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Role Of Human Protein Disulfide Isomerase (Pdi) In The Redox Regulation Of Anthrax Receptor 2 (Antxr2), Naima Mohamed Alshrif

Open Access Theses & Dissertations

Anthrax is an acute infectious disease caused by B. anthracis, a gram-positive and spore-forming bacterium. Anthrax toxin is a tripartite AB toxin composed of a receptor binding/pore-forming moiety, protective antigen (PA), and two catalytic moieties, edema factor (EF) and lethal factor (LF). Anthrax toxin PA binds to cell-surface receptors, where it gets activated by furin, and assembles into a ring-like heptameric structure. The toxin-receptor complex is internalized into endosomes where the acidic pH triggers PA pore formation on the endosomal membrane that translocates the toxin catalytic moieties. Recent study has shown that anthrax toxin receptors play a critical role in …

Mobilizing Subdominant Hiv-Specific Ctls As A Novel Vaccine Strategy, Margaret Christina Costanzo

Open Access Theses & Dissertations

To overcome the extreme antigenic diversity of HIV, there is increasing interest in developing vaccines that target CD8 T cell responses to conserved regions of the viral proteome. Understanding the immunogenic potential of these domains is therefore critical for the success of this vaccine strategy. CD8 T cell responses to conserved domains restricted by the "neutral" and highly prevalent HLA-A2 allele have not been extensively characterized. Here we describe a novel essentially invariant 10-mer epitope in HIV Gag (p2414-23, RTLNAWVKVV (RV10)) in that it is expressed by the majority HIV isolates from all clades. Here we examined the character of …

Tracking Of In-111-Labeled Human Umbilical Tissue-Derived Cells (Hutc) In A Rat Model Of Cerebral Ischemia Using Spect Imaging, Ali S. Arbab, Christine Thiffault, Bradford Navia, Stephen J. Victor, Klaudyne Hong, Li Zhang, Quan Jiang, Nadimpalli Rs Varma, Asm Iskander, Michael Chopp

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

In order to increase understanding of how infused cells work, it becomes important to track their initial movement, localization, and engraftment efficiency following transplantation. However, the available in vivo cell tracking techniques are suboptimal. The study objective was to determine the biodistribution of intravenously administered Indium-111 (In-111) oxine labeled human umbilical tissue-derived cells (hUTC) in a rat model of transient middle cerebral occlusion (tMCAo) using single photon emission computed tomography (SPECT).

Methods

Rats received 3 million In-111 labeled hUTC (i.v.) 48 hrs after tMCAo. Following the administration of either hUTC or equivalent dose of In-111-oxine (18.5 MBq), animals …

Fibroblast-Secreted Hepatocyte Growth Factor Mediates Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance In Triple-Negative Breast Cancers Through Paracrine Activation Of Met, Kelly L. Mueller, Julie M. Madden, Gina L. Zoratti, Charlotte Kuperwasser, Karin List, Julie L. Boerner

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown clinical efficacy in lung, colon, and pancreatic cancers. In lung cancer, resistance to EGFR TKIs correlates with amplification of the hepatocyte growth factor (HGF) receptor tyrosine kinase Met. Breast cancers do not respond to EGFR TKIs, even though EGFR is overexpressed. This intrinsic resistance to EGFR TKIs in breast cancer does not correlate with Met amplification. In several tissue monoculture models of human breast cancer, Met, although expressed, is not phosphorylated, suggesting a requirement for a paracrine-produced ligand. In fact, HGF, the ligand for Met, is not …

Signaling In Colon Cancer Stem Cells, Sanchita Roy, Adhip Pn Majumdar

Wayne State University Associated BioMed Central Scholarship

Abstract

Hdm2 Antagonist Mi-219 (Spiro-Oxindole), But Not Nutlin-3 (Cis-Imidazoline), Regulates P53 Through Enhanced Hdm2 Autoubiquitination And Degradation In Human Malignant B-Cell Lymphomas, Angela M. Sosin, Angelika M. Burger, Aisha Siddiqi, Judith Abrams, Ramzi M. Mohammad, Ayad M. Al-Katib

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Lymphomas frequently retain wild-type (wt) p53 function but overexpress HDM2, thereby compromising p53 activity. Therefore, lymphoma is a suitable model for studying the therapeutic value of disrupting the HDM2-p53 interaction by small-molecule inhibitors (SMIs). HDM2 have been developed and are under various stages of preclinical and clinical investigation. Previously, we examined the anti-lymphoma activity of MI-319, the laboratory grade of a new class of HDM2 SMI, the spiro-oxindole, in follicular lymphoma. Since then, MI-219, the clinical grade has become readily available. This study further examines the preclinical effects and mechanisms of MI-219 in a panel of human lymphoma …

