Medicine and Health Sciences Commons^™

C-Abl And Arg Drive Cancer Chemoresistance Via Activation Of Multiple Signaling Pathways, Jonathan Thomas Sims

Theses and Dissertations--Pharmacology and Nutritional Sciences

Despite 35 years of clinical trials, there has been little improvement in one-year survival rates with any chemotherapeutic regimen for the treatment of metastatic melanoma due to resistance to all known agents. Regardless of advances in detection and prevention, diagnosis of metastatic disease remains a death sentence. Resistance mechanisms, including aberrant kinase signaling and drug transport pumps, indicate a need for identification of other therapeutic targets that impinge upon multiple signaling pathways. The Abl family of non-receptor tyrosine kinases (c-Abl, Arg) has been indicted as a causative force in leukemia for more than three decades; however, their role in solid …

Inflammatory Interactions And Secretion In Cardiac Remodeling, Fanmuyi Yang

Theses and Dissertations--Physiology

Heart failure contributes to nearly 60,000 deaths per year in the USA and is often caused by hypertension and preceded by the development of left ventricular hypertrophy (LVH). LVH is usually accompanied by intensive interstitial and perivascular fibrosis which may contribute to arrhythmogenic sudden cardiac death. Emerging evidence indicates that LV dysfunction in patients and animal models of cardiac hypertrophy is closely associated with perivascular inflammation.

To investigate the role of perivascular inflammation in coronary artery remodeling and cardiac fibrosis during hypertrophic ventricular remodeling, we used a well-established mouse model of pressure-overload-induced LVH: transverse aortic constriction (TAC). Early perivascular inflammation …

Reconstruction Of Nigrostriatal Pathway In An Animal Model Of Parkinson's Disease, Chen Zhang

Theses and Dissertations--Physiology

Parkinson's disease is characterized by progressive degeneration of substantia nigra (SN) and subsequently loss of the nigrostriatal circuit. Many strategies have attempted to reconstruct this circuit but failed to satisfy clinical trials. The inhibitory environment of the adult CNS and the long distance between the SN and the striatum make true reconstruction difficult. To reconstruct this circuit, we used a transplant-pathway targeting model. Several putative pathway targeting molecules were examined for their ability to direct the growth of axons from a dopaminergic transplant. For a proof-of-principle study, adenoviral and lentiviral encoded glial cell line-derived neurotrophic factor (GDNF), GDNF-receptor alpha1 (GFRa1 …

Synthesis And Flame Retardant Testing Of New Boronated And Phosphonated Aromatic Compounds, Vladimir Benin, Sravanthi Durganala, Alexander Morgan

Chemistry Faculty Publications

The present report describes the preparation and use of some dimethyl terephthalate derivatives in transition metal-catalyzed coupling reactions to produce new reactive flame retardants. Dimethyl iodoterephthalate and dimethyl 2,5-diiodoterephthalate were successfully employed in the preparation of phosphonic and boronic esters and acids. The latter were tested for heat release with a microcombustion calorimeter (ASTM D7309) to determine the potential for heat release reduction of these flame retardant molecules. The results showed that the addition of boronic or phosphonic acids greatly lowered the heat release, due to a condensed phase (char formation) mechanism. Adding ester groups to the boronic acids or …

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

Bioelectrics Publications

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

Linear Psoriasis Of The Isolated Type, Tatyana Groysman Do, Marc W. Levin Md

Department of Medicine

No abstract provided.

Malpositioned Pacemaker Lead Presenting As A Peculiar 12-Lead Ekg, Amit Nanavati Md, Robert F. Malacoff Md, Facc

Department of Medicine

No abstract provided.

A Proposal To Test The Effects Of Factor Ecat1 On Pluripotency, From Reprogramming To Differentiation Of Human Somatic Cells, Vritti R. Goel

CMC Senior Theses

The field of stem cell research has been growing more because of the interest in using stem cells to cure diseases and heal injuries. Human embryonic stem cells, because of the controversy surrounding them—and subsequently the difficulties in acquiring samples of the existing aging cell lines—can only be used in limited capacities. While the development of induced pluripotent stem cells in the last decade has allowed the field to progress closer to medical treatments, the low efficiency of reprogramming a somatic cell to a pluripotent state, and the vast molecular and genomic differences between human embryonic stem cells and human …

Characterization Of A Hyperthermophilic Redox Protein, Rubredoxin, As A Potential Targeted Cancer Therapeutic, Siri Lakshmi Chirumamilla

