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2011

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Articles 6541 - 6570 of 6767

Full-Text Articles in Medicine and Health Sciences

Unilateral Thalamic Infarction Presenting As Vertical Gaze Palsy: A Case Report, Muhib Khan, Christos Sidiropoulos, Panayiotis Mitsias Jan 2011

Unilateral Thalamic Infarction Presenting As Vertical Gaze Palsy: A Case Report, Muhib Khan, Christos Sidiropoulos, Panayiotis Mitsias

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

Vertical gaze palsy is a recognized manifestation of midbrain lesions. It rarely is a consequence of unilateral thalamic infarction.

Case presentation

We report the case of a 48-year-old African-American woman who presented to our facility with vertical gaze palsy and evidence of left medial thalamic infarct on diffusion-weighted imaging without coexisting midbrain ischemia. The etiology of infarct was determined to be small vessel disease after extensive investigation.

Conclusions

This report suggests a possible role of the thalamus as a vertical gaze control center. Clinicoradiological studies are needed to further define the role of the thalamus in vertical gaze …


Lack Of An Association Of Mir-938 Snp In Iddm10 With Human Type 1 Diabetes, Xiaofan Mi, Hongzhi He, Yangxin Deng, Abert M. Levin, Jin-Xiong She, Qing-Sheng Mi, Li Zhou Jan 2011

Lack Of An Association Of Mir-938 Snp In Iddm10 With Human Type 1 Diabetes, Xiaofan Mi, Hongzhi He, Yangxin Deng, Abert M. Levin, Jin-Xiong She, Qing-Sheng Mi, Li Zhou

Wayne State University Associated BioMed Central Scholarship

Abstract

MicroRNAs (miRNAs) are a newly discovered type of small non-protein coding RNA that function in the inhibition of effective mRNA translation, and may serve as susceptibility genes for various disease developments. The SNP rs12416605, located in human type 1 diabetes IDDM10 locus, changes the seeding sequence (UGU[G/A]CCC) of miRNA miR-938 and potentially alters miR-938 targets, including IL-16 and IL-17A. In an attempt to test whether miR-938 may be a susceptibility gene for IDDM10, we assessed the possible association of the miR-938 SNP with T1D in an American Caucasian cohort of 622 patients and 723 healthy controls by TaqMan assay. …


Inhibition Of Cathepsin B Activity Attenuates Extracellular Matrix Degradation And Inflammatory Breast Cancer Invasion, Bernadette C. Victor, Arulselvi Anbalagan, Mona M. Mohamed, Bonnie F. Sloane, Dora Cavallo-Medved Jan 2011

Inhibition Of Cathepsin B Activity Attenuates Extracellular Matrix Degradation And Inflammatory Breast Cancer Invasion, Bernadette C. Victor, Arulselvi Anbalagan, Mona M. Mohamed, Bonnie F. Sloane, Dora Cavallo-Medved

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

Inflammatory breast cancer (IBC) is an aggressive, metastatic and highly angiogenic form of locally advanced breast cancer with a relatively poor three-year survival rate. Breast cancer invasion has been linked to proteolytic activity at the tumor cell surface. Here we explored a role for active cathepsin B on the cell surface in the invasiveness of IBC.

Methods

We examined expression of the cysteine protease cathepsin B and the serine protease urokinase plasminogen activator (uPA), its receptor uPAR and caveolin-1 in two IBC cell lines: SUM149 and SUM190. We utilized a live cell proteolysis assay to localize in real …


Brain Candy: Wayne State University School Of Medicine Journal Of Art And Literature, 3rd Edition, Wayne State University School Of Medicine Writing Workshop, Wayne State University School Of Medicine Gold Humanism Honor Society Jan 2011

Brain Candy: Wayne State University School Of Medicine Journal Of Art And Literature, 3rd Edition, Wayne State University School Of Medicine Writing Workshop, Wayne State University School Of Medicine Gold Humanism Honor Society

Gold Humanism Honor Society

Brain Candy collects poetry, nonfiction essays, short fiction, photographs, and drawings to shed light on the creative process in medicine, the city of Detroit, and the experiences of health care providers. Features submissions from the School of Medicine (including the Writing Workshop), the WSU Department of English, and the WSU Department of Fine Arts. It also reintroduces the creative efforts of Detroit’s "Future Docs," children ages 6 through 12 with a curiosity for the field of medicine.