The Proton-Coupled Folate Transporter: Biology And Therapeutic Applications To Cancer, Sita Desmoulin

Wayne State University Dissertations

Folates are essential cofactors of tumor cell proliferation and survival required for nucleotide biosynthesis and amino acid metabolism. In cancer therapy, inhibition of folate-dependent metabolic pathways has been achieved through the use of antifolates. Unfortunately, the efficacy of many clinically approved antifolates is limited by a lack of tumor selectivity. Facilitative transport of folates into mammalian cells is achieved by the reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT). As PCFT is a folate-proton symporter with an acidic pH optimum, PCFT may provide a mechanism for targeting cytotoxic antifolates to tumors, based on their acidic microenvironments. To establish the …

Trends In The Utilization Of Outpatient Advanced Imaging After The Deficit Reduction Act., David C Levin, Vijay M Rao, Laurence Parker

Department of Radiology Faculty Papers

PURPOSE: After the Deficit Reduction Act (DRA) took effect in 2007, there was concern that private office-based imaging facilities would close, that advanced imaging would shift to less convenient hospital-based facilities, and that access to advanced imaging might be restricted. The aim of this study was to see if these developments occurred during the years after the DRA.

METHODS: Using Medicare data, outpatient CT, MRI, and nuclear medicine trends before and after the DRA were studied. Procedure volumes performed in private offices and hospital outpatient departments (HOPDs) were tabulated separately. Volumes were tracked from 2000 to 2006 (before the DRA) …

Hdm2 Small-Molecule Inhibitors For Therapeutic Intervention In B-Cell Lymphoma, Angela Sosin

Wayne State University Dissertations

Lymphomas frequently retain wild-type (wt) p53 function but overexpress HDM2, compromising p53 activity. Therefore, lymphoma is a suitable model for studying therapeutic value of disrupting HDM2-p53 association by small-molecule inhibitors (SMIs). HDM2 SMIs have been developed and are currently under various stages of preclinical and clinical investigation. This study examined various molecular mechanisms associated and biological effects of two different classes of HDM2 SMIs: the spiro-oxindoles (MI-219) and cis-imidazoline (Nutlin-3) in lymphoma cell lines and patient-derived B-lymphoma cells. Surprisingly, results revealed significant quantitative and qualitative differences between these two agents. At the molecular level, effect of Nutlin-3 was generally more …

Cost Effectiveness Of A Home-Based Intervention That Helps Functionally Vulnerable Older Adults Age In Place At Home., Eric Jutkowitz, Laura N Gitlin, Laura T. Pizzi, Edward Lee, Marie P Dennis

College of Population Health Faculty Papers

Evaluating cost effectiveness of interventions for aging in place is essential for adoption in service settings. We present the cost effectiveness of Advancing Better Living for Elders (ABLE), previously shown in a randomized trial to reduce functional difficulties and mortality in 319 community-dwelling elders. ABLE involved occupational and physical therapy sessions and home modifications to address client-identified functional difficulties, performance goals, and home safety. Incremental cost-effectiveness ratio (ICER), expressed as additional cost to bring about one additional year of life, was calculated. Two models were then developed to account for potential cost differences in implementing ABLE. Probabilistic sensitivity analyses were …

Accuracy Of Automated Attenuation-Based 3-Dimensional Segmentation: In The Analysis Of Left Ventricular Function Compared With Magnetic Resonance Imaging, Harald Brodoefel, Ilias Tsiflikas, Ulrich Kramer, Nina Lang, Anja Reimann, Christoph Burgstahler, Claus D Claussen, Martin Heuschmid

The Texas Heart Institute Journal

We evaluated attenuation-based 3-dimensional segmentation for the analysis of left ventricular function, using as our standard of reference magnetic resonance imaging and dual-source computed tomography with traditional short-axis planimetry.

Twenty patients with known or suspected coronary artery disease were examined prospectively. In all magnetic resonance and computed tomographic datasets, global functional values were determined by 2-dimensional planimetry. Computed tomographic scans were further evaluated by automated 3-dimensional segmentation, and the results were compared by Pearson correlation and Bland-Altman analysis.