PCOM Biomedical Studies Student Scholarship

Cancer is an elusive neoplastic disease that claims the lives of many people around the world every year. Though treatments have become more specific to the different types of cancer, the need remains for antineoplastic drugs that target cancer cells and leave normal cells unharmed, with little to no systemic toxicity. The search for a targeted cancer therapeutic is necessary and urgent, and Pyrococcus furiosus rubredoxin might be such a tool. Rubredoxin is a small (53 amino acids), water soluble, non-heme iron electron transfer protein that contains an iron atom cofactor bound by the sulfurs of four cysteine residues, which …

The Factors Affecting Noninvasive Mechanical Ventilation Failure In Copd Exacerbations, Feza Bacakoğlu, Mehmet Sezai̇ Taşbakan, Özen Kaçmaz Başoğlu, Adnan Tolga Öz, Sedat Ürkmez, Meltem Mi̇di̇lli̇, Pervi̇n Korkmaz Ekren, Alev Gürgün

Turkish Journal of Medical Sciences

To evaluate causes of noninvasive mechanical ventilation (NIMV) failure. The rate of NIMV failure in respiratory failure due to chronic obstructive pulmonary disease (COPD) exacerbations was reported as 5%-40%. Materials and methods: The necessity of endotracheal intubation was accepted as NIMV failure. The causes of NIMV failure were assessed in 54 patients (45 males; mean age: 67.7 ± 11.0 years) treated with NIMV because of COPD exacerbations and respiratory failure in an intensive care unit (ICU). Results: There was NIMV failure in 20 patients (37.0%). The rates of hospital-acquired pneumonia and in-hospital mortality were higher (P = 0.003 and P …

Effects Of Phenolic Acids On Gastrointestinal Smooth Muscle Complications In Streptozotocine-Induced Diabetic Rats, Nurcan Bektaş, Yusuf Öztürk

Turkish Journal of Medical Sciences

To identify the effects of antioxidants on gastrointestinal smooth muscle complications in 6-week streptozotocine (STZ)-induced diabetic rats. Materials and methods: The following steps were carried out: 1. Three weeks after STZ injection, saline and 10 mg/kg p-OH benzoic, protocatechic, and gallic acids were separately administered to the rat groups every day for 3 weeks. 2. The responses of the fundus and ileum to agonists were recorded using isolated organ bath experiments. Results: Diabetic smooth muscle complications developed in the diabetic rats. The responses of the ileum to acetylcholine increased whereas the responses of the fundus to serotonine decreased in the …

A Rare Presentation Of Brucellosis: Polyradiculopathy And Peripheral Neuritis, Günay Ertem, Gülni̇hal Kutlu, Çi̇ğdem Ataman Hati̇poğlu, Cemal Bulut, Ali̇ Pekcan Demi̇röz

Turkish Journal of Medical Sciences

To present 8 patients with polyradiculopathy or polyradiculoneuritis caused by brucellosis. Polyradiculopathy or polyradiculoneuritis are occasional neurological involvements of brucellosis. Materials and methods: The diagnosis was made with clinical, serological and/or cerebrospinal fluid, and electromyographic examinations. Results: All of the patients except one improved quickly after specific antimicrobial treatment. Furthermore, electrophysiological examinations revealed normal findings in 6 patients. Conclusion: This clinical form of brucellosis is mostly reversible if it is diagnosed earlier and treated effectively.

Laboratory Criteria For Severe Crimean-Congo Haemorrhagic Fever : Letter To The Editor, Mesut Ortatatli, Serdar Ümi̇t Sarici

Turkish Journal of Medical Sciences

No abstract provided.

Effects Of Long-Term Passive Smoking On The Vascular Endothelial Growth Factor And Apoptosis Marker Expression In The Retina And Choroid: An Experimental Study, Sema Dündar, Fati̇h Özcura, İbrahi̇m Meteoğlu, Mehmet Erkut Kara

Turkish Journal of Medical Sciences

To investigate the effects of smoking, reported as a risk factor for age related macular degeneration (ARMD), on the vascular endothelial growth factor (VEGF) expression and apoptosis in the retina and choroid of rats. Materials and methods: This experimental study included 38 Sprague-Dawley rats. The rats were randomly assigned into 4 groups. Groups 1 (males) and 2 (females) were exposed to smoke beginning on day 21 after birth, whereas groups 3 (males) and 4 (females) were not exposed to smoke. At the end of the fourth month, the right eyes of all of the rats were enucleated. Immunohistochemical analysis was …

