Digital Commons Network^™

Neural Network Model For Instruments That Store And Retrieve Sequential Information, Philip W. Landfield, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Patents

A method and design is provided for distributing and storing sets of temporally ordered information in a systematic and sequential fashion. This method is based on a model of how the brain functions in the distribution and storage of temporally ordered memories, but it can also be applied to the design of new biological, electronic or optical devices. These devices may be used in the testing and development of new therapeutic drugs, in the detection of toxic agents or impaired performance, or in the development of new industrial and consumer devices in which the orderly storage of sequential information is …

Metabolic Oscillations In Pancreatic Islets Depend On The Intracellular Ca2+ Level But Not Ca2+ Oscillations, Matthew J. Merrins, Bernard Fendler, Min Zhang, Arthur Sherman, Richard Bertram, Leslie S. Satin

Pharmacology and Toxicology Publications

Abstract

Plasma insulin is pulsatile and reflects oscillatory insulin secretion from pancreatic islets. Although both islet Ca²⁺ and metabolism oscillate, there is disagreement over their interrelationship, and whether they can be dissociated. In some models of islet oscillations, Ca²⁺ must oscillate for metabolic oscillations to occur, whereas in others metabolic oscillations can occur without Ca²⁺ oscillations. We used NAD(P)H fluorescence to assay oscillatory metabolism in mouse islets stimulated by 11.1 mM glucose. After abolishing Ca²⁺ oscillations with 200 μM diazoxide, we observed that oscillations in NAD(P)H persisted in 34% of islets (n = 101). …

Treatment Strategies In Acute Myelogenous Leukemia : Investigating Hsp90 And P53 As Targets, Jennifer M. Napper

Theses, Dissertations and Capstones

Acute myelogenous leukemia (AML) is the deadliest of the lymphatic and bone marrow cancers. Patients diagnosed with AML have a five year survival rate of 23.4%. AML is characterized by an accumulation of undifferentiated and functionless myeloid precursors in the bone marrow and blood. Heat shock protein 90 (Hsp90) inhibitors, such as 17-AAG, an analog of geldanamycin (GM), are currently undergoing phase I, and II and III clinical trials for various cancers with mixed results. I found distinct responses to 17-AAG treatment among the AML cell lines tested. I also discovered two mutant TP53 alleles in Kasumi-3 cells, an AML …

Role Of Genetics In Prediction Of Coronary Artery Disease, Andrey Yuabov

The Science Journal of the Lander College of Arts and Sciences

The following is the introduction of this article: Coronary arteries disease (CAD) is a leading cause of death in United States and rest of the world. It mostly involves atherogenic formation within the walls of the coronary arteries, which in turn restricts the adequate perfusion to the heart muscle. This leads to myocardial infarction and sudden death. In the past few decades the theories of coronary arteries disease pathogenesis have changed. The facts reveal that the onset of the disease can develop as early as childhood. The degree of the disease gradually progresses in stages and it is regarded as …

Regulation Of Neuronal Excitability: New Mechanisms For Slow Afterhyperpolarization Activation And Modulation, Claudio Alberto Villalobos

Wayne State University Dissertations

One of the most characteristic features of pyramidal cells in the prefrontal cortex (PFC) is that they present a slow afterhyperpolarizing current (I_sAHP) that plays a critical role in the regulation of neuronal excitability. This current is modulated by receptors acting via GΑ_q/11 G proteins, thus it is thought that neurotransmitters regulate neuronal excitability through the inhibition of this current. I_sAHP is known to be mediated by calcium-activated potassium channels, however, neither the identity of the channel underlying this current nor its mechanism of activation are yet well understood. Recent reports have questioned a direct role …

Raman Spectroscopic Modeling Of T- Lymphocyte Activation And Detection Of Acute Renal Allograft Rejection, Kristian L. Brown

