Digital Commons Network^™

Role Of Transforming Growth Factor Beta In Corneal Function, Biology And Pathology, Ashish Tandon, Jonathan C. K. Tovey, Ajay Sharma, Rangan Gupta, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Transforming growth factor-beta (TGFβ) is a pleiotropic multifunctional cytokine that regulates several essential cellular processes in many parts of the body including the cornea. Three isoforms of TGFβ are known in mammals and the human cornea expresses all of them. TGFβ1 has been shown to play a central role in scar formation in adult corneas whereas TGFβ2 and TGFβ3 have been implicated to play a critical role in corneal development and scarless wound healing during embryogenesis. The biological effects of TGFβ in the cornea have been shown to follow SMAD dependent as well as SMAD-independent signaling pathways depending upon cellular …

Gene Delivery In The Equine Cornea: A Novel Therapeutic Strategy, Dylan G. Buss, Ajay Sharma, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To determine if hybrid adeno-associated virus serotype 2/5 (AAV5) vector can effectively deliver foreign genes into the equine cornea without causing adverse side effects. The aims of this study were to: (i) evaluate efficacy of AAV5 to deliver therapeutic genes into equine corneal fibroblasts (ECFs) using enhanced green fluorescent protein (EGFP) marker gene and (ii) establish the safety of AAV5 vector for equine corneal gene therapy.

Animal Material—Primary ECF cultures were harvested from healthy donor equine corneas. Cultures were maintained at 370C in humidified atmosphere with 5% CO2.

Procedure—AAV5 vector expressing EGFP under control of hybrid cytomegalovirus (CMV) + chicken …

Efficacy And Safety Of Mitomycin C As An Agent To Treat Corneal Scarring In Horses Using An In Vitro Model, Dylan G. Buss, Ajay Sharma, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—Mitomycin C (MMC) is used clinically to treat corneal scarring in human patients. We investigated the safety and efficacy of MMC to treat corneal scarring in horses by examining its effects at the early and late stages of disease using an in-vitro model.

Procedure—An in-vitro model of equine corneal fibroblast (ECF) developed was used. The equine corneal fibroblast or myofibroblast cultures were produced by growing primary ECF in the presence or absence of transforming growth factor beta-1 (TGFβ1) under serum-free conditions. The MMC dose for the equine cornea was defined with dose-dependent trypan blue exclusion and MTT [(3-4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays …

Vector Delivery Technique Affects Gene Transfer In The Cornea In Vivo, Rajiv R. Mohan, Ajay Sharma, Tyler C. Cebulko, Ashish Tandon

Pharmacy Faculty Articles and Research

Purpose: This study tested whether controlled drying of the cornea increases vector absorption in mouse and rabbit corneas in vivo and human cornea ex vivo, and studied the effects of corneal drying on gene transfer, structure and inflammatory reaction in the mouse cornea in vivo.

Methods: Female C57 black mice and New Zealand White rabbits were used for in vivo studies. Donor human corneas were used for ex vivo experiments. A hair dryer was used for drying the corneas after removing corneal epithelium by gentle scraping. The corneas received no, once, twice, thrice, or five times warm air for …

Localization Of Angiotensin Converting Enzyme In Rabbit Cornea And Its Role In Controlling Corneal Angiogenesis In Vivo, Ajay Sharma, Daniel I. Bettis, John W. Cowden, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: The renin angiotensin system (RAS) has been shown to modulate vascular endothelial growth factor and angiogenesis. In this study we investigated (i) the existence of the RAS components angiotensin converting enzyme (ACE) and angiotensin II receptors (AT1 and AT2) in the rabbit cornea using in vitro and ex vivo models and (ii) the effect of enalapril, an ACE inhibitor, to inhibit angiogenesis in rabbit cornea in vivo.