Risk Factors And Prognosis In Children Hospitalized Due To Pandemic H1n1 Influenza A Virus Infection In Ankara, Turkey*, Medi̇ne Ayşi̇n Taşar, Yildiz Bi̇lge, Özge Uysal Soyer, Şükran Yildirim, Mustafa Taşar, Fatma İnci̇ Arikan

Turkish Journal of Medical Sciences

To describe the demographic characteristics and clinical features in children with influenza A (H1N1) virus infection and to identify risk factors for severe disease or poor prognosis. Following the first tourist-imported case in Turkey on 16 May 2009, the influenza A (H1N1) virus has spread throughout the country. Materials and methods: Children under 18 years of age who were hospitalized for at least 24 h with an influenza-like illness and who had confirmed influenza A (H1N1) virus infection were included in the study. Demographic factors, clinical signs and symptoms, laboratory results, radiographic findings, treatments, and follow-up periods were noted. Results: …

Comparison Between Intravenous And Thoracic Epidural Analgesia In Single Coronary Artery Bypass Graft Surgery, Nevri̇ye Salman, Fati̇h Tanzer Serter, Hali̇l İbrahi̇m Uçar, Serdar Günaydin, Ali̇ Cem Yorgancioğlu

Turkish Journal of Medical Sciences

Aim: To compare thoracic epidural analgesia with intravenous analgesia in patients who underwent coronary artery bypass grafting surgery. Materials and methods: This retrospective study included 40 patients who had received elective single artery bypass surgery. After general anesthesia, one group was given patient-controlled thoracic epidural analgesia and the other group was given patient-controlled intravenous meperidine analgesia. Patient assessments were performed during the postoperative period and included the duration of hospital stay, pain and sedation scores, ambulation score, atrial fibrillation incidence, and organ morbidities. Results: No differences were detected between the groups in the demographic or intraoperative data. However, a statistically …

Iodine Deficiency In Pregnancy And In Women Of Reproductive Age In Erzurum, Turkey, Kadi̇r Çeti̇nkaya, Meti̇n İngeç, Semra Çeti̇nkaya, İbrahi̇m Kaplan

Turkish Journal of Medical Sciences

Aim: Iodine deficiency (ID) is an important public health problem and the most common cause of preventable mental retardation. The aims of this study were to determine the urinary iodine concentration (UIC) of pregnant women living in Erzurum, to assess the ID rate, and to find out whether iodine supplementation is necessary in pregnancy. Materials and methods: Spot urine was obtained from pregnant and nonpregnant women with no functional or organic thyroid disease. The UIC was studied using the Sandell-Kolthoff method. Results: The median UIC values of pregnant women in the first, second, and third trimesters and of the nonpregnant …

Serum Interleukin-8 Levels May Predict Relapse In Brucellosis, Nazlim Aktuğ Demi̇r, Onur Ural

Turkish Journal of Medical Sciences

To investigate whether cytokines are effective in predicting relapses among patients with acute brucellosis. Materials and methods: This trial was conducted in 42 patients who were being followed-up with diagnosis of acute brucellosis. Serum samples were obtained on days 0 and 45. In patients whose clinical symptoms recurred within a year of treatment and exhibited infectious parameters in compliance with brucellosis, a Rivanol standard tube agglutination (STA) test was performed and the diagnosis of relapse was based on brucella immunoglobulin M (IgM). Serum samples were evaluated for various parameters, namely tumor necrosis factor-alpha (TNF-\alpha), interferon-gamma (IFN-\gamma), interleukin 2 (IL-2), IL-4, …

The Esr1 Gene Polymorphisms In Patients With Coronary Artery Disease In The Southeastern Turkish Population, Abdussemet Hazar, Fuat Di̇lmeç, Aydemi̇r Koçarslan, Mustafa Göz, Mehmet Sali̇h Aydin, Abbas Heval Demi̇rkol

Turkish Journal of Medical Sciences

The objective of this study was to evaluate the prevalence of the estrogen receptor 1 (ESR1) gene variants and their possible association with coronary artery disease (CAD) in Şanlıurfa province. Materials and methods: We used polymerase chain reaction and restriction enzyme digestion to determine the prevalence of the ESR1 gene (NM_001122742.1, GI: 2099): c.454-351 A>G (XbaI A>G) and c.454-397 T>C (PvuII T>C) polymorphisms in 100 healthy individuals and 80 angiographically confirmed CAD patients. Results: The body mass index (28.1 ± 5.4), low-density lipoprotein cholesterol (126.1 ± 42 mg/dL), diabetes (n = 13), and hypertension (n = …