Wayne State University Dissertations

ABSTRACT

RAMAN SPECTROSCOPIC MODELING OF T-LYMPHOCYTE ACTIVATION AND DETECTION OF ACUTE RENAL ALLOGRAFT REJECTION

By

KRISTIAN L. BROWN

2010

Advisor: Gregory Auner, PhD

Major: Biomedical Engineering

Degree: Doctor of Philosophy

Despite the advances made in the area of kidney transplantation, the disparity between the demand and available donated organs remains a dominant and unresolved issue. Given the paucity of available renal allografts the preservation of existing grafts is vital. One factor that has negatively impacted renal allograft survival is acute rejection (AR). Traditionally, kidney transplant centers have used elevations in serum creatinine as a screening tool for detecting AR. However, …

In-Frame Mutagenesis Of Genes Encoding A Selenium-Dependent Molybdenum Hydroxylase And Putative Accessory Proteins In Enterococcus Faecalis, Christopher J. Mallard

Electronic Theses and Dissertations

Enterococcus faecalis is a well known nosocomial drug resistant pathogen that is responsible for urinary tract infections, bacteremia, wound infections and endocarditis through the formation of biofilms. It has been shown that 68 genes present within the core genome of E. faecalis are upregulated in biofilm formation. One of those 68 genes is a putative seleniumdependent molybdenum hydroxylase (SDMH). Adjacent to this gene are a series of open reading frames that have been postulated to play a role in the maturation of a labile selenium cofactor. The biosynthesis of this labile cofactor has yet to be studied at either the …

Chronic Inflammatory Responses To Microgel-Based Implant Coatings, Amanda W. Bridges, Rachel E. Whitmire, Neetu Singh, Kellie L. Templeman, Julia E. Babensee, L. Andrew Lyon, Andrés J. García

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Inflammatory responses to implanted biomedical devices elicit a foreign body fibrotic reaction that limits device integration and performance in various biomedical applications. We examined chronic inflammatory responses to microgel conformal coatings consisting of thin films of poly(N-isopropylacrylamide) hydrogel microparticles cross-linked with poly(ethylene glycol) diacrylate deposited on poly(ethylene terephthalate) (PET). Unmodified and microgel-coated PET disks were implanted subcutaneously in rats for 4 weeks and explants were analyzed by histology and immunohistochemistry. Microgel coatings reduced chronic inflammation and resulted in a more mature/organized fibrous capsule. Microgel-coated samples exhibited 22% thinner fibrous capsules that contained 40% fewer cells compared to unmodified PET disks. …

Differential Impact Of Tumor Suppressor Pathways On Dna Damage Response And Therapy-Induced Transformation In A Mouse Primary Cell Model., A Kathleen Mcclendon, Jeffry L Dean, Adam Ertel, Erik S Knudsen

Department of Cancer Biology Faculty Papers

The RB and p53 tumor suppressors are mediators of DNA damage response, and compound inactivation of RB and p53 is a common occurrence in human cancers. Surprisingly, their cooperation in DNA damage signaling in relation to tumorigenesis and therapeutic response remains enigmatic. In the context of individuals with heritable retinoblastoma, there is a predilection for secondary tumor development, which has been associated with the use of radiation-therapy to treat the primary tumor. Furthermore, while germline mutations of the p53 gene are critical drivers for cancer predisposition syndromes, it is postulated that extrinsic stresses play a major role in promoting varying …

Reduced Hamster Usage And Stress In Propagating Leishmania Chagasi Promastigotes Using Cryopreservation And Saphenous Vein Inoculation, Soi Meng Lei, Amanda E. Ramer-Tait, Rebecca R. Dahlin-Laborde, Kathleen Mullin, Jeffrey K. Beetham

Amanda Ramer-Tait Publications

Leishmania chagasi, a causal agent of visceral leishmaniasis, requires passage through lab animals such as hamsters to maintain its virulence. Hamster infection is typically accomplished via cardiac puncture or intraperitoneal injection, procedures accompanied by risks of increased animal stress and death. The use of the hamster model also necessitates a regular supply of infected animals, because L. chagasi parasites newly isolated from an infected hamster can be grown in culture for only several weeks before loss of function/phenotype occurs. In an effort to decrease animal usage and animal stress, experiments were performed to assess a more gentle inoculation …