Agreement between magnetic resonance imaging and dual-source computed tomographic 2-dimensional planimetry was good for all values (end-diastolic volume, bias= −4.2, r=0.99; end-systolic …

Species Identification Of Invasive Yeasts Including Candida In Pakistan: Limitations Of Phenotypic Methods, Joveria Farooqi, Kauser Jabeen, Noureen Saeed, Afia Zafar, Mary Eleanor Brandt, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objective: To compare phenotypic and genotypic methods of yeast identification. Methods: The in-vitro cross-sectional study was conducted from January 2006 to May 2009. Invasive yeasts isolated at the clinical microbiology laboratory at the Aga Khan University (AKU), Karachi, Pakistan, were identified. Speciation by phenotypic and molecular methods was compared. All yeasts isolated during the study period from blood and other invasive sites were identified using standard methods. Isolates were shipped to Mycotic Diseases Branch, Centres for Disease Control and Prevention, Atlanta, Georgia, USA, for identification by Luminex flow cytometric multianalyte profiling (xMAP) system. Ribosomal ITS2 DNA sequencing was performed …

Brain-Computer Interfaces In Medicine, Jerry J. Shih, Dean J. Krusienski, Johnathan R. Wolpaw

Electrical & Computer Engineering Faculty Publications

Brain-computer interfaces (BCIs) acquire brain signals, analyze them, and translate them into commands that are relayed to output devices that carry out desired actions. BCIs do not use normal neuromuscular output pathways. The main goal of BCI is to replace or restore useful function to people disabled by neuromuscular disorders such as amyotrophic lateral sclerosis, cerebral palsy, stroke, or spinal cord injury. From initial demonstrations of electroenceph-alography-based spelling and single-neuron-based device control, researchers have gone on to use electroenceph-alographic, intracortical, electrocorticographic, and other brain signals for increasingly complex control of cursors, robotic arms, prostheses, wheelchairs, and other devices. Brain-computer interfaces …

Macrophage Imbalance (M1 Vs. M2) And Upregulation Of Mast Cells In Wall Of Ruptured Human Cerebral Aneurysms: Preliminary Results., David Hasan, Nohra Chalouhi, Pascal Jabbour, Tomoki Hashimoto

Department of Neurosurgery Faculty Papers

BACKGROUND: M1 and M2 cells are two major subsets of human macrophages that exert opposite effects on the inflammatory response. This study aims to investigate the role of macrophage M1/M2 imbalance and mast cells in the progression of human cerebral aneurysms to rupture.

METHODS: Ten patients with cerebral aneurysms (five ruptured and five unruptured) underwent microsurgical clipping. During the procedure, a segment of the aneurysm dome was resected and immunostained with monoclonal antibodies for M1 cells (anti-HLA DR), M2 cells (anti-CD 163), and mast cells (anti-tryptase clone AA). A segment of the superficial temporal artery (STA) was also removed and …

Investigating The Impact Of Cd147 And Its Expression On Neurodegenaration And Alzheimer's Disease (Ad), Limbikani J. Kanyenda

Theses: Doctorates and Masters

CD147, also known as basigin, extracellular matrix metalloproteinase inducer, neurothelin, tumour cell-derived collagenase stimulatory factor, M6, HT7, OX47 or gp42, is a transmembrane glycoprotein of the immunoglobulin super-family. It is expressed in many neuronal and non-neuronal tissues with high expression in the hippocampus, pre-frontal cortex, thyroid, heart, early erythroid, amygdala and placenta. This protein is involved in various cellular and biological functions such as lymphocyte migration and maturation, tissue repair, cancer progression, T and B lymphocyte activation and induction of extracellular matrix metalloproteinase. The CD147 protein interacts with with cyclophilin A, cyclophilin B, sterol carrier protein, caveolin-1 and integrins, and …

The Effectiveness Of Airway Management In The Pre Hospital Treatment Of Traumatic Brain Injury : A Retrospective, Observational Study Of Pre Hospital Treatment Of Traumatic Brain Injury (Tbi) In The Western Australian Ambulance Service, Joseph Cuthbertson

Theses: Doctorates and Masters

There is concern over mortality and the potential for secondary brain injury in the head-injured patient. The use of advanced airway management and rapid sequence intubation in the pre hospital treatment of patients with Traumatic Brain Injury is controversial. Currently in St John Ambulance Service Australia (WA) Inc. three forms of pre hospital treatment are utilized to manage the airway of the adult head-injured patient. If attended by on-road paramedic staff, basic airway management is utilized unless the patient is unconscious and areflexic, in which case advanced airway management utilising endotracheal intubation or laryngeal mask insertion is authorised. In the …

Sindh Health Sector Strategy 2012 – 2020, Shehla Zaidi

Community Health Sciences

No abstract provided.

Spontaneous Coronary Artery Dissection: A Rare But Deadly Cause Of Acs In Younger Patients, Daniel J. Makowski Do, David A. Cox Md

Department of Medicine

No abstract provided.