Effect Of Dietary Β-Sitosterol On Fecal Bacterial And Colonic Biotransformation Enzymes In 1,2-Dimethylhydrazine–Induced Colon Carcinogenesis, Albert Baskar Arul, Khalid Al Numair, Mohammed Al Saif, Ignacimuthu Savarimuthu

Turkish Journal of Medical Sciences

The present study was designed to investigate the modulatory effect of \beta-sitosterol administration on 1,2-dimethylhydrazine (DMH)-induced fecal bacterial and colonic biotransformation enzyme activities. Materials and methods: The chemopreventive potential of \beta-sitosterol in colon carcinogenesis was assessed by injecting DMH (20 mg/kg body weight) subcutaneously into male Wistar rats and supplementing with \beta-sitosterol throughout the experimental period of 16 weeks at 3 different doses (5, 10, and 20 mg/kg body weight). Results: Amplified activities of fecal bacterial (\beta-glucuronidase, \beta-glucosidase, \beta-galactosidase, nitroreductase, hyaluronate lyase, and sulfatase) and colonic biotransformation (\beta-glucuronidase, \beta-glucosidase, \beta-galactosidase, and nitroreductase) enzymes were considered hallmarks of colon carcinogenesis. DMH-induced …

Urothelial Cancers: Clinical And Imaging Evaluation, Hali̇l Arslan, Fati̇h Mehmet Tezcan, Oktay Alğin

Turkish Journal of Medical Sciences

Urothelial cancers are currently diagnosed more commonly parallel to the recent developments in imaging techniques. Early diagnosis of these tumors, together with better treatment options, decreases the morbidity and the mortality significantly. This review aims to summarize the imaging findings of urothelial tumors, both at the pretreatment and posttreatment follow-up stage.

Transdiaphragmatic Approach To Liver And Lung Hydatid Cysts, Yener Aydin, Mi̇ne Çeli̇k, Ali̇ Bi̇lal Ulaş, Ati̇la Eroğlu

Turkish Journal of Medical Sciences

Hydatid cysts are a clinical problem in developing and nondeveloped countries. This study aimed to present lung and liver hydatid cysts that underwent the transdiaphragmatic surgical approach. Materials and methods: The study retrospectively evaluated 50 consecutive patients with lung and liver hydatid cysts who underwent transdiaphragmatic surgical treatment at the authors' clinic between January 1998 and December 2011. Results: Twenty-four (48%) patients were male and 26 (52%) were female. The average age of the patients was 34 ± 21 (3-72). All patients had liver cysts and 37 had lung cysts. Forty-eight of the patients underwent thoracotomies, 1 a laparotomy, and …

Effects Of Long-Acting Beta-2 Agonist Treatment On Daily Energy Balance And Body Composition In Patients With Chronic Obstructive Pulmonary Disease, Abdurrahman Genç, Kağan Üçok, Ersi̇n Günay, Yücel Gönül, Hati̇ce Karabacak, Ümi̇t Şener, Serkan Nural, Mehmet Ünlü

Turkish Journal of Medical Sciences

The aim of this study was to investigate the effects of long-acting beta-2 agonist (formoterol) treatment on the resting metabolic rate (RMR), daily physical activity, body composition and anthropometry, nutritional status, and quality of life of patients with chronic obstructive pulmonary disease (COPD). Materials and methods: A total of 30 male patients who were diagnosed with COPD participated in the study. The RMR was determined using an indirect calorimeter, daily physical activity was measured with an accelerometer, and body composition was established by bioelectric impedance analysis. Body circumference and skinfold thickness measurements were carried out. Pulmonary function tests were performed …

Community Cancer Services, Clinical Trials, And Quality Initiatives--Year 2 Ncccp At Lehigh Valley Health Network, Ada M. Rivera Ba, Lenore A. Mcgonigle Ms, Maryellen Shiels Bs, Smiyyah Q. Whitney Rn, Suresh G. Nair Md, Janelle M. Sharma, Kathy Sevedge Rn, Ma, Aocn, Eliot L. Friedman Md, Nadesda Mack Rn, Bsn, Mba, Ocn, Gregory R. Harper Md, Phd

Department of Medicine

No abstract provided.

