Medical Specialties Commons^™

Regulation And Targeting Of Fyn In Human Cutaneous Squamous Cell Carcinoma, Sarah Fenton

Dissertations

Fyn, a member of the Src family kinases, is an oncogene in murine epidermis and is associated with cell-cell adhesion turnover and migration. Introduction of active H-Ras(G12V) into the HaCaT human keratinocyte cell line resulted in upregulation of FYN mRNA (200-fold) and protein, but did not increase the expression of other SFKs. We identified two nucleotides 74 bases upstream of the human FYN gene transcription start site as necessary for FYN upregulation in HaCaT-Ras cells. Further studies identified Lef-1 as the transcription factor most likely binding to this site and mediating FYN upregulation.

Transduction of active Ras or Fyn was …

Regulation Of Glucose Homeostasis By The Phlpp1 Phosphatase, Kara L. Larson

Theses and Dissertations--Molecular and Cellular Biochemistry

Type 2 diabetes mellitus is a metabolic disease that affects one in ten people in the United States. It is caused by a combination of genetics and lifestyle factors. Disease progression begins with insulin resistance in peripheral tissues followed by pancreatic beta-cell failure. The mechanisms behind disease progression are not completely understood. PH domain leucine rich repeat protein phosphatase 1 (PHLPP1) is a known regulator of Akt and other members of the AGC kinase family. Akt has been established to play a role in numerous metabolic signaling pathways, including insulin action. It is hypothesized that as a regulator of Akt, …

Within-Day Test-Retest Reliability Of Transcranial Magnetic Stimulation Measurements Of Corticomotor Excitability For Gastrocnemius And Tibialis Anterior Muscles, Beth E. Fisher, Ya-Yun Lee, Todd E. Davenport, Stephen F. Reischl, Elizabeth Ruckert, Kornelia Kulig

School of Pharmacy Faculty Articles

Background: Manual therapy interventions targeting the talocrural joint can improve gait and balance functions in individuals following ankle sprains. Less is known about the underlying mechanisms of functional improvements after manual therapy. One hypothesis involves change in corticomotor excitability (CE) following manual therapy procedures. Transcranial magnetic stimulation (TMS) is a brain imaging method that could provide important information regarding potential changes in CE associated with manual therapy techniques applied to the talocrural joint. However, within-day reliability of TMS to measure CE must first be established in order to measure CE changes associated with manual therapy procedures.

Objective: To determine the …

Β-Lactamase Production And Antimicrobial Susceptibility Pattern Of Moraxella Catarrhalis Isolates: Report From Pakistan, Sadia Omer Sheikh, Naima Fasih, Seema Irfan, Afia Zafar

Department of Pathology and Laboratory Medicine

Objective: To assess the frequency of β-lactamase production and antimicrobial resistance in Moraxella catarrhalis isolated from clinical specimens in Pakistan. Methods: This cross sectional study (January to December 2010) was conducted in clinical microbiology laboratory of Aga Khan University Hospital. A total of 97 clinical respiratory specimens growing Moraxella catarrhalis were included. Frequency of β-lactamase production and antimicrobial resistance rates against ampicillin, erythromycin, ciprofloxacin and tetracycline were noted by performing minimum inhibitory concentration (MIC). MICs were calculated as MIC50 and MIC90.
Results: β-Lactamase production was detected in 84% of isolates, which correlated well with high MIC of …

Expression Of The Androgen Receptor, Pakt, And Ppten In Breast Cancer And Their Potential In Prognostication, Aisha Sultana, Romana Idress, Zulfiqar Ali Naqvi, Iqbal Azam, Shaista Khan, Anwar Ali Siddiqui, El Nasir Lalani

Department of Pathology and Laboratory Medicine

BACKGROUND: Importance of androgen receptor (AR) as an independent prognostic marker in Pakistani women with breast cancer (BCa) remains unexplored. Our aim was to identify the expression and potential prognostic value of AR, its upstream regulator (pAkt) and target gene (pPTEN) in invasive BCa.
METHODS: This study used a cohort of 200 Pakistani women with invasive BCa diagnosed during 2002-2011. Expression of AR, pAkt and pPTEN was determined on formalin fixed paraffin embedded tissue sections by immunohistochemistry. The association of AR, pAkt and pPTEN with clinicopathological parameters was determined. Survival analyses were undertaken on patients with ≥ 5 years of …