The Potential Role Of Innate Immunity In The Pathogenesis Of Post-Operative Adhesions, Jennell White Jan 2011

The Potential Role Of Innate Immunity In The Pathogenesis Of Post-Operative Adhesions, Jennell White

Wayne State University Dissertations

Post-operative adhesion development occurs in the vast majority of patients following abdominal surgery and is a natural occurrence of peritoneal-wound healing. These fibrous bands may form within the first 5-7 days post-surgery and have the ability to cause a distortion in the normal anatomical positioning of abdominal organs. Consequently, adhesions are major contributors to small bowel obstruction, infertility, and severe pelvic and abdominal pain. Physiological processes responsible for adhesion formation remain obscure though it is believed to involve cell migration, proliferation, and differentiation of several cell types including mesothelial cells, fibroblasts, and inflammatory and immune cells. Substances released from these …


Overuse Of Antibiotics In Children For Upper Respiratory Infections (Uris): A Dilemma, Malika Taufiq, Rukhsana Wamiq Zuberi Jan 2011

Overuse Of Antibiotics In Children For Upper Respiratory Infections (Uris): A Dilemma, Malika Taufiq, Rukhsana Wamiq Zuberi

Department for Educational Development

No abstract provided.


Consultation Etiquette In General Practice: A Qualitative Study Of What Makes It Different For Lay Cancer Caregivers, Geoffry K. Mitchell, Moyez Jiwa, Afaf Girgis Jan 2011

Consultation Etiquette In General Practice: A Qualitative Study Of What Makes It Different For Lay Cancer Caregivers, Geoffry K. Mitchell, Moyez Jiwa, Afaf Girgis

Medical Papers and Journal Articles

Background: It is commonplace for lay caregivers to overlook their own health concerns when supporting someone with advanced cancer. During this time, caregivers’ needs as patients are often marginalised by health professionals, including General Practitioners (GPs), who may miss the breadth of caregivers’ needs by focusing on the practicalities of caregiving. GPs traditionally rely on patients to raise their concerns, and then respond to these concerns, but caregivers as patients may be disinclined to cue their GP. The norms of engagement when caregivers consult their GP are less defined, and how they interact with their GP regarding their own health …


Opposing Actions Of Extracellular Signal-Regulated Kinase (Erk) And Signal Transducer And Activator Of Transcription 3 (Stat3) In Regulating Microtubule Stabilization During Cardiac Hypertrophy, D Ng, I Ng, B Badrian, T Tsoutsman, J Mcmullen, C Semsarian, M Bogoyevitch Jan 2011

Opposing Actions Of Extracellular Signal-Regulated Kinase (Erk) And Signal Transducer And Activator Of Transcription 3 (Stat3) In Regulating Microtubule Stabilization During Cardiac Hypertrophy, D Ng, I Ng, B Badrian, T Tsoutsman, J Mcmullen, C Semsarian, M Bogoyevitch

Medical Papers and Journal Articles

Excessive proliferation and stabilization of the microtubule (MT) array in cardiac myocytes can accompany pathological cardiac hypertrophy, but the molecular control of these changes remains poorly characterized. In this study, we examined MT stabilization in two independent murine models of heart failure and revealed increases in the levels of post-translationally modified stable MTs, which were closely associated with STAT3 activation. To explore the molecular signaling events contributing to control of the cardiac MT network, we stimulated cardiac myocytes with an a-adrenergic agonist phenylephrine (PE), and observed increased tubulin content without changes in detyrosinated (glutubulin) stable MT’s. In contrast, the hypertrophic …


Lifestyle And Demographic Correlates Of Poor Mental Health In Early Adolescence, Monique Robinson, Garth Kendall, Peter Jacoby, Beth P. Hands, Lawrence Beilin, Sven Silburn, Steve Zubrick, Wendy Oddy Jan 2011

Lifestyle And Demographic Correlates Of Poor Mental Health In Early Adolescence, Monique Robinson, Garth Kendall, Peter Jacoby, Beth P. Hands, Lawrence Beilin, Sven Silburn, Steve Zubrick, Wendy Oddy

Health Sciences Papers and Journal Articles

Aim: To determine the constellation of lifestyle and demographic factors that are associated with poor mental health in an adolescent population.

Methods: The Raine Study 14-year follow-up involved primary care givers and their adolescent children (n = 1860). The Child Behaviour Checklist (CBCL) was used to assess adolescent mental health. We examined diet, socio-demographic data, family functioning, physical activity, screen use and risk-taking behaviours with mental health outcomes using linear regression.