High Isoniazid Resistance Rates In Rifampicin Susceptible Mycobacterium Tuberculosis Pulmonary Isolates From Pakistan, Naima Fasih, Yasraba Rafiq, Kausar Jabeen, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background:
Rapid new diagnostic methods (including Xpert MTB/RIF assay) use rifampicin resistance as a surrogate marker for multidrug resistant tuberculosis. Patients infected with rifampicin susceptible strains are prescribed first line anti-tuberculosis therapy. The roll out of such methods raises a concern that strains with resistance to other first line anti-tuberculosis drugs including isoniazid will be missed and inappropriate treatment given. To evaluate implications of using such methods review of resistance data from high burden settings such as ours is essential.
Objective:
To determine resistance to first line anti-tuberculosis drugs amongst rifampicin susceptible pulmonary Mycobacterium tuberculosis (MTB) isolates from Pakistan.
Material …

Functional Evaluation Of The Urinary Tract By Duplex Doppler Ultrasonography In Patients With Acute Renal Colic., Raza Sayani, Muhammad Ali, Kashif Shazlee, Rana Shoaib Hamid, Kamran Hamid

Department of Radiology

Purpose: To determine the role of duplex Doppler ultrasonography (DDU) in Patients with acute unilateral renal obstruction. Subjects And Methods:A total of 161 Patients with suspected renal colic due to urolithiasis were evaluated by DDU followed by intravenous urography (IVU). The mean intra-arterial resistive index (RI) and the difference of mean resistive index between both kidneys (delta RI) were determined for each person. An RI value of ≥0.70 and a delta RI value of ≥0.06 were taken as the discriminatory threshold for obstruction. IVU results were considered the " reference standard" against which renal DDU findings were compared.

Results: …

Factors Influencing The Opinion Of Individuals In Determining Tumour Spread After Biopsy, Tayyaba Z. Ansari, Adnan A. Zaidi, Asra Parekh, Owais Iqbal, Nehal Masood, Ahmed Mateen, Tehseen Fatima

Section of General Surgery

Background: People often have concerns regarding tumour spread after biopsy which leads to a delay in seeking expert medical advice. The data regarding this perception is scanty. Therefore, we conducted this cross sectional study to explore the beliefs and perceptions of individuals regarding tumour spread after biopsy and the basis of those beliefs.
Methods: The survey was conducted in outPatient areas of two different tertiary care hospitals of Karachi namely Aga Khan University Hospital Karachi (AKUH) and Karachi Institute of Radiotherapy and Nuclear Medicine (KIRAN). We interviewed 600 individuals and documented their responses on a questionnaire. There were 400 responders …

Microglial P38Α Mapk Is Critical For Lps-Induced Neuron Degeneration, Through A Mechanism Involving Tnfα, Bin Xing, Adam D. Bachstetter, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: The p38α MAPK isoform is a well-established therapeutic target in peripheral inflammatory diseases, but the importance of this kinase in pathological microglial activation and detrimental inflammation in CNS disorders is less well understood. To test the role of the p38α MAPK isoform in microglia-dependent neuron damage, we used primary microglia from wild-type (WT) or p38α MAPK conditional knockout (KO) mice in co-culture with WT cortical neurons, and measured neuron damage after LPS insult.

RESULTS: We found that neurons in co-culture with p38α-deficient microglia were protected against LPS-induced synaptic loss, neurite degeneration, and neuronal death. The involvement of the proinflammatory …

The Diagnosis Of Multiple Personality Disorder, Joshua D. Mcdavid, Md, Mph

Jefferson Journal of Psychiatry

This paper represents an attempt to facilitate the clinician or psychiatrist in making a diagnosis of Multiple Personality Disorder, the most severe of the dissociative disorders. Emphasis will be placed on detecting signs, symptoms, and information that occur within the constituent parts of a typical psychiatric interview, and that are highly suggestive of MPD even in the absence of alter presentation.

Psychogenic Amnesia: A Case Involving Amobarbital Interview And The News Media, Tracey G. Skale, Md, James Randolph Hillard, Md

Jefferson Journal of Psychiatry

A young man was admitted to an urban general hospital psychiatric unit after being brought from a local shopping mall unable to remember his name or any other personal information. He was alert and oriented and demonstrated no cognitive impairment. He agreed to an amobarbital interview and agreed to letting local news media display his picture in hopes that someone would recognize him. The amobarbital interview yielded information allowing identification of the individual, with the help of the news media. News media coverage also led to the discovery that the individual was wanted for a violent crime in another state …

Teachers’ And Parents’ Perspective As How The Social Environment Of Immediate Vicinity Can Affect The Academic Learning Of A Child 4-6 Years Age Group, Salma Amin Rattani, Deedar Shah