Ethanol Interactions With Dl-Methylphenidate Versus D-Methylphenidate In Humans, Owen Reeves

MUSC Theses and Dissertations

Adult Attention-Deficit/Hyperactivity Disorder (ADHD) affects~ 4.4% of the adult population, and patients with this disorder frequently have comorbid substance abuse disorders. Methylphenidate (MPH) is considered a first line pharmacotherapy agent in the treatment of ADHD, and is commonly used or co-abused with alcohol. Hydrolysis of oral racemic methylphenidate (dl-MPH) by carboxylesterase 1 (CES1) limits the bioavailability of the pharmacologically active d-MPH isomer to approximately 30% and that of the inactive 1-MPH isomer to only 1-2%. Co-administration of dl-MPH with ethanol results in elevated d-MPH plasma concentrations, as well as CES1 mediated enantioselective transesterification of 1-MPH to 1-ethylphenidate (EPH). The present …

Attenuation Of Corneal Myofibroblast Development Through Nanoparticle-Mediated Soluble Transforming Growth Factor-Β Type Ii Receptor (Stgfβrii) Gene Transfer, Ajay Sharma, Jason T. Rodier, Ashish Tandon, Alexander M. Klibanov, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: To explore (i) the potential of polyethylenimine (PEI)-DNA nanoparticles as a vector for delivering genes into human corneal fibroblasts, and (ii) whether the nanoparticle-mediated soluble extracellular domain of the transforming growth factor–β type II receptor (sTGFβRII) gene therapy could be used to reduce myofibroblasts and fibrosis in the cornea using an in vitro model.

Methods: PEI-DNA nanoparticles were prepared at a nitrogen-to-phosphate ratio of 30 by mixing linear PEI and a plasmid encoding sTGFβRII conjugated to the fragment crystallizable (Fc) portion of human immunoglobulin. The PEI-DNA polyplex formation was confirmed through gel retardation assay. Human corneal fibroblasts (HCFs) were …

Development Of A Bi-Directional Electronics Platform For Advanced Neural Applications, Luca Abbati

USF Tampa Graduate Theses and Dissertations

This work presents a high-voltage, high-precision bi-directional multi-channel system capable of stimulating neural activity through bi-phasic pulses of amplitude up to ∓50 V while recording very low-voltage responses as low as tens of microvolts. Most of the systems reported from the scientific community possess at least one of the following common limitations: low stimulation voltages, low gain capabilities, or insufficient bandwidth to acquire a wide range of different neural activities.

While systems can be found that present remarkable capabilities in one or more specific areas, a versatile system that performs over all these aspects is missing. Moreover, as many novel …

Structural Investigations Of Retinoid X Receptor Transcriptional Activation By Anti-Cancer Rexinoids, Leeann J. Boerma

All ETDs from UAB

Nuclear receptor (NR) protein retinoid X receptor (RXR) is a ligand-inducible transcription factor that binds retinoids for regulation of target genes. Agonist binding induces a major structural rearrangement in the ligand binding domain (LBD) and formation of the coactivator binding interface. RXR-signaling pathways control proliferation, differentiation, and growth in epithelial tissues. To understand how RXR agonists enhance signaling at the molecular level requires an understanding of how agonists induce structural and dynamical changes in the LBD to recruit coactivators for activation of anti-cancer relevant transcription. While most studies of NR activation center on the position of Helix 12 (H12)/activation function-2 …

Myosin Ii Regulates Actin Dynamics Critical For Structural Plasticity And Fear Memory Formation, Cristin Gavin

All ETDs from UAB

Dynamic changes to the actin cytoskeleton are required for synaptic plasticity and long-term memory formation. However, the molecular mechanisms that mediate filamentous actin (F-actin) dynamics during both activity-dependent synaptic potentiation and long-term memory encoding are poorly understood. Myosin II motor proteins are highly expressed in actin-rich growth structures in neurons, including dendritic spines. Recent work demonstrates that these molecular machines mobilize F-actin in response to synaptic stimulation and are required for memory encoding in CA1 hippocampus of rodents. The aims of this project were two-fold. First, we sought to establish if myosin II regulates actin filament polymerization necessary for structural …

Circuit Development In The Dorsal Lateral Geniculate Nucleus (Dlgn) Of The Mouse., Tania Seabrook

Theses and Dissertations

The visual system is one of the most widely used and best understood sensory systems and the dorsal lateral geniculate nucleus (dLGN) of the mouse has emerged as a model for investigating the cellular and molecular mechanisms underlying the development and activity-dependent refinement of sensory connections. Thalamic organization is highly conserved throughout species and the dLGN of the mouse possesses many features common to higher mammals, such as carnivores and primates. Two general classes of neuron are present within the dLGN, thalamocortical relay cells and interneurons, both of which receive direct retinal input. Axons of relay cells exit dLGN and …