Results: Adolescents with higher intakes of meat and meat alternatives and ‘extras’ foods had poorer mental health status. Adverse socioeconomic conditions, higher hours of screen use and ever partaking …


Visualizing The Role Of Cbl-B In Control Of Islet-Reactive Cd4 T Cells And Susceptibility To Type 1 Diabetes, Gerard F. Hoyne, Eleanor Flening, Mehmet Yabas, Charis Teh, John A. Altin, Katrina Randall, Christine B F Thien, Wallace Y. Langdon, Christopher C. Goodnow Jan 2011

Visualizing The Role Of Cbl-B In Control Of Islet-Reactive Cd4 T Cells And Susceptibility To Type 1 Diabetes, Gerard F. Hoyne, Eleanor Flening, Mehmet Yabas, Charis Teh, John A. Altin, Katrina Randall, Christine B F Thien, Wallace Y. Langdon, Christopher C. Goodnow

Health Sciences Papers and Journal Articles

The E3 ubiquitin ligase Cbl-b regulates T cell activation thresholds and has been associated with protecting against Type 1 diabetes, but its in vivo role in the process of self-tolerance has not been examined at the level of potentially auto-aggressive CD4+ T cells. Here we visualize the consequences of Cbl-b deficiency on self-tolerance to lysozyme antigen expressed in transgenic mice under control of the insulin promoter (insHEL). By tracing the fate of pancreatic islet-reactive CD4+ T cells in pre-diabetic 3A9-TCR x insHEL double-transgenic mice, we find that Cbl-b deficiency contrasts with AIRE or IL-2 deficiency because it does not affect …


Association Of Retinoic Acid Receptor Genes With Meningomyelocele, Phong X Tran, Kit Sing Au, Alanna C Morrison, Jack M Fletcher, Kathryn K Ostermaier, Gayle H Tyerman, Hope Northrup Jan 2011

Association Of Retinoic Acid Receptor Genes With Meningomyelocele, Phong X Tran, Kit Sing Au, Alanna C Morrison, Jack M Fletcher, Kathryn K Ostermaier, Gayle H Tyerman, Hope Northrup

Faculty, Staff and Student Publications

BACKGROUND: Neural tube defects (NTDs) occur in as many as 0.5-2 per 1000 live births in the United States. One of the most common and severe neural tube defects is meningomyelocele (MM) resulting from failed closure of the caudal end of the neural tube. MM has been induced by retinoic acid teratogenicity in rodent models. We hypothesized that genetic variants influencing retinoic acid (RA) induction via retinoic acid receptors (RARs) may be associated with risk for MM.

METHODS: We analyzed 47 single nucleotide polymorphisms (SNPs) that span across the three retinoic acid receptor genes using the SNPlex genotyping platform. Our …


Immunopathology Of Postprimary Tuberculosis: Increased T-Regulatory Cells And Dec-205-Positive Foamy Macrophages In Cavitary Lesions, Kerry J Welsh, Semyon A Risin, Jeffrey K Actor, Robert L Hunter Jan 2011

Immunopathology Of Postprimary Tuberculosis: Increased T-Regulatory Cells And Dec-205-Positive Foamy Macrophages In Cavitary Lesions, Kerry J Welsh, Semyon A Risin, Jeffrey K Actor, Robert L Hunter

Faculty, Staff and Student Publications

Postprimary tuberculosis occurs in immunocompetent people infected with Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80% of cases and nearly 100% of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, lipid pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in lipid pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker …


Probing The Mechanical Properties Of Tnf-A Stimulated Endothelial Cell With Atomic Force Microscopy, Sei-Young Lee, Ana-Maria Zaske, Tommaso Novellino, Delia Danila, Mauro Ferrari, Jodie Conyers, Paolo Decuzzi Jan 2011

Probing The Mechanical Properties Of Tnf-A Stimulated Endothelial Cell With Atomic Force Microscopy, Sei-Young Lee, Ana-Maria Zaske, Tommaso Novellino, Delia Danila, Mauro Ferrari, Jodie Conyers, Paolo Decuzzi

