus (HIV) vaccines, strategies such

as immunization with several HIV antigens or centralized immunogens have been examined. HIV-1 gp120

protein is a major immunogen of HIV and has been routinely considered for inclusion in both present and

future AIDS vaccines. However, recent studies proposed that gp120 interferes with the generation of immune

response to codelivered antigens. Here, we investigate whether coimmunization with plasmid-encoded gp120

alters the immune response to other coadministered plasmid encoded antigens such as luciferase or ovalbumin

in a mouse model. We found that the presence of gp120 …

Comparison Of Replication-Competent, First Generation, And Helper-Dependent Adenoviral Vaccines, Eric A. Weaver, Pramod N. Nehete, Stephanie S. Buchl, Julien S. Senac, Donna Palmer, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

All studies using human serotype 5 Adenovirus (Ad) vectors must address two major obstacles: safety and the presence of pre-existing neutralizing antibodies. Helper-Dependent (HD) Ads have been proposed as alternative vectors for gene therapy and vaccine development because they have an improved safety profile. To evaluate the potential of HD-Ad vaccines, we compared replication-competent (RC), first-generation (FG) and HD vectors for their ability to induce immune responses in mice. We show that RC-Ad5 and HD-Ad5 vectors generate stronger immune responses than FG-Ad5 vectors. HD-Ad5 vectors gave lower side effects than RC or FG-Ad, producing lower levels of tissue damage and …

Genetic And Hormonal Factors Modulate Spreading Depression And Transient Hemiparesis In Mouse Models Of Familial Hemiplegic Migraine Type 1, Katharina Eikermann-Haerter, Ergin Dileköz, Chiho Kudo, Sean I Savitz, Christian Waeber, Michael J Baum, Michel D Ferrari, Arn M J M Van Den Maagdenberg, Michael A Moskowitz, Cenk Ayata

Faculty, Staff and Student Publications

Familial hemiplegic migraine type 1 (FHM1) is an autosomal dominant subtype of migraine with aura that is associated with hemiparesis. As with other types of migraine, it affects women more frequently than men. FHM1 is caused by mutations in the CACNA1A gene, which encodes the alpha1A subunit of Cav2.1 channels; the R192Q mutation in CACNA1A causes a mild form of FHM1, whereas the S218L mutation causes a severe, often lethal phenotype. Spreading depression (SD), a slowly propagating neuronal and glial cell depolarization that leads to depression of neuronal activity, is the most likely cause of migraine aura. Here, we have …

Smoking And Second Hand Smoking In Adolescents With Chronic Kidney Disease: A Report From The Chronic Kidney Disease In Children (Ckid) Cohort Study, Abiodun Aderogba Omoloja, J. Jerry-Fluker, Alison Abraham, S. Furth, B. Warady, M. Mitsnefes

Pediatrics Faculty Publications

The goal of this study was to determine the prevalence of smoking and second hand smoking [SHS] in adolescents with CKD and their relationship to baseline parameters at enrollment in the CKiD, observational cohort study of 600 children (aged 1-16 yrs) with Schwartz estimated GFR of 30-90 ml/min/1.73m2. 239 adolescents had self-report survey data on smoking and SHS exposure: 21 [9%] subjects had “ever” smoked a cigarette. Among them, 4 were current and 17 were former smokers. Hypertension was more prevalent in those that had “ever” smoked a cigarette (42%) compared to non-smokers (9%), p

A New Pulsed Electric Field Therapy For Melanoma Disrupts The Tumor's Blood Supply And Causes Complete Remission Without Recurrence, Richard Nuccitelli, Xinhua Chen, Andrei G. Pakhomov, Wallace H. Baldwin, Saleh Sheikh, Jennifer L. Pomicter, Wei Ren, Chris Osgood, R. James Swanson, Juergen F. Kolb, Stephen J. Beebe, Karl H. Schoenbach

Bioelectrics Publications

We have discovered a new, ultrafast therapy for treating skin cancer that is extremely effective with a total electric field exposure time of only 180 mu sec. The application of 300 high-voltage (40 kV/cm), ultrashort (300 nsec) electrical pulses to murine melanomas in vivo triggers both necrosis and apoptosis, resulting in complete tumor remission within an average of 47 days in the 17 animals treated. None of these melanomas recurred during a 4-month period after the initial melanoma had disappeared. These pulses generate small, long-lasting, rectifying nanopores in the plasma membrane of exposed cells, resulting in increased membrane permeability to …

Osteoarthritis Associated With Estrogen Deficiency., Jorge A Roman-Blas, Santos Castañeda, Raquel Largo, Gabriel Herrero-Beaumont

