Digital Commons Network^™

Vorinostat: A Potent Agent To Prevent And Treat Laser-Induced Corneal Haze, Ashish Tandon, Jonathan C. K. Tovey, Michael R. Waggoner, Ajay Sharma, John W. Cowden, Daniel J. Gibson, Yuanjing Liu, Gregory S. Schultz, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE—This study investigated the efficacy and safety of vorinostat, a deacetylase (HDAC) inhibitor, in the treatment of laser-induced corneal haze following photorefractive keratectomy (PRK) in rabbits in vivo and transforming growth factor beta 1 (TGFβ1) -induced corneal fibrosis in vitro.

METHODS—Corneal haze in rabbits was produced with −9.00 diopters (D) PRK. Fibrosis in cultured human and rabbit corneal fibroblasts was activated with TGFβ1. Vorinostat (25 μm) was topically applied once for 5 minutes on rabbit cornea immediately after PRK for in vivo studies. Vorinostat (0 to 25 μm) was given to human/rabbit corneal fibroblasts for 5 minutes or 48 …

4-Aryl-4h-Naphthopyrans Derivatives: One-Pot Synthesis, Evaluation Of Src Kinase Inhibitory And Anti-Proliferative Activities, Ali Rafinejad, Asal Fallah-Tafti, Rakesh Tiwari, Amir Nasrolahi Shirazi, Dindyal Mandal, Abbas Shafiee, Keykavous Parang, Alireza Foroumadi, Tahmineh Akbarzadeh

Pharmacy Faculty Articles and Research

Background: A series of 2-amino-4-aryl-4H-benzo[h or f]chromene-3-carbonitrile derivatives were synthesized and evaluated for inhibition of Src kinase and cell proliferation in breast carcinoma (BT-20) cell lines.

Methods: The one-pot, three-component reaction of a or beta-naphthol, malonitrile and an aromatic aldehyde in the presence of diammonium hydrogen phosphate was afforded the corresponding 2-amino-4-aryl-4H-benzo[h or f]chromene-3-carbonitrile derivatives, All target compounds were evaluated for inhibition of Src kinase and cell proliferation in breast carcinoma (BT-20) cell lines.

Results: Among all tested compounds, unsubstituted 4-phenyl analog 4a showed Src kinas inhibitory effect with IC50 value of 28.1 mu M and was …

Sexually Transmitted Diseases (Stds), Donald E. Greydanus, Jane Seyler, Hatim A. Omar

Pediatrics Faculty Publications

High rates of unprotected sexual behavior in adolescents result in millions of cases of STDs in the world. This chapter reviews factors inducing high STD rates, specific STDs, and their management based on 2010 U.S. Centers for Disease Control and Prevention (CDC) STD guidelines. Clinicians should screen all their sexually active adolescent patients for STDs and provide preventive education as well as treatment measures.

Association Of Ireb2 And Chrna3 Polymorphisms With Airflow Obstruction In Severe Alpha-1 Antitrypsin Deficiency., Woo Jin Kim, Alice M. Wood, Alan F. Barker, Mark L. Brantly, Edward J. Campbell, Edward Eden, Gerard Mcelvaney, Stephen I. Rennard, Robert A. Sandhaus, James M. Stocks, James K. Stoller, Charlie Strange, Gerard Turino, Edwin K. Silverman, Robert A. Stockley, Dawn L. Demeo

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: The development of COPD in subjects with alpha-1 antitrypsin (AAT) deficiency is likely to be influenced by modifier genes. Genome-wide association studies and integrative genomics approaches in COPD have demonstrated significant associations with SNPs in the chromosome 15q region that includes CHRNA3 (cholinergic nicotine receptor alpha3) and IREB2 (iron regulatory binding protein 2).We investigated whether SNPs in the chromosome 15q region would be modifiers for lung function and COPD in AAT deficiency.