Faculty, Staff and Student Publications

TNF-α (tumor necrosis factor-α) is a potent pro-inflammatory cytokine that regulates the permeability of blood and lymphatic vessels. The plasma concentration of TNF-α is elevated (> 1 pg/mL) in several pathologies, including rheumatoid arthritis, atherosclerosis, cancer, pre-eclampsia; in obese individuals; and in trauma patients. To test whether circulating TNF-α could induce similar alterations in different districts along the vascular system, three endothelial cell lines, namely HUVEC, HPMEC, and HCAEC, were characterized in terms of 1) mechanical properties, employing atomic force microscopy; 2) cytoskeletal organization, through fluorescence microscopy; and 3) membrane overexpression of adhesion molecules, employing ELISA and immunostaining. Upon stimulation …


Alterations In Content And Localization Of Defensins In Rat Ileum And Jejunum Following Ischemia-Reperfusion Specific Peptides, In Specific Places, For Specific Jobs?, Rosemary A Kozar, Rachel J Santora, Brian J Poindexter, Stephen M Milner, Roger J Bick Jan 2011

Alterations In Content And Localization Of Defensins In Rat Ileum And Jejunum Following Ischemia-Reperfusion Specific Peptides, In Specific Places, For Specific Jobs?, Rosemary A Kozar, Rachel J Santora, Brian J Poindexter, Stephen M Milner, Roger J Bick

Faculty, Staff and Student Publications

Objective: To determine alterations in quantities and distributions of natural antimicrobials following ischemia-reperfusion injury. We hypothesized that these compounds would be upregulated in areas of small intestine where changes in permeability and cellular disruption were likely and where protective mechanisms would be initiated. Methods: Rats with ischemia-reperfusion underwent superior mesenteric artery clamping and reperfusion. Shams were subjected to laparotomy but no clamping. Ileum and jejunum were harvested and sectioned, and subjected to fluorescence deconvolution microscopy for determinations of content and localization of rat beta defensins, 1, 2, 3; rat neutrophil protein-1; and cathelicidin LL-37. Modeling was performed to determine cellular …


Complete Genome Sequence Of Treponema Paraluiscuniculi, Strain Cuniculi A: The Loss Of Infectivity To Humans Is Associated With Genome Decay, David Smajs, Marie Zobaníková, Michal Strouhal, Darina Cejková, Shannon Dugan-Rocha, Petra Pospíšilová, Steven J Norris, Tom Albert, Xiang Qin, Kym Hallsworth-Pepin, Christian Buhay, Donna M Muzny, Lei Chen, Richard A Gibbs, George M Weinstock Jan 2011

Complete Genome Sequence Of Treponema Paraluiscuniculi, Strain Cuniculi A: The Loss Of Infectivity To Humans Is Associated With Genome Decay, David Smajs, Marie Zobaníková, Michal Strouhal, Darina Cejková, Shannon Dugan-Rocha, Petra Pospíšilová, Steven J Norris, Tom Albert, Xiang Qin, Kym Hallsworth-Pepin, Christian Buhay, Donna M Muzny, Lei Chen, Richard A Gibbs, George M Weinstock

Faculty, Staff and Student Publications

Treponema paraluiscuniculi is the causative agent of rabbit venereal spirochetosis. It is not infectious to humans, although its genome structure is very closely related to other pathogenic Treponema species including Treponema pallidum subspecies pallidum, the etiological agent of syphilis. In this study, the genome sequence of Treponema paraluiscuniculi, strain Cuniculi A, was determined by a combination of several high-throughput sequencing strategies. Whereas the overall size (1,133,390 bp), arrangement, and gene content of the Cuniculi A genome closely resembled those of the T. pallidum genome, the T. paraluiscuniculi genome contained a markedly higher number of pseudogenes and gene fragments (51). In …


Re: Sleep And The Family Doctor: Time To Lead, D. Bluestein, A. C. Healey, C. M. Rutledge Jan 2011

Re: Sleep And The Family Doctor: Time To Lead, D. Bluestein, A. C. Healey, C. M. Rutledge

Ellmer School of Nursing Faculty Publications

No abstract provided.