Mir-107 Is Reduced In Alzheimer's Disease Brain Neocortex: Validation Study, Peter T. Nelson, Wang-Xia Wang

Pathology and Laboratory Medicine Faculty Publications

MiR-107 is a microRNA (miRNA) that we reported previously to have decreased expression in the temporal cortical gray matter early in the progression of Alzheimer's disease (AD). Here we study a new group of well-characterized human temporal cortex samples (N=19). MiR-107 expression was assessed, normalized to miR-124 and let-7a. Correlation was observed between decreased miR-107 expression and increased neuritic plaque counts (P< 0.05) and neurofibrillary tangle counts (P< 0.02) in adjacent brain tissue. Adjusted miR-107 and BACE1 mRNA levels tended to correlate negatively (trend with regression P< 0.07). In sum, miR-107 expression tends to be lower relative to other miRNAs as AD progresses.

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

Pharmacy Faculty Articles and Research

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

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

Can Dynamic Multidetector Computerized Tomography Detect Renal Cell Carcinoma Subtypes?, Ayhan Di̇ri̇m, Ni̇hal Tutar, Levent Peşki̇rci̇oğlu, Hüseyi̇n Çeli̇k, Mehmet İlteri̇ş Teki̇n, Hakan Özkardeş

Turkish Journal of Medical Sciences

To evaluate the efficacy of the biphasic and triphasic dynamic multidedector computerized tomography (MDCT) in the preoperative prediction of histological subtypes of renal cell carcinoma (RCC). Materials and methods: The preoperative dynamic MDCT findings of 51 patients with renal mass who had undergone nephrectomy were reviewed retrospectively. Twenty-five of the patients had biphasic (portal and excretory) and 26 had triphasic (arterial, portal, and excretory) MDCT images. Tumor size, presence of calcification, tumor-aorta attenuation values in all phases and homogeneicity of the tumor were noted for every patient. In heterogeneous tumors, the minimum and maximum attenuation values were noted to determine …

Loss Of The Sin3 Transcriptional Corepressor Results In Aberrant Mitochondrial Function, Valerie L. Barnes, Bethany S. Strunk, Icksoo Lee, Maik Hüttemann, Lori A. Pile

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

SIN3 is a transcriptional repressor protein known to regulate many genes, including a number of those that encode mitochondrial components.

Results

By monitoring RNA levels, we find that loss of SIN3 inDrosophilacultured cells results in up-regulation of not only nuclear encoded mitochondrial genes, but also those encoded by the mitochondrial genome. The up-regulation of gene expression is accompanied by a perturbation in ATP levels in SIN3-deficient cells, suggesting that the changes in mitochondrial gene expression result in altered mitochondrial activity. In support of the hypothesis that SIN3 is necessary for normal mitochondrial function, yeastsin3null mutants exhibit very poor …

Asymptomatic Carriage Of Bacteria In Food Workers In Nilüfer District, Bursa, Turkey*, Kayihan Pala, Cüneyt Özakin, Nalan Akiş, Melda Sinirtaş, Suna Gedi̇koğlu, Hamdi̇ Ayteki̇n

Turkish Journal of Medical Sciences

This study was carried out in order to determine the nasal carriage of Staphylococcus aureus and the faecal carriage of Salmonella spp., Shigella spp., Yersinia enterocolitica, Listeria monocytogenes, and Escherichia coli O157:H7 in food industry workers. Materials and methods: During the study, face to face interviews were conducted with the workers and 9-item questionnaires regarding demographic information, working time, and periodical medical examinations were administered. In the study nasal swab specimens of 1115 individuals and faecal specimens of 1061 individuals were bacteriologically investigated. Results: The nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) was found to be significantly more common in …

A Novel Hand-Held Device For The Measurement Of Ocular Alignment, Uğur E. Altiparmak, Esra Karabulut, Eric R. Eggenberger