Methods: New Zealand White rabbits were used. Cultured corneal fibroblasts and corneal epithelial cells were used for RNA isolation and cDNA preparation using standard molecular biology techniques. PCR was performed to …

"Transduction Efficiency Of Aav 2/6, 2/8 And 2/9 Vectors For Delivering Genes In Human Corneal Fibroblasts ", Ajay Sharma, Arkasubhra Ghosh, Eric T. Hansen, Jason M. Newman, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

In the present study, cellular tropism and relative transduction efficiency of AAV2/6, AAV2/8 and AAV2/9 vectors have been tested for the cornea using primary cultures of human corneal fibroblasts. The AAV6, AAV8 and AAV9 serotypes having AAV2 ITR plasmid encoding for alkaline phosphatase (AP) gene were generated by transfecting HEK293 cell line with pHelper, pARAP4 and pRep/Cap plasmids. Primary cultures of human corneal fibroblasts were exposed to AAV infectious particles at two different doses (1×105 and 2×105 MOI). Cytochemistry and enzyme assays were used to measure delivered transgene expression in samples collected at 4 and 30 hours after AAV infection …

Perspectives On The Practice Of Vaginal Birth After Caesarean Section In East Africa, Sikolia Wanyonyi, Abraham Mukaindo, William Stones

Obstetrics and Gynaecology, East Africa

Background: The increasing Caesarean section rates being observed in most facilities will ultimately result in a larger proportion of women with previous scar. Choices need to be made by both the patient and the health worker between attempted vaginal birth after Caesarean section (VBAC) and Elective Repeat Caesarean section (ERCS). Both practices are associated with perinatal risks and benefits that call for certain objectivity and prudence in decision making especially where resources are scarce.

Objective: To determine perceptions on the practice of vaginal birth after Caesarean section among maternity service providers in East Africa.

Design: A semi-qualitative cross sectional survey …

Knowledge, Attitudes And Practices Of Medical Students Regarding Needle Stick Injuries, Taimur Saleem, Umair Khalid, Sidra Ishaque, Afia Zafar

Department of Pathology and Laboratory Medicine

Objective: To ascertain knowledge, attitude and practices of medical students regarding needle stick injuries.
Methods: A cross sectional survey was conducted among the consenting medical students of 3rd, 4th and 5th years at a teaching hospital of Karachi, Pakistan. Convenience sampling was used. Pre-tested questionnaires were administered to approximately 70% of each class. Data was analyzed using SPSS version 16.0. Associations were assessed using chi-square test and Fisher's exact test. A p-value of <0.05 was considered as significant.
Results: The response rate of the survey was 85.7%. Sixty one students (33.9%) were from 3rd and 4th year each while 58 students (32.2%) were …

Successful Use Of Rituximab In Evans Syndrome And Refractory Immune Thrombocytopenic Purpura, Muhammad Kashif, Adnan Qureshi, Salman Naseem Adil, Mohammad Khurshid

Department of Pathology and Laboratory Medicine

Immune cytopenias are mediated by auto-antibodies produced by B-lymphocytes. Conventional treatment of immune-mediated haematological disorders includes immunosuppression with steroids and other immune modulating therapies and in some refractory cases, splenectomy. Response rates to conventional and second-line agents are variable and a proportion of patients require lifelong immunosuppression to maintain the disease in remission. Rituximab, an anti- CD 20 monoclonal antibody has gained widespread acceptance in the management of B-cell malignancies. Additionally, it has been used to treat the disorders associated with autoantibody production. We report herein the successful use of Rituximab in the treatment of two patients with autoimmune cytopenias …

Superficial Dsg2 Expression Limits Epidermal Blister Formation Mediated By Pemphigus Foliaceus Antibodies And Exfoliative Toxins., D Brennan, Ying Hu, Walid Medhat, A Dowling, M G Mahoney