Ovarian Sex Cord Stromal Tumours In Children And Young Girls - A More Than Two Decade Clinicopathological Experience In A Developing Country, Pakistan, Saroona Haroon, Romana Idrees, Aleena Zia, Aisha Memon, Saira Fatima, Naila Kayani

Department of Pathology and Laboratory Medicine

Background: Ovarian sex-cord stromal tumours (SCST) are rare, and relatively infrequent in children. These have to be distinguished from more common germ cell tumors in children and also from benign epithelial neoplasms.
Objectives: The purpose of our study was to report the clinical and pathological findings in young patients with these tumours in our population.
Material and Methods: The present observational cross-sectional study included all subjects SCST, in Aga Khan University Hospital Histopathology Laboratory, Karachi, Pakistan, from January 1992 till July 2013.
Results: Of the total of 513 SCSTs presented during the study period, 39 fulfilled inclusion criteria and were …

Pleomorphic Lobular Carcinoma Of The Male Breast With Axillary Lymph Node Involvement: A Case Report And Review Of Literature, Muhammad Nauman Zahir, Khurram Minhas, Munira Shabbir-Moosajee

Department of Pathology and Laboratory Medicine

Background: Carcinoma of the male breast is responsible for less than 1% of all malignancies in men but the incidence is rising. Invasive ductal carcinoma is the most common histological subtype while invasive lobular carcinoma is responsible for only 1.5% of the total cases of which pleomorpic lobular carcinoma is an extremely rare variant. We report the case of a gentleman with node positive, pleomorphic lobular carcinoma of the breast.
Case Presentation: An elderly gentleman with a past history of type 2 diabetes and long term ethanol use presented to us with a self-discovered palpable lump in the left breast. …

Clinical And Biochemical Characteristics Of Children With Juvenile Idiopathic Arthritis, Shakeel Ahmed, Syed Rehan Ali, Sidra Ishaque, Nabil Sami

Department of Paediatrics and Child Health

Objective: To determine the clinical and biochemical characteristics of children with Juvenile Idiopathic Arthritis (JIA) at a tertiary care centre in Karachi, Pakistan.

Study Design: A descriptive study.

Place and Duration of Study: Paediatric Rheumatology Clinic of The Aga Khan University Hospital (AKUH), Karachi, from January 2008 to December 2011.

Methodology: Clinical and laboratory profile and outcome of children less than 15 years of age attending the Paediatric Rheumatology Clinic of the Aga Khan University, Karachi with the diagnosis of Juvenile Idiopathic Arthritis according to International League against Rheumatism were studied. These children were classified into different types of JIA; …

The Conceptual Framework And Assessment Methodology For The Systematic Reviews Of Community-Based Interventions For The Prevention And Control Of Infectious Diseases Of Poverty, Zohra S. Lassi, Rehana A. Salam, Jai K. Das, Zulfiqar A. Bhutta

Department of Paediatrics and Child Health

This paper describes the conceptual framework and the methodology used to guide the systematic reviews of community-based interventions (CBIs) for the prevention and control of infectious diseases of poverty (IDoP). We adapted the conceptual framework from the 3ie work on the 'Community-Based Intervention Packages for Preventing Maternal Morbidity and Mortality and Improving Neonatal Outcomes' to aid in the analyzing of the existing CBIs for IDoP. The conceptual framework revolves around objectives, inputs, processes, outputs, outcomes, and impacts showing the theoretical linkages between the delivery of the interventions targeting these diseases through various community delivery platforms and the consequent health impacts. …

Ahead Of Their Time: The Story Of Alice Berry Graham And Katharine Berry Richardson, The Founders Of Children's Mercy Hospital In Kansas City, Jane F. Knapp Md, Robert Schremmer

Posters

Describes the founding of Children's Mercy Hospital through the story of its founders, Katharine Berry Richardson and Alice Berry Graham.