Turkish Journal of Medical Sciences

The measurement of ocular alignment can be challenging and difficult to reproduce. A method for the measurement of ocular alignment with accuracy, speed, and reproducibility would be a useful clinical addition. Materials and methods: A hand-held device consisting of a rotary prism and a red Maddox rod was constructed. This was used to evaluate 18 patients with ocular misalignment and the results were compared with the ones obtained using the prism cover testing. Results: The results from the hand-held device showed a close correlation with those of the prism cover test. Conclusion: The hand-held instrument is a useful method to …

Underestimated Role Of Alcohol At Skin Disinfection: Lipid Dissolving Property When Used In Association With Conventional Antiseptic Agents, Alp Yentür, İsmet Topçu, Ruşen Işik, Kenan Değerli̇, Süheyla Sürücüoğlu

Turkish Journal of Medical Sciences

After conventional aqueous disinfectant solutions, it was shown that microorganisms were still protected in hair follicles. We hypothesized that those aqueous disinfectant solutions when used in combination with alcohol may be more effective on the inhibition of recolonization of skin and therefore catheter tip colonization. Materials and methods: Skin surface samples were taken from epidural catheter insertion sites prior to catheterization, and before and after disinfection with different combinations of povidone-iodine, chlorhexidine, and alcohol. Before catheter removal, cultures were taken once more and tips of the catheters were cultured. Results: Catheter tip colonization and skin culture results of 10% povidone-iodine …

Absence Of Vancomycin-Resistant Enterococci (Vre) Despite The Presence Of Risk Factors: A Survey Of Rectal Carriage Of Vre*, Zeli̇ha Koçak Tufan, Selcan Arslan, Sali̇h Cesur, Cemal Bulut, Hasan Irmak, Sami̇ Kinikli, Ferah Ergi̇n, Ali̇ Kutta Çeli̇k, Ali̇ Pekcan Demi̇röz

Turkish Journal of Medical Sciences

The resistant organisms from patients and healthcare workers (HCWs) first colonized the gastrointestinal tract before causing infections in patients. In this study, presence of risk factors for vancomycin-resistant enterococci (VRE) colonization and the prevalence of rectal carriage of VRE among HCWs and hospitalized patients in the absence of an outbreak were investigated. Design: Cross-sectional study. Setting: A 600-bed training and research hospital. Materials and methods: A total of 508 intensive-care unit (ICU) patients and HCWs in these units were included. Risk factors such as previous antibiotic use, especially vancomycin and cephalosporin, the presence of invasive devices like catheters, and co-morbid …

Two Siblings With Netherton Syndrome, Selma Emre, Ahmet Meti̇n, D. Deni̇z Demi̇rseren, Ahu Yorulmaz, Aykut Onursever, Burçi̇n Kaftan

Turkish Journal of Medical Sciences

Netherton syndrome (NS) is a rare genodermatosis characterized by autosomal recessive inheritance pattern, unknown etiology, ichthyosiform cutaneous changes, atopic diathesis, and alterations in the hair shaft. As a result of aging coupled with immune deficiency, clinical symptoms may vary. Herein, we present 2 siblings with the characteristic cutaneous symptoms of NS, albeit with some differences between the siblings. Materials and methods: Two sisters presented to our clinic with sparse and brittle hair along with pruritic, erythematous, and scaling cutaneous lesions. Both patients underwent a clinical examination and laboratory analyses. Results: Based on the clinical and laboratory findings, both patients were …

The Association Of Tafi (Thrombin-Activatable Fibrinolysis Inhibitor) With Insulin Resistance And Components Of Metabolic Syndrome In Patients With Metabolic Syndrome, Alev Kural, Ahmet Omma, Hati̇ce Seval, Maci̇t Koldaş, Namik Yi̇ği̇t, Tülay Omma

Turkish Journal of Medical Sciences

To investigate the association of TAFI with components of metabolic syndrome and insulin resistance in patients with metabolic syndrome. Materials and methods: Patients between 20 and 70 years of age, who met at least 3 of the metabolic syndrome criteria, and had no known coronary artery disease were included in the study. The control group consisted of 20 healthy subjects with demographic characteristics similar to the patients. Fasting blood glucose, HbA1c, lipid profile, insulin, microalbumin, and TAFI Ag levels were investigated in the patients and controls. Insulin resistance was calculated according to the HOMA-IR [(fasting plasma insulin (\muIU/ml) x fasting …