METHODS: The current analysis included 378 PIZZ subjects in the AAT Genetic Modifiers Study and a replication cohort of 458 subjects from the UK AAT Deficiency National …

Triticum Mosaic Poacevirus Enlists P1 Rather Than Hc-Pro To Suppress Rna Silencing-Mediated Host Defense, Satyanarayana Tatineni, Feng Qu, Ruhui Li, Thomas Jack Morris, Roy French

Nebraska Center for Virology: Faculty Publications

Triticum mosaic virus (TriMV) is the type species of the newly established Poacevirus genus in the family Potyviridae. In this study, we demonstrate that in contrast to the helper component- proteinase (HC-Pro) of Potyvirus species, the P1 proteins of TriMV and Sugarcane steak mosaic poacevirus function in suppression of RNA silencing (SRS). TriMV P1 effectively suppressed silencing induced by single- or double-stranded RNAs (ss/ds RNAs), and disrupted the systemic spread of silencing signals at a step after silencing signal production. Interestingly, contrary to enhanced SRS activity of potyviral HC-Pro by co-expression with P1, the presence of TriMV HC-Pro reduced …

Identification Of Molecular Determinants From Moloney Leukemia Virus 10 Homolog (Mov10) Protein For Virion Packaging And Anti-Hiv-1 Activity, Aierken Abudu, Xiaojun Wang, Ying Dang, Tao Zhou, Shi-Hua Xiang, Yong -Hui Zheng

Nebraska Center for Virology: Faculty Publications

Background: MOV₁₀ inhibits HIV-1 replication after being packaged.

Results: A Gag binding plus all but one of seven helicase domains are required for MOV^₁₀ packaging. Nearly all residues are required for anti-HIV-1 activity. Conclusion: Gag binding is not sufficient for MOV₁₀ packaging, and multiple discontinuous domains regulate MOV₁₀ activity.

Significance: These findings uncover a new packaging mechanism and provide new insights into MOV₁₀ antiviral activity.

Primary Uterine Cervix Schwannoma: A Case Report And Review Of The Literature, Maryam Tahmasbi, Johnny Nguyen, Masoumeh Ghayouri, Yuan Shan, Ardeshir Hakam

Pathology and Cell Biology Faculty Publications

Schwannoma (neurilemmoma) is a benign peripheral nerve sheath tumor that occurs in a wide variety of locations; however, its finding in the uterine cervix is extremely rare. We report a case of an incidental primary benign cervical schwannoma in a 48-year-old woman. In the English literature, a few cases of primary schwannoma of the cervix have been reported, which include seven cases of primary malignant cervical schwannoma and only two that are benign. These cases are reviewed in the following discussion.

Attitudes, Beliefs, And Practices Of Providers And Key Opinion Leaders On Emergency Contraception In India, M.E. Khan, Deepthi S. Varma, Isha Bhatnagar, Anvita Dixit, Martha Brady

Reproductive Health

The Population Council undertook this study to assess the knowledge, attitudes, and practices regarding emergency contraception (ECP) among providers in public and private facilities and pharmacies in India. The objectives of the study were to: assess providers' knowledge of ECP's biological mechanism; understand providers' knowledge and attitudes about ECP's safety, effectiveness, and availability as an OTC drug; and identify providers' definitions of “repeated use” and profiling women who are “repeated users” of ECP. This study's findings show that most providers, including doctors and some KOLs, were incorrectly informed about ECP's mechanism of action. Service guidelines are necessary for accurate and …

Receptor Antagonism And Dyskinesia In Parkinson’S Disease, Micaela Morelli, Fabio Blandini, Nicola Simola, Robert A. Hauser

Neurology Faculty Publications

Dyskinesia, a major complication of treatment of Parkinson’s disease (PD), involves two phases: induction, which is responsible for dyskinesia onset, and expression, which underlies its clinical manifestation. The unique cellular and regional distribution of adenosine receptors in basal ganglia areas that are richly innervated by dopamine, and their antagonistic role towards dopamine receptor stimulation, have positioned receptor antagonists as an attractive nondopaminergic target to improve the motor deficits that characterize PD. In this paper, we describe the biochemical characteristics of receptors and the effects of adenosine antagonists in rodent and primate models of PD on L-DOPA-induced dyskinesia, together with relevant …

Treatment Choices Based On Oncotypedx In The Breast Oncology Care Setting, Teri L. Malo, Isaac Lipkus, Tobi Wilson, Hyo S. Han, Geza Acs, Susan T. Vadaparampil