Update Of The Who/Iuis Allergen Nomenclature Database Based On Analysis Of Allergen Sequences, C. Radauer, A. Nandy, F. Ferreira, Richard E. Goodman, J. N. Larsen, J. Lidholm, A. Pomés, M. Raulf-Heimsoth, P. Rozynek, W. R. Thomas, Heimo Breiteneder

Department of Food Science and Technology: Faculty Publications

The IUIS Allergen Nomenclature Sub-Committee, under the auspices of the World Health Organization and the International Union of Immunological Societies, maintains the systematic nomenclature of allergenic proteins and publishes a database of approved allergen names on its Web site, www.allergen.org. In this paper, we summarize updates of allergen names approved at the meetings of the committee in 2011 through 2013. These changes reflect recent progress in identification, cloning, and sequencing of allergens. The goals of this update were to increase consistency in the classification of allergens, isoallergens, and variants and in the incorporation of the evolutionary classification of proteins into …

A Prospective Study Of Periodontal Disease And Risk Of Gastric And Duodenal Ulcer In Male Health Professionals, Matthew R. Boylan, Hamed Khalili, Edward S. Huang, Dominique S. Michaud, Jacques Izard, Kaumudi J. Joshipura, Andrew T. Chan

Department of Food Science and Technology: Faculty Publications

Periodontal disease is characterized by microbial shifts within the oral cavity and chronic inflammation of the gingival tissue, and can lead to tooth loss. Several studies support an association between periodontal disease and risk of chronic systemic conditions, including vascular disease, chronic obstructive pulmonary disease, diabetes mellitus, and cancer, including gastric adenocarcinoma. These associations may be mediated by systemic inflammation, the immune response to periodontal infection, or direct invasion by pathogens. Previous studies of periodontal disease and risk of peptic ulcer have been limited by cross-sectional design, diagnoses that were not confirmed by medical record review, and a lack of …

Development And Evolution Of Risk Assessment For Food Allergens, Rene W. R. Crevel, Joseph Baumert, Athanasia Baka, Geert Houben, André C. Knulst, Astrid Kruizinga, Stefano Luccioli, Stephen L. Taylor, Charlotte B. Madsen

Department of Food Science and Technology: Faculty Publications

The need to assess the risk from food allergens derives directly from the need to manage effectively this food safety hazard. Work spanning the last two decades dispelled the initial thinking that food allergens were so unique that the risk they posed was not amenable to established risk assessment approaches and methodologies. Food allergens possess some unique characteristics, which make a simple safety assessment approach based on the establishment of absolute population thresholds inadequate. Dose distribution modelling of MEDs permitted the quantification of the risk of reaction at the population level and has been readily integrated with consumption and contamination …

Translating Reference Doses Into Allergen Management Practice: Challenges For Stakeholders, René W. R. Crevel, Joseph Baumert, Stefano Luccioli, Athanasia Baka, Sue Hattersley, Jonathan O.B. Hourihane, Stefan Ronsmans, Frans Timmermans, Rachel Ward, Yong-Joo Chung

Department of Food Science and Technology: Faculty Publications

Risk assessment describes the impact of a particular hazard as a function of dose and exposure. It forms the foundation of risk management and contributes to the overall decision-making process, but is not its endpoint. This paper outlines a risk analysis framework to underpin decision-making in the area of allergen cross-contact. Specifically, it identifies challenges relevant to each component of the risk analysis: risk assessment (data gaps and output interpretation); risk management (clear and realistic objectives); and risk communication (clear articulation of risk and benefit). Translation of the outputs from risk assessment models into risk management measures must be informed …

Update On Intra-Arterial Chemotherapy For Retinoblastoma., Mario Zanaty, Guilherme Barros, Nohra Chalouhi, Md, Robert M Starke, Philip Manasseh, Stavropoula I. Tjoumakaris, Carol L Shields, David Hasan, Ketan Bulsara, Robert H. Rosenwasswer Md, Pascal Jabbour Md

Department of Neurosurgery Faculty Papers

The tools for managing retinoblastoma have been increasing in the past decade. While globe-salvage still relies heavily on intravenous chemotherapy, tumors in advanced stage that failed chemotherapy are now referred for intra-arterial chemotherapy (IAC) to avoid enucleation. However, IAC still has many obstacles to overcome. We present an update on the indications, complications, limitations, success, and technical aspects of IAC. Given its safety and high efficacy, it is expected that IAC will replace conventional strategies and will become a first-line option even for tumors that are amenable for other strategies.