Educating Advanced Practice Nurses In Using Social Media In Rural Health Care, Carolyn M. Rutledge, Michelle Renaud, Laurel Shephard, Michele Bordelon, Tina Haney, Donna Gregory, Paula Ayers Jan 2011

Educating Advanced Practice Nurses In Using Social Media In Rural Health Care, Carolyn M. Rutledge, Michelle Renaud, Laurel Shephard, Michele Bordelon, Tina Haney, Donna Gregory, Paula Ayers

Ellmer School of Nursing Faculty Publications

Health care in the United States is facing a crisis in providing access to quality care for those in underserved and rural regions. Advanced practice nurses are at the forefront of addressing such issues, through modalities such as health care technology. Many nursing education programs are seeking strategies for better educating students on technology utilization. Health care technology includes electronic health records, telemedicine, and clinical decision support systems. However, little focus has been placed on the role of social media in health care. This paper describes an educational workshop using standardized patients and hands-on experiences to introduce advanced practice nurses …


Educating Advanced Practice Nurses In Using Social Media In Rural Health Care, Carolyn M. Rutledge, Michelle Renaud, Laurel Shepherd, Michele Bordelon, Tina Haney, Donna Gregory, Paula Ayers Jan 2011

Educating Advanced Practice Nurses In Using Social Media In Rural Health Care, Carolyn M. Rutledge, Michelle Renaud, Laurel Shepherd, Michele Bordelon, Tina Haney, Donna Gregory, Paula Ayers

Ellmer School of Nursing Faculty Publications

Health care in the United States is facing a crisis in providing access to quality care for those in underserved and rural regions. Advanced practice nurses are at the forefront of addressing such issues, through modalities such as health care technology. Many nursing education programs are seeking strategies for better educating students on technology utilization. Health care technology includes electronic health records, telemedicine, and clinical decision support systems. However, little focus has been placed on the role of social media in health care. This paper describes an educational workshop using standardized patients and hands-on experiences to introduce advanced practice nurses …


Coping Strategies Of Family Members Of Hospitalized Psychiatric Patients, Phyllis M. Eaton, Bertha L. Davis, Pamela V. Hammond, Esther H. Condon, Zina T. Mcgee Jan 2011

Coping Strategies Of Family Members Of Hospitalized Psychiatric Patients, Phyllis M. Eaton, Bertha L. Davis, Pamela V. Hammond, Esther H. Condon, Zina T. Mcgee

Ellmer School of Nursing Faculty Publications

This exploratory research paper investigated the coping strategies of families of hospitalized psychiatric patients and identified their positive and negative coping strategies. In this paper, the coping strategies of 45 family members were examined using a descriptive, correlational, mixed method research approach. Guided by the Neuman Systems Model and using the Family Crisis Oriented Personal Evaluation Scales and semistructured interviews, this paper found that these family members used more emotion-focused coping strategies than problem-focused coping strategies. The common coping strategies used by family members were communicating with immediate family, acceptance of their situation, passive appraisal, avoidance, and spirituality. The …


An Optimisation-Based Framework For Complex Business Process: Healthcare Application, Waleed Abo Hamad Jan 2011

An Optimisation-Based Framework For Complex Business Process: Healthcare Application, Waleed Abo Hamad

Doctoral

The Irish healthcare system is currently facing major pressures due to rising demand, caused by population growth, ageing and high expectations of service quality. This pressure on the Irish healthcare system creates a need for support from research institutions in dealing with decision areas such as resource allocation and performance measurement. While approaches such as modelling, simulation, multi-criteria decision analysis, performance management, and optimisation can – when applied skilfully – improve healthcare performance, they represent just one part of the solution. Accordingly, to achieve significant and sustainable performance, this research aims to develop a practical, yet effective, optimisation-based framework for …


Addressing The Fertility Needs Of Hiv-Seropositive Males, Brian A. Levine, Sahadat K. Nurudeen, Jennifer T. Gosselin, Mark V. Sauer Jan 2011

Addressing The Fertility Needs Of Hiv-Seropositive Males, Brian A. Levine, Sahadat K. Nurudeen, Jennifer T. Gosselin, Mark V. Sauer

Psychology Faculty Publications

An increasing number of serodiscordant couples are utilizing advanced reproductive technologies to address their reproductive needs. Recent literature has demonstrated that it is not only technically possible but also safe to utilize sperm-washing techniques to allow for the creation of embryos, thereby preventing both horizontal and vertical transmission of HIV. This article addresses the strengths and weakness of various reproductive techniques and discusses our experience at Columbia University (NY, USA), the location of the largest HIV-focused fertility program in the USA.