Pathology and Cell Biology Faculty Publications

Introduction. This study aimed to evaluate whether OncotypeDx test results predict receipt of adjuvant chemotherapy in breast cancer patients who received an OncotypeDx recurrence score (RS). Materials and Methods. Pathology records were used to identify breast cancer patients who had OncotypeDx testing between December 2004 and January 2009 (𝑛 = 1 1 8). Patient sociodemographic information, tumor characteristics, RS, and treatment-specific data were collected via chart review. RS was classified as follows: low (R S ≤ 1 7), intermediate (RS = 18–30), or high (R S ≥ 3 1). Bivariate analyses were …

Peripheral Nerve Repair With Cultured Schwann Cells: Getting Closer To The Clinics, Maria Carolina O. Rodrigues, Antonio Antunes Rodrigues, Loren E. Glover, Julio Voltarelli, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Peripheral nerve injuries are a frequent and disabling condition, which affects 13 to 23 per 100.000 persons each year. Severe cases, with structural disruption of the nerve, are associated with poor functional recovery. The experimental treatment using nerve grafts to replace damaged or shortened axons is limited by technical difficulties, invasiveness, and mediocre results. Other therapeutic choices include the adjunctive application of cultured Schwann cells and nerve conduits to guide axonal growth. The bone marrow is a rich source of mesenchymal cells, which can be differentiated in vitro into Schwann cells and subsequently engrafted into the damaged nerve. Alternatively, undifferentiated …

Development And Characterization Of Anti-Nitr9 Antibodies, Radhika N. Shah, Ivan Rodriguez-Nunez, Donna D. Eason, Robert N. Haire, Julien Y. Bertrand, Valērie Wittamer, David Traver, Shila K. Nordone

Pediatrics Faculty Publications

The novel immune-type receptors (NITRs), which have been described in numerous bony fish species, are encoded by multigene families of inhibitory and activating receptors and are predicted to be functional orthologs to the mammalian natural killer cell receptors (NKRs). Within the zebrafish NITR family, nitr9 is the only gene predicted to encode an activating receptor. However, alternative RNA splicing generates three distinct nitr9 transcripts, each of which encodes a different isoform. Although nitr9 transcripts have been detected in zebrafish lymphocytes, the specific hematopoietic lineage(s) that expresses Nitr9 remains to be determined. In an effort to better understand the role of …

Advancing Our Understanding Of The Inheritance And Transmission Of Pectus Excavatum, Lisa Horth, Michael W. Stacey, Virginia K. Proud, Kara Segna, Chelsea Rutherford, Donald Nuss, Robert E. Kelly

Bioelectrics Publications

Pectus excavatum is the most common congenital chest wall abnormality expressed in children, yet its inheritance is poorly understood. Here we present the first comprehensive assessment of the inheritance of this disorder. After evaluating 48 pedigrees and 56 clinical traits of probands and family members, we find strong evidence of autosomal recessive, genetic control for this disorder. Additionally there is likely more than one pectus disease-associated allele, as well as a relatively large number of disease allele carriers in the human population. Some clinical traits appear important and may serve as reliable indicators for predicting the likelihood of pectus excavatum …

Research Annual Report 2012, Children's Mercy Hospital

Research Annual Reports

Annual report of the research at Children's Mercy Hospital in Kansas City MO, a pediatric medical center.

5q Minus Myelodysplasia Associated With Multiple Epithelioid Granulomas Within Conventional Renal Cell Carcinoma, Rahul G. Matnani, Roshan K Patel, Stephen E Strup, Rouzan Karabakhtsian

Pathology and Laboratory Medicine Faculty Publications

A 69-year-old Caucasian female, with a previous diagnosis of 5q minus myelodysplastic syndrome, presented with conventional renal cell carcinoma (RCC) associated with multiple-epithelioid nonnecrotizing granulomas. Two previous reports of sarcoidosis, primarily involving the lung and skin, have been described in patients with 5q minus myelodysplasia. A cluster of closely linked genes encoding for cytokines such as IL-4, IL-5, and IL-3 are present on chromosome 5q. Hence, in sarcoidosis, cytokine imbalances associated with the deletion of these cytokine genes have been postulated. However, an occurrence of epithelioid granulomas within a carcinoma, in preexisting clonal myelodysplastic syndrome, has not been described. The …