Department of Dermatology and Cutaneous Biology Faculty Papers

Cell-cell adhesion mediated by desmosomes is crucial for maintaining proper epidermal structure and function, as evidenced by several severe and potentially fatal skin disorders involving impairment of desmosomal proteins. Pemphigus foliaceus (PF) and staphylococcal scalded skin syndrome (SSSS) are subcorneal blistering diseases resulting from loss of function of the desmosomal cadherin, desmoglein 1 (Dsg1). To further study the pathomechanism of these diseases and to assess the adhesive properties of Dsg2, we employed a recently established transgenic (Tg) mouse model expressing Dsg2 in the superficial epidermis. Neonatal Tg and wild type (WT) mice were injected with purified ETA or PF Ig. …

Effects Of Training On Physical Performance Wearing Personal Protective Equipment, David P. Swain, James A. Onate, Stacie I. Ringleb, Dayanand N. Naik, Marlene Demaio

Human Movement Studies & Special Education Faculty Publications

We evaluated the effects of wearing a weighted vest during 6 weeks of military-style training. Forty-three subjects were randomly assigned to a control group or a vest group (carrying 4-5 kg for 2 weeks, and 8-10 kg for 4 weeks), with 37 completing the study (17 vest, 20 control). Both groups performed stair climbing in addition to standard Marine Corps training for 1 hour, four times per week. Pre- and post-tests were performed while wearing military personal protective equipment, with the exception of the Marine Physical Readiness Test (PRT). Both groups significantly improved PRT scores (8.4% 3-mile run, 28-38% calisthenics) …

Aerobic Training Increases Skin Perfusion By A Nitric Oxide Mechanism In Type 2 Diabetes, Sheri R. Colberg, Laura C. Hill, Henri K. Parson, Kathleen S. Thomas, Aaron I. Vinik

Human Movement Studies & Special Education Faculty Publications

It is well known that a number of locally released vasodilatory and vasoconstrictive compounds can affect skin perfusion. This study investigated the effects of aerobic training on the contribution of nitric oxide (NO), prostaglandins (PG), and endothelial-derived hyperpolarizing factor (EDHF) in stimulated dorsal foot skin perfusion in individuals with type 2 diabetes (T2DM). Ten previously sedentary, older individuals with T2DM (57.0 ± 3.1 years) and nine sedentary controls (53.5 ± 3.2 years) were tested before and after undertaking six months of moderate aerobic training three times weekly in a supervised setting. All subjects underwent measurement of baseline (32°C) and heat-stimulated …

Plasmid Injection And Application Of Electric Pulses Alter Endogenous Mrna And Protein Expression In B16.F10 Mouse Melanomas, L. C. Heller, Y. L. Cruz, B. Ferraro, H. Yang, R. Heller

Bioelectrics Publications

The application of electric pulses to tissues causes cell membrane destabilization, allowing exogenous molecules to enter the cells. This delivery technique can be used for plasmid gene therapy. Reporter gene expression after plasmid delivery with eight representative published protocols was compared in B16.F10 mouse melanoma tumors. This expression varied significantly based on the pulse parameters utilized for delivery. To observe the possible influence of plasmid injection and/or pulse application on endogenous gene expression, levels of stress-related mRNAs 4 and 24 h after delivery were determined by PCR array. Increases in mRNA levels for several inflammatory chemokines and cytokines were observed …

Apoptosis Initiation And Angiogenesis Inhibition: Melanoma Targets For Nanosecond Pulsed Electric Fields, Xinhua Chen, Juergen F. Kolb, R. James Swanson, Karl H. Schoenbach, Stephen J. Beebe

Bioelectrics Publications

Many effective anti-cancer strategies target apoptosis and angiogenesis mechanisms. Applications of non-ionizing, nanosecond pulsed electric fields (nsPEFs) induce apoptosis in vitro and eliminate cancer in vivo; however in vivo mechanisms require closer analysis. These studies investigate nsPEF-induced apoptosis and anti-angiogenesis examined by fluorescent microscopy, immunoblots, and morphology. Six hours after treatment with one hundred 300 ns pulses at 40 kV/cm, cells transiently expressed active caspases indicating that caspase-mediated mechanisms. Three hours after treatment transient peaks in Histone 2AX phosphorylation coincided with terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells and pyknotic nuclei, suggesting caspase-independent mechanisms on nuclei/DNA. Large …

Impact Of An Interprofessional Central Venous Catheter Insertion Training Program, James P. Orlando Edd, Andrew Miller Do, William Bond Md, Ms, Valerie A. Rupp Rn, Bsn, Bryan G. Kane Md, Cindy Umbrell Rn, Msn, Michael Pasquale Md, Elizabeth Verheggen Phd, Elliot J. Sussman Md, Mba

Department of Emergency Medicine

No abstract provided.