Jefferson Institute of Molecular Medicine Papers and Presentations

Osteoarthritis (OA) affects all articular tissues and finally leads to joint failure. Although articular tissues have long been considered unresponsive to estrogens or their deficiency, there is now increasing evidence that estrogens influence the activity of joint tissues through complex molecular pathways that act at multiple levels. Indeed, we are only just beginning to understand the effects of estrogen deficiency on articular tissues during OA development and progression, as well as on the association between OA and osteoporosis. Estrogen replacement therapy and current selective estrogen receptor modulators have mixed effectiveness in preserving and/or restoring joint tissue in OA. Thus, a …

An Mdm2 Antagonist (Mi-319) Restores P53 Functions And Increases The Life Span Of Orally Treated Follicular Lymphoma Bearing Animals, Ramzi M. Mohammad, Jack Wu, Asfar S. Azmi, Amro Aboukameel, Angela Sosin, Sherwin Wu, Dajun Yang, Shaomeng Wang, Ayad M. Al-Katib

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

MI-319 is a synthetic small molecule designed to target the MDM2-P53 interaction. It is closely related to MDM2 antagonists MI-219 and Nutlin-3 in terms of the expected working mechanisms. The purpose of this study was to evaluate anti-lymphoma activity of MI-319 in WSU-FSCCL, a B-cell follicular lymphoma line. For comparison purpose, MI-319, MI-219 and Nutlin-3 were assessed side by side against FSCCL and three other B-cell hematological tumor cell lines in growth inhibition and gene expression profiling experiments.

Results

MI-319 was shown to bind to MDM2 protein with an affinity slightly higher than that of MI-219 and Nutlin-3. …

New Targets For The Treatment Of Follicular Lymphoma, Nishant Tageja, Subhash Padheye, Prasad Dandawate, Ayad Al-Katib, Ramzi M. Mohammad

Wayne State University Associated BioMed Central Scholarship

Abstract

The last two decades have witnessed striking advances in our understanding of the biological factors underlying the development of Follicular lymphoma (FL). Development of newer treatment approaches have improved the outlook for many individuals with these disorders; however, with these advances come new questions. Given the long-term survival of patients with FL, drugs with favourable side-effect profile and minimal long-term risks are desired. FL is incurable with current treatment modalities. It often runs an indolent course with multiple relapses and progressively shorter intervals of remission. The identification of new targets and development of novel targeted therapies is imperative to …

Calpain Inhibition Attenuates Inflammatory And Neurodegenerative Events In Animal Models Of Multiple Sclerosis, Mary Kelly Guyton

MUSC Theses and Dissertations

Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system (CNS) that affects approximately 400,000 people in the United States every year and results in fatigue, visual dysfunction, and paralysis. Inflammatory events associated with MS include activation of auto-reactive T cells and migration of these and other immune cells into the CNS, leading to production of cytokines and other mediators and to demyelination. Astrogliosis and microgliosis are also prominent inflammatory features of MS. Neurodegenerative events such as axonal damage and loss of neurons and oligodendrocytes also contribute to clinical disease symptoms. Cell death is thought to occur, …

Influencing T Helper Cell Bias In Autoimmunity, Jonathan Ty Butler

MUSC Theses and Dissertations

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that affects approximately 400,000 people in the United States every year and results in neurological deficits. Inflammatory events associated with MS include activation of auto-reactive T cells and migration of these and other immune cells into the CNS, leading to a coordinated attack upon oligodendrocytes and demyelination. Most current therapies only treat the symptoms of disease, not the cause, which is still in large part unknown. Therefore, the identification of the etiology of this complex disease and the development of new therapies is of great importance. Targeting …

Treatment Options For Neuropathic Pain, Sara Akre

Honors Program Theses

Neuropathic pain is caused by injury to or disease of the nervous system. It affects many people around the world and is a symptom of several diseases. In the United States, it is estimated that up to 3% of Americans have neuropathic pain, which costs the healthcare system $40 billion annually (Gilron et al. 2006). It is, unfortunately, difficult to ameliorate or eliminate due to the complexity of the nervous system and its plasticity and is, therefore, a chronic condition. Health care professionals continually struggle to treat patients' pain and, since tolerance to painkillers is easily built up, this often …

Transfusion Related Acute Lung Injury--Trali: An Under Diagnosed Entity, Bushra Moiz, Hasanat Sharif, Fauzia Ahmad Bawany

Department of Pathology and Laboratory Medicine

Transfusion related acute lung injury (TRALI) is a life-threatening complication of transfusion of blood and its components resembling acute respiratory distress syndrome (ARDS) or acute lung injury (ALI). TRALI is a particular form of ARDS that follows blood transfusion and is caused by donor-derived antibodies present in the transfused products, reacting with the recipients' blood cells, inducing release of inflammatory mediators thus compromising lung functions. Anti-HLA antibodies are the most frequently indicted inducers in this category. Literature search has not revealed any documented case of TRALI from Pakistan. This in no way implies that TRALI is non existent in this …