Measuring The Symptom Burden Of Lung Cancer: The Validity And Utility Of The Lung Cancer Module Of The M D Anderson Symptom Inventory, Tito R Mendoza, Xin Shelley Wang, Charles Lu, Guadalupe R Palos, Zhongxing Liao, Gary M Mobley, Shitij Kapoor, Charles S Cleeland Jan 2011

Measuring The Symptom Burden Of Lung Cancer: The Validity And Utility Of The Lung Cancer Module Of The M D Anderson Symptom Inventory, Tito R Mendoza, Xin Shelley Wang, Charles Lu, Guadalupe R Palos, Zhongxing Liao, Gary M Mobley, Shitij Kapoor, Charles S Cleeland

Faculty, Staff and Student Publications

We conducted a study to establish the psychometric properties of a module of the M. D. Anderson Symptom Inventory (MDASI) developed specifically for patients with lung cancer (MDASI-LC). The MDASI measures 13 common "core" symptoms of cancer and its treatment. The MDASI-LC includes the 13 core MDASI symptom items and three lung cancer-specific items: coughing, constipation, and sore throat. MDASI-LC items were administered to three cohorts of patients with lung cancer undergoing either chemotherapy or chemoradiotherapy. Known-group validity and criterion (concurrent) validity of the MDASI-LC were evaluated using the Eastern Cooperative Oncology Group performance status and the 12-item Short-Form Health …


Analysis Of Heel Raise Exercise With Three Foot Positions, Kimberly J. Arnsdorff, G. Ken Limbaugh, Bryan L. Riemann Jan 2011

Analysis Of Heel Raise Exercise With Three Foot Positions, Kimberly J. Arnsdorff, G. Ken Limbaugh, Bryan L. Riemann

Health Sciences & Kinesiology: Faculty Publications

Prior research revealed activation differences between the medial (MG) and lateral (LG) gastrocnemius when performing heel raise exercise with neutral (N), internally-rotated (IR) and externally-rotated (ER) foot positions. Studying underlying biomechanics may help explain activation differences. The purpose was to compare ankle (AN), knee (KN), and hip (HI) contributions (initial joint angles) to attaining each initial foot position, ankle flexion-extension range of motion, ankle mechanical energy expenditure, repetition time, and percent cycle concentric-eccentric transition between N, IR, and ER foot positions. Twenty healthy subjects (11 male, 9 female) with resistance training experience performed twelve repetitions of free-weight (135% body mass) …


Hindfoot And Forefoot Kinematic Differences Among Individuals With And Without Functional Ankle Instability, Cynthia Wright Jan 2011

Hindfoot And Forefoot Kinematic Differences Among Individuals With And Without Functional Ankle Instability, Cynthia Wright

Theses and Dissertations

Introduction: Following lateral ankle sprain, many individuals experience recurrent injury and symptoms of giving-way, known as Functional Ankle Instability (FAI). It has been proposed that altered joint kinematics during activity may contribute to instability in these individuals, however research findings have been inconsistent. Objective: To capture foot and ankle kinematic data during two common tasks (walking gait and jump landing) among three groups: individuals with FAI, healthy controls and copers. Design: 3-group observational cross-sectional study. Participants: Participants included 23 individuals with a history of ≥ 1 ankle sprain and at least 2 episodes of giving-way in the past year (FAI: …


Biochemical Evaluation Of Lignin-Like Molecules, Jay Thakkar Jan 2011

Biochemical Evaluation Of Lignin-Like Molecules, Jay Thakkar

Theses and Dissertations

Current anticoagulants carry a serious risk of bleeding complications. In addition, narrow therapeutic index, drug interactions, immunological reactions, toxicity and high cost to benefit ratio limits the effective use of these drugs in patients with thrombotic conditions.Heparin is the most widely used anticoagulant. We hypothesized that one of the major drawback of heparins, its non-specific interaction with the plasma proteins arises as a result of negative charges. To reduce these non-specific interactions, our laboratory designed sulfated low molecular weight lignin (LMWL) like biomacromolecules, which were found to be direct inhibitors of thrombin and factor Xa, acting through a unique exosite-2 …


“Clicked” Bivalent Multifunctional Ligands In Alzheimer’S Disease., Ronak Gandhi Jan 2011