Effects Of Aqueous Garlic Extract On Oxidant/Antioxidant Status In 32d And 32dp210 Cell Lines, Aslihan Avci, Asuman Sunguroğlu, İmge B. Ergüder, Güvem Gümüş Akay, Erdi̇nç Devri̇m, Pinar Özkal Baydin, Nuray Varol, İlker Durak

Turkish Journal of Medical Sciences

To investigate the possible effects of aqueous garlic extract on the oxidant/antioxidant status and apoptosis in 32D (wild type mouse myeloid cell = normal) and 32Dp210 (BCR-ABL fusion gene (+) mouse myeloid cell = Chronic Myelocytic Leukemia cells) cell lines. Materials and methods: Aqueous garlic extract (10% w/v) was added into the cell line media with 2 different final concentrations (0.4% and 1%). At 0 h and at 24, 48, and 72 h later, the oxidant (malondialdehyde (MDA) level, and xanthine oxidase (XO) enzyme activity) and antioxidant (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) enzyme activities) parameters were …

Histomorphometric Study On The Effect Of Low Dose Deltamethrin On The Developing Cerebellar Cortex, Mohd Asnizam Asari, Mohammad Shukri Abdullah, Zul Izhar Mohd Ismail

Turkish Journal of Medical Sciences

Deltamethrin is a widely used type II pyrethroid-based insecticide. Studies have indicated that neonatal exposure to deltamethrin, even at relatively low doses, results in behavioral and neurological changes. In the present study, the effect of early neonatal exposure to low doses of deltamethrin on the histogenesis of the cerebellar cortex was investigated. Materials and methods: Sprague Dawley male pups were exposed to deltamethrin daily at a dose of 1 mg/kg via intraperitoneal injection from the 2nd to the 5th postnatal day and sacrificed on postnatal days 6, 14, and 21. Following intracardiac perfusion, the cerebellum was removed, embedded with paraffin …

The Prevalence Of Trichomonas Vaginalis Infection Among Patients That Presented To Hospitals In The Kermanshah District Of Iran In 2006 And 2007, Abdolali Chalechale, Isaac Karimi

Turkish Journal of Medical Sciences

To determine the prevalence of Trichomonas vaginalis (Tv) among women that presented to hospitals in the Kermanshah district of Iran in 2006 and 2007. Materials and methods: This retrospective study included 33.690 women that presented to primary pathology laboratories in Kermanshah. Vaginal and cervical swabs were collected, and then stained with Papanicolaou (Pap) stain. Additionally, seasonal variations in the prevalence rate were compared to identify significant differences in the prevalence of Tv according to season. Results: Among the 33,690 women, 300 were infected with Tv (a prevalence rate of 0.9%). The 30-39-year-old age group had a significantly higher prevalence of …

Prospects And Pits On The Path Of Biomimetics: The Case Of Tooth Enamel, Vuk Uskoković

Pharmacy Faculty Articles and Research

This review presents a discourse on challenges in understanding and imitating the process of amelogenesis in vitro on the molecular scale. In light of the analysis of imitation of the growth of dental enamel, it also impends on the prospects and potential drawbacks of the biomimetic approach in general. As the formation of enamel proceeds with the protein matrix guiding the crystal growth, while at the same time conducting its own degradation and removal, it is argued that three aspects of amelogenesis need to be induced in parallel: a) crystal growth; b) protein assembly; c) proteolytic degradation. A particular emphasis …

Subcellular Localization Of The Non-Structural Proteins 3c And 3cd Of The Honeybee Virus Deformed Wing Virus, Cierra Nichole Danko