Gene Therapy In The Cornea: 2005--Present, Rajiv R. Mohan, Jonathan C. K. Tovey, Ajay Sharma, Ashish Tandon

Pharmacy Faculty Articles and Research

Successful restoration of vision in human patients with gene therapy affirmed its promise to cure ocular diseases and disorders. The efficacy of gene therapy is contingent upon vector and mode of therapeutic DNA introduction into targeted cells/tissues. The cornea is an ideal tissue for gene therapy due to its ease of access and relative immune-privilege. Considerable progress has been made in the field of corneal gene therapy in last 5 years. Several new gene transfer vectors, techniques and approaches have evolved. Although corneal gene therapy is still in its early stages of development, the potential of gene-based interventions to treat …

Sleep Strategies: Sleep In Women A Changing Perspective, Misha Peter, Md, Ritu G. Grewal, Md

Jefferson Sleep Disorders Center in the News

As with many other specialties, sleep medicine has been shifting toward helping clinicians obtain a better understanding of gender-specific issues in disorders and disturbances. It is easier today to appreciate the complex dynamics of biological, psychosocial, and cultural factors that define sleep patterns and problems in women. Sleep in women changes across their life spans, with three major shifts likely due to hormonal differences: at the onset of the menstrual cycle, during pregnancy, and during the perimenopausal period.

Homeostatic Imbalance In Epithelial Ducts And Its Role In Carcinogenesis, Katarzyna A. Rejniak

Oncologic Sciences Faculty Publications

An epithelial duct is a well-defined multicellular structure composed of tightly packed cells separating and protecting body compartments that are used for enzyme secretion and its transport across the internal. The structural and functional integrity (homeostasis) of such ducts is vital in carrying many life functions (breathing, lactation, production of hormones). However, the processes involved in maintaining the homeostatic balance are not yet fully understood. On the other hand, the loss of epithelial tissue architecture, such as filled lumens or ductal disorganization, are among the first symptoms of the emerging epithelial tumors (carcinomas). Using the previously developed biomechanical model of …

Influence Of Perceived Racial Discrimination On Health And Behaviour Of Immigrant Children In British Columbia, Anne George, Cherylynn Bassani, Robert Armstrong

Paediatrics and Child Health, East Africa

This study examines the influence of perceived discrimination on the health and behaviour of ethnic minority immigrant children in British Columbia, Canada. Using data from the New Canadian Children and Youth Study, we examine perceived discrimination experienced by the parent, family, and cultural group in Canada to test the influence of micro-, meso-, and macrolevels of discrimination on children. Families from 6 ethnic backgrounds participated in the study. Parents’ perceptions of the child’s health and six behavioral scales (hyperactivity, prosocial behaviour, emotional problems, aggression, indirect aggression, and a general combined behaviour scale) were examined as outcome variables. After controlling for …

Comprehensive Analysis Of Common Serum Liver Enzymes As Prospective Predictors Of Hepatocellular Carcinoma In Hbv Patients., Hie-Won Hann, Shaogui Wan, Ronald E Myers, Richard S Hann, Jinliang Xing, Bicui Chen, Hushan Yang

Department of Medicine Faculty Papers

BACKGROUND: Serum liver enzymes are frequently tested in clinics to aid disease diagnosis. Large observational studies indicated that these enzymes might predict cancer risk and mortality. However, no prospective study has reported on their relationships with the risk of HBV-related hepatocellular carcinoma (HCC). METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the predictive values of four routinely tested liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and gamma-glutamyltransferase [GGT]) in HCC risk in a prospectively enrolled clinical cohort of 588 Korean American HBV patients. For all four enzymes, the baseline level as well as the average and maximum levels during the …

Modulation Of Anti-Tumor Immune Response By Tgf-Β-Inducible Early Gene 1 (Tieg1), Andi Cani