Cell- And Virus-Mediated Regulation Of The Barrier-To-Autointegration Factor’S Phosphorylation State Controls Its Dna Binding, Dimerization, Subcellular Localization, And Antipoxviral Activity, Augusta Jamin, April Wicklund, Matthew S. Wiebe

Nebraska Center for Virology: Faculty Publications

Barrier-to-autointegration factor (BAF) is a DNA binding protein with multiple cellular functions, including the ability to act as a potent defense against vaccinia virus infection. This antiviral function involves BAF’s ability to condense double-stranded DNA and subsequently prevent viral DNA replication. In recent years, it has become increasingly evident that dynamic phosphorylation involving the vaccinia virus B1 kinase and cellular enzymes is likely a key regulator of multiple BAF functions; however, the precise mechanisms are poorly understood. Here we analyzed how phosphorylation impacts BAF’s DNA binding, subcellular localization, dimerization, and antipoxviral activity through the characterization of BAF phosphomimetic and unphosphorylatable …

Characterization Of A Dual-Tropic Human Immunodeficiency Virus (Hiv-1) Strain Derived From The Prototypical X4 Isolate Hxbc2, Shi-Hua Xiang, Beatriz Pacheco, Dane Bowder, Wen Yuan, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus type 1 (HIV-1) coreceptor usage and tropism can be modulated by the V3 loop sequence of the gp120 exterior envelope glycoprotein. For coreceptors, R5 viruses use CCR5, X4 viruses use CXCR4, and dual-tropic (R5X4) viruses use either CCR5 or CXCR4. To understand the requirements for dual tropism, we derived and analyzed a dual-tropic variant of an X4 virus. Changes in the V3 base, which allow gp120 to interact with the tyrosine-sulfated CCR5 N-terminus, and deletion of residues 310/311 in the V3 tip were necessary for efficient CCR5 binding and utilization. Thus, both sets of V3 changes allowed …

Live Siv Vaccine Correlate Of Protection: Immune Complex-Inhibitory Fc Receptor Interactions That Reduce Target Cell Availability, Anthony J. Smith, Stephen W. Wietgrefe, Liang Shang, Cavan S. Reilly, Peter J. Southern, Katherine E. Perkey, Lijie Duan, Heinz Kohler, Sybille Muller, James Robinson, John V. Carlis, Qingsheng Li, R. Paul Johnson, Ashley T. Haase

Nebraska Center for Virology: Faculty Publications

Principles to guide design of an effective vaccine against HIV are greatly needed, particularly to

protect women in the pandemic’s epicentre in Africa. We have been seeking these principles by

identifying correlates of the robust protection associated with SIV_mac239Δnef vaccination in the

SIV-rhesus macaque animal model of HIV-1 transmission to women. We have identified one

correlate of SIV_mac239Δnef protection against vaginal challenge as a resident mucosal system for

SIV-gp41 trimer antibody production and neonatal Fc receptor (FcRn)-mediated concentration of

these antibodies on the path of virus entry to inhibit establishment of infected founder populations

at the …

Review Of Epidemiology And Transmission Of Kaposi’S Sarcoma-Associated Herpesvirus, Veenu Minhas, Charles Wood

Nebraska Center for Virology: Faculty Publications

This review summarizes the current knowledge pertaining to Kaposi sarcoma-associated herpesvirus (KSHV) epidemiology and transmission. Since the identification of KSHV twenty years ago, it is now known to be associated with Kaposi’s sarcoma (KS), primary effusion lymphoma, and multicentric Castleman’s disease. Many studies have been conducted to understand its epidemiology and pathogenesis and their results clearly show that the worldwide distribution of KSHV is uneven. Some geographical areas, such as sub-Saharan Africa, the Mediterranean region and the Xinjiang region of China, are endemic areas, but Western Europe and United States have a low prevalence in the general population. This makes …

Seroprevalence Of Human Herpesvirus 8 And Hepatitis C Virus Among Drug Users In Shanghai, China, Tiejun Zhang, Ying Liu, Yuyan Zhang, Jun Wang, Veenu Minhas, Charles Wood, Na He