The Correlation Between Adolescent Driving Behaviors, Robert D. Barraco Md, Bryan G. Kane Md, Shawna Murphy Do, Valerie Rupp Rn, Bsn, Kimberly Hamilton Ba, Traci Anselmo Do, James F. Reed Iii Phd

Department of Emergency Medicine

No abstract provided.

Patient Attitudes Regarding Consent For Emergency Department Computed Tomography Scans, Michael Weigner Md, Hilary Basham Do, Kate M. Dewar Do, Valerie A. Rupp Rn, Bsn, Marna R. Greenburg Do, Mph

Department of Emergency Medicine

No abstract provided.

Spontaneous Hemoperitoneum Following Colonoscopy, Christine Whylings Do, Gavin C. Barr Jr., Md, Kathleen Kane Md

Department of Emergency Medicine

No abstract provided.

A Feasibility Study To Determine If Inexpensive Commercial Coolers Maintain Normal Saline Temperatures At 4ºc, Robert Tomsho Do, Ms, Karen Pheasant Do, Valerie A. Rupp Rn, Bsn, Kathleen E. Kane Md, Bryan G. Kane Md

Department of Emergency Medicine

No abstract provided.

A Qualitative Review Of Differential Diagnosis Generators, William Bond Md, Ms, Linda M. Schwartz Mde, Ahip, Cm, Kevin R. Weaver Do, Donald Levick Md, Mba, Michael Guliano Md, Med, Mhpe, Mark L. Graber Md

Department of Emergency Medicine

No abstract provided.

Cardiopulmonary Resuscitation Prescription Program: A Prospective Randomized Pilot Study, Marna R. Greenberg Do, Mph, Facep, Gavin Barr Md, Valerie Rupp Rn, Bsn, Nainesh C. Patel Md, Kevin R. Weaver Do, Kimberly Hamilton Ba, James F. Reed Iii Phd

Department of Emergency Medicine

No abstract provided.

Does Intra-Amniotic Inflammation Influence Pregnancy Outcome After Cerclage Orprogesterone (17ohp-C) Therapy For Midtrimester Short Cervix?, Orion Rust Md, Daniel Kiefer Md, Sean M. Keeler Md, Morgan R. Peltier Phd, Jolene C. Muscat Md, Nazeeh Hanna Md, Anthony M. Vintzileos Md, Cande V. Ananth Phd, Mph

Department of Obstetrics & Gynecology

No abstract provided.

Self-Examination For Breast And Testicular Cancers: A Community-Based Intervention Study., Khairunnisa Shallwani, Rozina Ramji, Tazeen S. Ali, Ali Khan Khuwaja

Department of Radiation Oncology

The prevalence of cancers is growing rapidly in all parts of the word and Pakistan is no exception. Prevention is the best option to tackle this rising epidemic and screening, early detection and health awareness programs are cornerstones in this regard. A community-based interventional study was therefore her conducted to assess the effect of health education intervention about knowledge and practice of self-breast examination (SBE) among women and self-testicular examination (STE) among men. A total of 127 (70 females and 57 males) adults (>or=18 years) from an urban community of Karachi, Pakistan were included after giving informed consent. Interventions …

Differential Gene Expression Profile Of Retinoblastoma Compared To Normal Retina., Arupa Ganguly, Carol L Shields

Wills Eye Hospital Papers

PURPOSE: The retinoblastoma gene (RB1) is a tumor suppressor gene that was first discovered in a rare ocular pediatric tumor called retinoblastoma (RB). The RB1 gene is essential for normal progression through the cell cycle and exerts part of its function through the family of transcription factors (E2F) and many other intermediaries. In the absence of normal RB1, genomic instability and chromosomal aberrations accumulate, leading to tumor initiation, progression, and ultimately metastasis. The purpose of this report was to identify the molecular pathways that are deregulated in retinoblastoma.