Wayne State University Theses

Cancer immunotherapy has had limited clinical efficacy partly because regulatory T cells (Treg) suppress the immune response to tumor-associated antigens. Inducible regulatory T cells (iTreg), which are converted from naïve CD4 T cells by TGF-β, an abundant cytokine in the tumor microenvironment, may contribute to this immune suppression. Induction of Foxp3 by TGF-β is mediated by the transcription factor TIEG1 and abrogation of this protein prevents Foxp3 expression. We are testing the hypothesis that blockade of TIEG1 to prevent iTreg conversion will enhance immune response in DNA vaccination to the tumor associated antigen Her-2. Wild type and TIEG1 knockout mice …

Neuroangiogenesis: A Vascular Basis For Alzheimer's Disease And Cognitive Decline During Aging, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Angiogenesis directs development of the brain's microcirculation during antenatal and postnatal development, but its role later in life is less well recognized. I contend that during senescence a reduced cerebral capillary density accounts in part for the vascular cognitive impairment observed in many older persons and possibly for some forms of Alzheimer's disease. I propose that neuroangiogenesis is essential throughout adult life for maintaining the microcirculation of the cerebral cortex and elsewhere in the brain and that it commonly declines with old age. To support this hypothesis I have examined the neurological literature for relevant studies on cerebral capillary density …

Bcr-Abl-Mediated Regulation Of Sphingomyelin Synthase, Tara Ann Burns

MUSC Theses and Dissertations

SMS is an enzyme belonging to the sphingolipid metabolic pathway. Since the discovery and initial characterizations of sphingolipids (SLs) in 1884, extensive research has established that these molecules not only are structural components of eukaryotic membranes but they are also critical bioactive lipids involved in fundamental cellular processes such as proliferation, differentiation, apoptosis, inflammation, migration, and autophagy. In particular, SMS produces sphingomyelin (SM) in mammalian cells by transfering the phosphorylcholine moiety from phosphatidylcholine (PC) onto ceramide forming SM and diacylglycerol (DAG). Both ceramide and DAG are bioactive lipids with opposing functions, and SMS produces sphingomyelin (SM) while consuming ceramide (negative …

Dynamics Of Envelope Evolution In Clade C Shiv-Infected Pig-Tailed Macaques During Disease Progression Analyzed By Ultra-Deep Pyrosequencing, For Yue Tso, Damien C. Tully, Sandra Gonzalez, Christopher Quince, On Ho, Patricia Polacino, Ruth M. Ruprecht, Shiu-Lok Hu, Charles Wood

Nebraska Center for Virology: Faculty Publications

Understanding the evolution of the human immunodeficiency virus type 1 (HIV-1) envelope during disease progression can provide tremendous insights for vaccine development, and simian-human immunodeficiency virus (SHIV) infection of nonhuman primate provides an ideal platform for such studies. A newly developed clade C SHIV, SHIV-1157ipd3N4, which was able to infect rhesus macaques, closely resembled primary HIV-1 in transmission and pathogenesis, was used to infect several pig-tailed macaques. One of the infected animals subsequently progressed to AIDS, whereas one remained a nonprogressor. The viral envelope evolution in the infected animals during disease progression was analyzed by a bioinformatics approach using ultra-deep …

The Use Of Preoperative Epoetin-Α In Revision Hip Arthroplasty., Lawrence A Delasotta, Ashwin Rangavajjula, Michael L Frank, Jamie Blair, Fabio Orozco, Alvin Ong

Rothman Institute Papers

PURPOSE: To evaluate the efficacy of preoperative epoetin-α on the revision hip arthroplasty patient. We hypothesized that epoetin-α will reduce blood transfusion. A pertinent review of the literature is provided.

METHODS: Forty-six patients were retrospectively reviewed. Sixteen patients received epoetin-α. Patients were case matched by age, preoperative hemoglobin, surgery, gender, and BMI. The clinical triggers for blood transfusion during or after the procedure were determined based on peri- and postoperative hemoglobin levels, ASA score, and/or clinical symptoms consistent with anemia. Blood salvage was not used.