Nebraska Center for Virology: Faculty Publications

To elucidate and compare the seroprevalence of human herpesvirus 8 (HHV8) and hepatitis C virus (HCV) among Chinese drug users, a cross-sectional study of 441 participants, was conducted in Shanghai, China, from 2012 through 2013. Seventy-seven (17.5%) participants were found to be positive for HHV8 antibodies, while 271 (61.5%) participants were positive for HCV. No significant association between HHV8 seropositivity and drug use characteristics, sexual behaviors, HCV, or syphilis was observed. In contrast, a statistically significant association between HCV seropositivity and injected drug history (OR, 2.18, 95% CI 1.41–3.37) was detected, whereas no statistically significant association between HCV seropositivity and …

Vaccines Within Vaccines: The Use Of Adenovirus Types 4 And 7 As Influenza Vaccine Vectors, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

adenovirus Types 4 and 7 (ad4 and ad7) are associated with acute respiratory distress (aRD). In order to prevent wide- spread ad-associated aRD (ad-aRD) the United states military immunizes new recruits using a safe and effective lyophi- lized wildtype ad4 and ad7 delivered orally in an enteric-coated capsule. We cloned ad4 and ad7 and modified them to express either a GFP-Luciferase (GFPLuc) fusion gene or a centralized influenza H1 hemagglutinin (Ha1-con). BaLB/c mice were injected with GFPLuc expressing viruses intramuscularly (i.m.) and intranasally (i.n.). ad4 induced significantly higher luciferase expression levels as compared with ad7 by both routes. ad7 transduction …

Sulfites, Steve L. Taylor, Robert K. Bush, Julie A. Nordlee

Department of Food Science and Technology: Faculty Publications

Key Concepts

Sulfites are frequently used food and drug additives.

Ingestion of sulfite residues has been documented to trigger asthmatic reactions in sensitive individuals.

Sulfite-induced asthma occurs in less than 5% of asthmatic individuals, and those with severe, persistent asthma are at greatest risk.

The diagnosis of sulfite-induced asthma is best made by blinded oral challenge with assessment of lung function.

Labeling regulations in the United States alert sulfite-sensitive individuals to the presence of sulfites in foods, which must then be avoided.

Environmental And Occupational Factors Associated With Chronic Myeloid Leukemia: A Case-Control Study, R. Kasmani, N.A. Othieno-Abinya, M.T. Singh Riyat, G.W. Kiarie, Peter Wanzala

Pathology, East Africa

Background: The relationship between chronic myeloid leukemia (CML) and a broad range of exposures to occupational and environmental factors known to cause leukemia in general is limited. CML is by and large incurable and treatment is just palliative and life prolonging, with high case fatality rate, even in the best centers. Furthermore treatment is very expensive. Identification of leukemogenic factors is therefore important if this can lead to simple public health interventions.

Objective: The objective was to determine key environmental and occupational exposure factors that may be associated with CML.

Methods: This was a case-control study involving CML …

Low Prevalence Of Methicillin Resistant As Determined By An Automated Identification System In Two Private Hospitals In Nairobi, Kenya: A Cross Sectional Study, Geoffrey Omuse, Beatrice Kabera, Gunturu Revathi

Pathology, East Africa

Background: Staphylococcus aureus (S.aureus) is a major cause of both healthcare and community acquired infections. In developing countries, manual phenotypic tests are the mainstay for the identification of staphylococci with the tube and slide coagulase tests being relied upon as confirmatory tests for S. aureus. The subjectivity associated with interpretation of these tests may result in misidentification of coagulase negative staphylococci as S.aureus. Given that antibiotic resistance is more prevalent in CONS, this may result in over estimation of methicillin resistant S.aureus (MRSA) prevalence.

Methods: A review of susceptibility data from all non-duplicate S.aureus isolates generated between March 2011 and …

Deferiprone Versus Deferoxamine In Sickle Cell Disease: Results From A 5-Year Long-Term Italian Multi-Center Randomized Clinical Trial., Giusi Calvaruso, Angela Vitrano, Rosario Di Maggio, Samir K. Ballas, Martin H Steinberg, Paolo Rigano, Massimiliano Sacco, Paul Telfer, Disma Renda, Rita Barone, Aurelio Maggio