METHODS: We compared gene expression signatures of matched normal retinal tissue and …

Impact Of Education On Physician Attitudes Toward Computed Tomography (Ct) Utilization And Consent, Michael B. Weigner Md, Kate M. Dewar Do, Hilary F. Basham Do, Valerie A. Rupp Rn, Bsn, Marna R. Greenberg Do, Mph

Department of Emergency Medicine

No abstract provided.

Bicarbonate Enhances Expression Of The Endocarditis And Biofilm Associated Pilus Locus, Ebpr-Ebpabc, In Enterococcus Faecalis, Agathe Bourgogne, L Charlene Thomson, Barbara E Murray

Journal Articles

BACKGROUND: We previously identified ebpR, encoding a potential member of the AtxA/Mga transcriptional regulator family, and showed that it is important for transcriptional activation of the Enterococcus faecalis endocarditis and biofilm associated pilus operon, ebpABC. Although ebpR is not absolutely essential for ebpABC expression (100-fold reduction), its deletion led to phenotypes similar to those of an ebpABC mutant such as absence of pili at the cell surface and, consequently, reduced biofilm formation. A non-piliated ebpABC mutant has been shown to be attenuated in a rat model of endocarditis and in a murine urinary tract infection model, indicating an important participation …

Brachial Artery Aneursym With “Blue Finger Syndrome” After Ligation Of An Arterio-Venous Fistula, Ramon Garza, Iii Md, Dale A. Dangleben Md, John F. Welkie Md

Department of Surgery

No abstract provided.

Our Grandparents, Our Parents, Our Future Selves: Optimizing Function In Old Age., Thomas Michael Gill

Center for Policy Research

Most of my research at Yale University School of Medicine over the past several years has focused on identifying older adults at risk of functional decline and disability, identifying events that may precipitate the transition from functional independence to disability, and developing strategies to postpone or reduce frailty and disability. As a result of the Precipitating Events Project (PEP) and other research conducted by the Yale Center on Aging/Pepper Center, we now realize that age is only a proxy for other factors that lead to disability, and that some of these factors can be modified to reduce the risk of …

Parastomal Patch For Laparoscopic Repair Of Parastomal Hernia: Description Of The Technique, Courtney Edwards Md, Dale A. Dangleben Md, Erik J. Teicher Md, Peter Rovito Md

Department of Surgery

No abstract provided.

The Nonpsychoactive Cannabinoid Cannabidiol Inhibits 5-Hydroxytryptamine3a Receptor-Mediated Currents In Xenopus Laevis Oocytes, Keun-Hang Susan Yang, Sehamuddin Galadari, Dmytro Isaev, Georg Petroianu, Toni S. Shippenberg, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

The effect of the plant-derived nonpsychotropic cannabinoid, cannabidiol (CBD), on the function of hydroxytryptamine (5-HT)3A receptors expressed in Xenopus laevis oocytes was investigated using two-electrode voltage-clamp techniques. CBD reversibly inhibited 5-HT (1 μM)-evoked currents in a concentration-dependent manner (IC50 = 0.6 μM). CBD (1 μM) did not alter specific binding of the 5-HT3A antagonist [3H]3-(5-methyl-1H-imidazol-4-yl)-1-(1-methylindol-3-yl)propan-1-one (GR65630), in oocytes expressing 5-HT3A receptors. In the presence of 1 μM CBD, the maximal 5-HT-induced currents were also inhibited. The EC50 values were 1.2 and 1.4 μM, in the absence and presence of CBD, indicating that CBD acts as a noncompetitive antagonist of 5-HT3 …