RESULTS: Blood transfusion and length of stay were decreased in the epoetin-α group. Hemoglobin in …

Vitamin D Mitigates Age-Related Cognitive Decline Through The Modulation Of Pro-Inflammatory State And Decrease In Amyloid Burden, Teresita L. Briones, Hala Darwish

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Increasing evidence shows an association between the use of vitamin D and improvement in age-related cognitive decline. In this study, we investigated the possible mechanisms involved in the neuroprotective effects of vitamin D on age-related brain changes and cognitive function.

Methods

Male F344 rats aged 20 months (old) and 6 months (young) were used and randomly assigned to either vitamin D supplementation or no supplementation (control). A total of n = 39 rats were used in the study. Rats were individually housed and the supplementation group received a subcutaneous injection of vitamin D (1, α25-dihydroxyvitamin D3) 42 I.U./Kg …

Segmentation Of Corpus Callosum Using Diffusion Tensor Imaging: Validation In Patients With Glioblastoma, Mohammad-Reza Nazem-Zadeh, Sona Saksena, Abbas Babajani-Fermi, Quan Jiang, Hamid Soltanian-Zadeh, Mark Rosenblum, Tom Mikkelsen, Rajan Jain

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

This paper presents a three-dimensional (3D) method for segmenting corpus callosum in normal subjects and brain cancer patients with glioblastoma.

Methods

Nineteen patients with histologically confirmed treatment naïve glioblastoma and eleven normal control subjects underwent DTI on a 3T scanner. Based on the information inherent in diffusion tensors, a similarity measure was proposed and used in the proposed algorithm. In this algorithm, diffusion pattern of corpus callosum was used as prior information. Subsequently, corpus callosum was automatically divided into Witelson subdivisions. We simulated the potential rotation of corpus callosum under tumor pressure and studied the reproducibility of the …

Augmented Annotation And Orthologue Analysis For Oryctolagus Cuniculus: Better Bunny, Douglas B. Craig, Sujatha Kannan, Alan A. Dombkowski

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The rabbit is an important model organism used in a wide range of biomedical research. However, the rabbit genome is still sparsely annotated, thus prohibiting extensive functional analysis of gene sets derived from whole-genome experiments. We developed a web-based application that provides augmented annotation and orthologue analysis for rabbit genes. Importantly, the application allows comprehensive functional analysis through the use of orthologous relationships.

Results

Using data extracted from several public bioinformatics repositories we created Better Bunny, a database and query tool that extensively augments the available functional annotation for rabbit genes. Using the complete set of target genes …

Vip And Host Immunity, Xiaoyu Jiang

Wayne State University Dissertations

The purpose of the current dissertation was to examine how VIP regulates host immunity and corneal healing, specifically, its control of growth factors and TLR expression in the P. aeruginosa infected cornea. Firstly, VIP treatment increased growth factor expression (EGF, GHF, FGF and VEGF) in infected cornea. Notably, treatment with a mixture of EGF, FGF and HGF prevented corneal perforation, reduced pro-inflammatory cytokines and bacterial plate count, while increasing anti-inflammatory cytokines and antimicrobials such as murine beta-defensin2 and 3.

We also investigated the expression of TLR-signaling pathways in P. aeruginosa infected corneas with or without VIP treatment. PCR array and …

Endoplasmic Reticulum Calcium-Independent Phospholipase A2 Gamma (Er-Ipla2Γ): Role In Oxidative Stress-Induced Lipid Peroxidation, Ca2+ Release, Phospholipid Homeostasis And Cell Death In The Kidney, Andre Chioke Eaddy

MUSC Theses and Dissertations

Acute kidney injury and chronic kidney disease are becoming more prevalent and have high morbidity and mortality, and despite several therapies targeted towards treating or preventing kidney injury, outcomes have been unchanged for many years. Calcium­independent phospholipase A2y (iPLA2γ) is one of seven Ca2+-independent PLA2 enzymes and represents a potential therapeutic target in kidney disease because of its unique subcellular localization and its potential as the putative membrane remodeling/repair enzyme. Studies in our laboratory suggest iPLA2γ is cytoprotective during oxidant injury by preventing and/or repairing oxidant-induced lipid peroxidation and pointed to ER-iPLA2γ as the major component of membrane repair and …