School of Nursing & Midwifery

In the process of human development environment plays a pivotal role. At the age of 4 -6 years, children's immediate vicinity expands from home to school and in his social environment parents and teachers play a vital role. Therefore, in this study which was conducted in Phander district Ghizer, Northern areas; of Pakistan, employing descriptive research design five parents and five school teachers were enrolled. Participants shared their definition and understanding about social environment and immediate vicinity and its effects on academic learning. This research is part of Advanced Diploma in Human Development: Early Child Development Programme, Aga Khan University. …

Patterns Of Information Behavior And Prostate Cancer Knowledge Among African-American Men, Levi Ross, Tyra Dark, Heather Orom, Willie Underwood Iii, Charkarra T. Anderson-Lewis, Jarrett Johnson, Deborah O. Erwin

Faculty Publications

The purposes of this study are to explore cancer information acquisition patterns among African-American men and to evaluate relationships between information acquisition patterns and prostate cancer prevention and control knowledge. A random sample of 268 men participated in a statewide interviewer-administered, telephone survey. Men classified as non-seekers, non-medical source seekers, and medical source seekers of prostate cancer information differed on household income, level of education, and beliefs about personal risk for developing prostate cancer. Results from multiple regression analysis indicated that age, education, and information-seeking status were associated with overall levels of prostate cancer knowledge. Results from logistic regression analyses …

Functional Genomics Reveals An Essential And Specific Role For Stat1 In Protection Of The Central Nervous System Following Herpes Simplex Virus Corneal Infection, Tracy J. Pasieka, Cristian Cilloniz, Victoria S. Carter, Pamela Rosato, Michael G. Katze, David A. Leib

Dartmouth Scholarship

Innate immune deficiencies result in a spectrum of severe clinical outcomes following infection. In particular, there is a strong association between loss of the signal transducer and activator of transcription (Stat) pathway, breach of the blood-brain barrier (BBB), and virus-induced neuropathology. The gene signatures that characterize resistance, disease, and mortality in the virus-infected nervous system have not been defined. Herpes simplex virus type 1 (HSV-1) is commonly associated with encephalitis in humans, and humans and mice lacking Stat1 display increased susceptibility to HSV central nervous system (CNS) infections. In this study, two HSV-1 strains were used, KOS (wild type [WT]), …

Evaluation Of The Pilot Program, Pediatric Early Warning Sentinel Surveillance Program (Pewss), And Its Efficacy In Monitoring Pediatric Illness In Clark County, Nevada, Michelle Lee Lutman

UNLV Theses, Dissertations, Professional Papers, and Capstones

The influenza outbreak that occurred during 2009 stimulated the formation of several surveillance programs throughout the country. The majority monitor only influenza; however, there are several other circulating respiratory pathogens, especially within the pediatric community. These other respiratory pathogens cause a variety of illnesses, such as bronchitis, pneumonia, croup, etc. Prior research has provided the medical community with valuable information about respiratory illnesses, especially those which afflict pediatric patients. Areas of knowledge including seasonality, demographics, signs and symptoms, prevention measures, and pathogenicity, have been greatly expanded over the years. This information has been of tremendous help to the medical community …

Association Between Childhood Demographics And Blood Lead Screening---Nevada Kindergarten Health Survey 2010, Lina Zhang

UNLV Theses, Dissertations, Professional Papers, and Capstones

Lead, as a toxic substance, invades the human body, and gradually damages the organs. Oftentimes, elevated blood lead levels are not recognized until serious health issues are found. In the United States, approximately 250,000 children aged 1-5 years have elevated blood lead levels greater than 10 micrograms of lead per deciliter of blood (Centers for Disease Control and Prevention, 2004).

However, there is no effective treatment for lead poisoning. Chelation can merely decrease the blood lead levels but cannot reverse the existing damage. To prevent and control childhood lead poisoning, many studies have been conducted to investigate the sources of …

Determining The Factors Associated With Unmet Need For Family Planning: A Cross-Sectional Survey In 49 Districts Of Pakistan, Waqas Hameed, Syed Khurram Azmat, Mohsina Bilgrami, Muhammad Ishaqe

Community Health Sciences

Introduction & Background: Around 137 million women in the developing world who would like to avoid childbearing are unable to do so, despite a huge increase in contraceptive access and use globally. Ironically, the prevalence of unmet need in Pakistan is among the highest in the world despite being one of the first countries in South Asia to launch national family planning program. The aim of this paper is to estimate the prevalence of unmet need for contraception and to indentify the factors associated with it.
Methods: A cross-sectional survey was conducted in forty nine districts of Pakistan across all …