“Clicked” Bivalent Multifunctional Ligands In Alzheimer’S Disease., Ronak Gandhi

Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by beta-amyloid (Aβ) aggregation/oligomerization, biometal dyshomeostasis, oxidative stress, and neuroinflammation. The multifactorial nature of AD may indicate the therapeutic potential of multifunctional ligands that tackle various risk factors simultaneously as effective AD-modifying agents. This notion is further supported by the fact that while numerous AD-modifying agents targeting one single risk factor have been developed and a number of them entered clinical trials, none of them has been successfully approved by the FDA. Furthermore, neuronal cell membrane/lipid rafts (CM/LR) have been demonstrated to associate with all the indicated risk factors, indicating that this …


Approaches For Enhancing Therapeutic Efficacy Of A Novel Il-10 Gene Family Member: Mda-7/Il-24, Belal Azab Jan 2011

Approaches For Enhancing Therapeutic Efficacy Of A Novel Il-10 Gene Family Member: Mda-7/Il-24, Belal Azab

Theses and Dissertations

Melanoma differentiation associated gene-7 (mda-7) was discovered in the Fisher laboratory by subtraction hybridization of temporally spaced subtracted cDNA libraries prepared from terminally differentiated human melanoma cells treated with human fibroblast interferon (IFN-β) and the protein kinase C activator mezerein (MEZ), an approach called ‘differentiation induction subtraction hybridization’ (DISH). mda-7 is located in human chromosome 1q32–33 and based on sequence homology, chromosomal localization, and its functional properties, the mda-7 gene is now classified as a member of the IL-10 family of cytokines and named IL-24. The mda-7/IL-24 cDNA encodes a protein of 206-amino acids with a predicted size of ~24-kDa, …


Cyclic-Di-Gmp Signaling In The Borrelia Spirochetes, John Freedman Jan 2011

Cyclic-Di-Gmp Signaling In The Borrelia Spirochetes, John Freedman

Theses and Dissertations

Lyme disease is the most common tick-borne disease in North America, with approximately 35,000 cases reported to the Centers for Disease Control in 2008. The genome of its causative agent, Borrelia burgdorferi, encodes for a set of genes involved in the metabolism and regulatory activities of the second messenger nucleotide, cyclic-di-GMP (c-di-GMP). Rrp1 is a response regulatory-diguanylate cyclase, and its regulatory capability is likely mediated via production of c-di-GMP, as it lacks a DNA-binding domain. One known class of c-di-GMP effector/binding proteins are those that harbor a PIlZ domain. The genome of B. burgdorferi strain 5A4 encodes for one chromosomally-carried …


Functional Consequences Of Cytosine Methylation In Mitochondrial Dna Catalyzed By Dna Methyltransferase 1, Lisa Shock Jan 2011

Functional Consequences Of Cytosine Methylation In Mitochondrial Dna Catalyzed By Dna Methyltransferase 1, Lisa Shock

Theses and Dissertations

Cytosine methylation of mitochondrial DNA (mtDNA) was first described several decades ago, but neither the mechanism generating this modification nor its functional significance was known. Because mitochondrial dysfunction is a hallmark characteristic of numerous human diseases, including neurological and cardiovascular disease, aging and cancer, this dissertation addressed whether epigenetic modification of mtDNA regulates mitochondrial function. We show that mtDNA contains not only 5-methylcytosine (5mC), but also 5-hydroxymethylcytosine (5hmC), suggesting that previous reports likely underestimated the degree of epigenetic modification within the mitochondrial genome. We questioned how these modifications were generated by looking for mitochondrial isoforms of the nuclear-encoded DNA methyltransferases. …


Genetic Manipulation Of The Relapsing Fever Spirochete Borrelia Hermsii Permits Novel Investigation Into The Role Of Factor H Binding In Borrelial Virulence, Lindy Fine Jan 2011

Genetic Manipulation Of The Relapsing Fever Spirochete Borrelia Hermsii Permits Novel Investigation Into The Role Of Factor H Binding In Borrelial Virulence, Lindy Fine

Theses and Dissertations

Borrelia hermsii, an etiologic agent of tick-borne relapsing fever, binds negative complement regulator factor H (FH) via its FhbA protein. Direct demonstration of the role of FhbA in the disease process has been hindered by the lack of genetic manipulation systems for the relapsing fever Borrelia. Here, we demonstrate successful generation of a B. hermsii strain YOR fhbA deletion mutant (Bh YORΔfhbA) that constitutively produces green fluorescent protein (GFP). Genetic manipulation did not affect growth rate or plasmid composition. Bh YORΔfhbA lost factor H-binding and C3b-inactivation capabilities, but retained resistance to killing in human serum and infectivity in mice. Stable …