Cardeza Foundation for Hematologic Research

Blood transfusion and iron chelation currently represent a supportive therapy to manage anemia, vasculopathy and vaso-occlusion crises in Sickle-Cell-Disease. Here we describe the first 5-year long-term randomized clinical trial comparing Deferiprone versus Deferoxamine in patients with Sickle-Cell-Disease. The results of this study show that Deferiprone has the same effectiveness as Deferoxamine in decreasing body iron burden, measured as repeated measurements of serum ferritin concentrations on the same patient over 5-years and analyzed according to the linear mixed-effects model (LMM) (p=0.822). Both chelators are able to decrease, significantly, serum ferritin concentrations, during 5-years, without any effect on safety (p=0.005). Moreover, although …

Primary Stroke In A Woman With Sickle Cell Anemia Responsive To Hydroxyurea Therapy., Samir K. Ballas, Ubaldo E. Martinez-Outshoorn, Michael P. Savage

Cardeza Foundation for Hematologic Research

The most common cause of stroke in children with sickle cell anemia is infarction due to ischemia. In adults, however, stroke is most commonly hemorrhagic in nature. Other causes of stroke in patients with sickle cell disease are very rare. In this short communication, we describe a woman with sickle cell anemia responsive to hydroxyurea (HU) therapy who had primary stroke due to paradoxical embolization caused by a large atrial septal defect. Successful management of the stroke included surgical closure of the defect with trans-esophageal echocardiographic guidance. To the best of our knowledge, this is the first patient with sickle …

Assessing Prevalence Of Known Risk Factors In A Regional Central Kentucky Medical Center Heart Failure Population As An Approach To Assessment Of Needs For Development Of A Program To Provide Targeted Services To Reduce 30 Day Readmissions, Christeen Ivy Broaddus

DNP Projects

Abstract

Objectives:

1. Determine demographic, physiologic, and laboratory characteristics at time of admission of the heart failure (HF) population in a regional acute care facility in Central Kentucky through review of patient electronic medical records.
2. Determine which HF population characteristics are significantly associated with readmissions to the hospital.
3. Provide identification of the statistically significant common characteristics of the HF population to this facility so that they may work towards development of an electronic risk for readmission predictive instrument.

Design: Retrospective chart review.

Setting: Regional acute care facility in Central Kentucky.

Participants: All patients (n = 175) with a diagnosis or history …

Assessing Blood Pressure Control In Primary Care, Ashley W. Guiliani

DNP Projects

Purpose: To evaluate provider adherence to JNC 7 by assessing documentation of blood pressure control and interventions in the absence of control in order to assist providers in reaching Healthy People 2020 goal of blood pressure control.

Methods: A retrospective chart review was conducted for patients with essential hypertension. Data collected included blood pressure, use of a home blood pressure log, documentation of blood pressure medication compliance, and provider interventions in the absence of blood pressure control across three visits. A provider survey regarding provider barriers to blood pressure control was also completed.

Results: All surveyed providers were aware and …

The Association Of Primary Care Physician Supply To The Prevalence Of Diabetes, Obesity, Smoking, And Hypertension In Georgia, Dennis L. White

MUSC Theses and Dissertations

The primary focus of this study was to compare primary care physician supply throughout Georgia to the prevalence of diabetes, obesity, smoking, and hypertension county by county, identifying potential issues related to primary care physician supply. This research identified the distribution of the primary care physician workforce across Georgia; county by county, and in urban and rural areas, and across public health districts. Then, the research identifies whether the current supply of Georgia primary care physicians is sufficient to meet the growing need for population healthcare. Studying the area of primary care physician supply in correlation to the prevalence of …

Parkinson's Diagnosis From The Caregiver's Perspective, Helen Maree Bradley

Theses : Honours

Parkinson’s disease (Parkinson’s) is a progressive neurodegenerative disorder. The irreversible and accumulating disability experienced means that people with Parkinson’s progressively lose their autonomy, eventually requiring complete care. Consequently, Parkinson’s significantly impacts sufferers and the people who care for them. Informal care, predominantly provided by female spouses becomes exceptionally demanding over time, and caregivers experience significant morbidity. Stress manifests across all stages of the caregiving trajectory, with diagnosis reported as a particularly stressful period for caregivers; however, few attempts have been made to understand what makes it stressful. The current study explored female spousal caregivers’ subjective experience of the Parkinson’s diagnosis, …