Honors Theses

Apis mellifera L., the European honeybee, is a crucial pollinator of many important agricultural crops in the United States. Recently, honeybee colonies have been affected by Colony Collapse Disorder (CCD), a disorder in which the colony fails due to the disappearance of a key functional group of worker bees. Though no direct causalrelationship has been confirmed, hives that experience CCD have been shown to have a high incidence of Deformed Wing Virus (DWV), a common honeybee virus. While the genome sequence and gene-order of DWV has been analyzed fairly recently, few other studies have been performed to understand the molecular …

Developing A Screen To Identify Small Molecule Inhibitors That Disrupt Protein-Protein Interactions In Mycobacteria, Deborah Mai

All ETDs from UAB

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB) and infects nearly one-third of the world's population. The same TB chemotherapeutic regimen has been administered for more than 50 years, and can be improved by developing innovative methods to discover new anti-TB drugs. This work describes a newly established high-throughput screen (HTS) platform technology based on Mycobacterial-Protein Fragment Complementation (M-PFC) to identify small molecule inhibitors of protein-protein interactions in mycobacteria. M-PFC HTS employs both whole cell and target-based approaches, and offers flexibility in selecting an appropriate protein interaction target for HTS. Selectable drug targets can include interactions of essential …

Molecular Mechanisms Of Breast Cancer Metastasis: Gap Junction Intercellular Communication And The Bone Microenvironment, Thomas Morgan Bodenstine

All ETDs from UAB

Metastatic disease accounts for the overwhelming majority of cancer related deaths. More specifically, breast cancer remains one of the leading causes of death in women and breast cancer cells metastasize to bone more than any other secondary site. Upon arriving within the bone microenvironment, breast cancer cells interact with bone marrow cells, leading to changes in bone biology that favor growth of the cancer cells. Additionally, some cancer cells are capable of direct cellular communication with cells at metastatic sites via dysregulation of a family of proteins known as connexins. This direct, physical communication is known as gap junctional intercellular …

Preclinical Pharmacology Of Novel Synthetic Iminoquinones As Anticancer Agents, Scharri Ezell

All ETDs from UAB

Prostate cancer is the most common male malignancy and the second leading cause of cancer related death in the United States. Despite recent advances in the detection, diagnosis, and treatment of prostate cancer, there is a need for more effective therapies. Unfortunately, most conventional therapeutic modalities, such as androgen ablation therapy, frequently result in androgen-independent cancers. These cancers are typically more aggressive, metastatic, and resistant to chemotherapeutic agents than androgen-dependent prostate cancer. Therefore, agents that are effective against both androgen-sensitive and androgen-independent, as well as genetically diverse cancers are critically needed. The objective of the dissertation research was to address …

The Overexpression Of Homeotic Complex Gene Ultrabithorax In The Post-Embryonic Neuronal Lineages Of The Ventral Nervous System In Drosophila Melanogaster, Katie Dry

Master’s Theses

This study uses a molecular technique called MARCM (Mosaic Analysis with a Repressible Cell Marker) to label neuronal lineages that overexpress the Hox gene Ultrabithorax (Ubx) in an unlabeled, wild type background. The results indicate that the overexpression of Ubx is sufficient to transform more anterior neuronal lineages to themorphology of their more posterior counterparts. The data presented here begin to elucidate the role that the Hox genes have in shaping segment-specific neural connections in the post-embryonic ventral nervous system.

Immunomodulatory Effect Of Host And Fungal Eicosanoids During Host-Pathogen Interactions With Candida Albicans, Gitanjali Kundu

Wayne State University Dissertations

Candida albicans, an opportunistic fungal pathogen, poses a significant clinical threat to immunocompromised patients. Diseases associated with this fungus ranges from superficial mucosal infection to life-threatening systemic candidiasis. The mechanisms by which Candida persists at mucosal surfaces in the face of an adaptive response are unclear. Candida produces immunomodulatory oxylipins that cross-react functionally with host eicosanoids, which are considered to play important role in regulating innate and adaptive immune responses. Our objective was to characterize the role of prostaglandins produced by the host and this fungus during host pathogen interactions, both in vitro with dendritic cells (DCs) and macrophages, and …