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Problem Of Antibiotic Resistance In Patients With Acute Bacterial Cystitis And Treatment Options, Ahmet Karakaş, Vedat Turhan

Turkish Journal of Medical Sciences

No abstract provided.

Higher Il-6 And Il6:Igf Ratio In Patients With Barth Syndrome, Lori D. Wilson, Sadeeka Al-Majid, Cyril Rakovski, Christina D. Schwindt

Mathematics, Physics, and Computer Science Faculty Articles and Research

Background: Barth Syndrome (BTHS) is a serious X-linked genetic disorder associated with mutations in the tafazzin gene (TAZ, also called G4.5). The multi-system disorder is primarily characterized by the following pathologies: cardiac and skeletal myopathies, neutropenia, growth delay, and exercise intolerance. Although growth anomalies have been widely reported in BTHS, there is a paucity of research on the role of inflammation and the potential link to alterations in growth factors levels in BTHS patients.

Methods: Plasma from 36 subjects, 22 patients with Barth Syndrome (0.5 - 24 yrs) and 14 healthy control males (8 - 21 yrs) was …

Regulation Of Hepatic Gene Expression During Liver Development And Disease, Hui Ren

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

My first project was to investigate the role of Hepatocyte Nuclear Factor 1 (HNF1) and Nuclear Factor I (NFI) on alpha-fetoprotein (AFP) promoter activity during liver development. AFP is highly expressed in the fetal liver, silenced at birth, and remains at very low levels in the adult liver. A GA substitution located at -119 of the human AFP promoter is associated with hereditary persistence of AFP (HPAFP) expression in the adult liver (Hum Molec Genet, 1993, 2:379). The -120 region harbors overlapping binding sites for HNF1 and NFI. While it has been shown that the GA substitution increases HNF1 binding, …

A Diet Enriched In Stearic Acid Protects Against The Progression Of Type 2 Diabetes In Leptin Receptor Deficient Mice (Db/Db), Valerie Lynn Reeves

Theses and Dissertations--Physiology

Dietary saturated fat intake contributes to diabetes and cardiovascular disease, as shown in numerous animal and human studies. However, the hypothesis that stearic acid, a saturated fat, has beneficial effects on these conditions has not been adequately tested. Leptin receptor deficient mice (db/db) and wild-type mice were fed either chow or a high fat diet enriched in either stearic acid or oleic acid for ten weeks. The progression of diabetes was evaluated with blood glucose, insulin, and metabolic parameter measurements. At the conclusion of the study, pancreatic islet organization was examined, and blood, liver and feces were assayed for fatty …

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 …

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: …

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.

Artemis And Metnase Mediated Processing Of 3΄-Blocked Dna Lesions: Role In Radio/Chemoresistance And Dna Repair, Susovan Mohapatra

Theses and Dissertations

DNA double-strand breaks (DSB) with chemically modified end-termini are the most significant lesions resulting from radio/chemotherapeutic intervention of cancer and non homologous end-joining (NHEJ) factor Artemis nuclease has been implicated in the repair of such breaks. To examine whether the resolution of terminally blocked DNA DSBs is the biologically relevant function of Artemis, Artemis deficient fibroblasts were stably complemented with wild type or an endonuclease deficient D165N mutant Artemis. Physiological levels of wild type (WT) Artemis completely restored DSB repair proficiency and resistance to γ-radiation, bleomycin, and neocarzinostatin. Cells expressing the D165N mutants remained as chemo/radiosensitive and as repair deficient …

The Dermatan Sulfate Proteoglycan Decorin Modulates Α2Β1 Integrin And The Vimentin Intermediate Filament System During Collagen Synthesis., Oliver Jungmann, Katerina Nikolovska, Christian Stock, Jan-Niklas Schulz, Beate Eckes, Christoph Riethmüller, Rick T Owens, Renato V Iozzo, Daniela G Seidler

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Decorin, a small leucine-rich proteoglycan harboring a dermatan sulfate chain at its N-terminus, is involved in regulating matrix organization and cell signaling. Loss of the dermatan sulfate of decorin leads to an Ehlers-Danlos syndrome characterized by delayed wound healing. Decorin-null (Dcn(-/-)) mice display a phenotype similar to that of EDS patients. The fibrillar collagen phenotype of Dcn(-/-) mice could be rescued in vitro by decorin but not with decorin lacking the glycosaminoglycan chain. We utilized a 3D cell culture model to investigate the impact of the altered extracellular matrix on Dcn(-/-) fibroblasts. Using 2D gel electrophoresis followed by mass spectrometry, …

Infectious Intracranial Aneurysms: Collaboration For Treatment Success, Erin M. Conahan Rn, Bsn, Cnrn

Patient Care Services / Nursing

No abstract provided.

Proteasome Regulation Of Caspase-8: Significance In Cancer, Michael Vincent Fiandalo

Theses and Dissertations--Molecular and Cellular Biochemistry

Anti-tumor therapeutic strategies based on combinations of chemotherapeutic agents with a death inducing ligand such as TNF-α Related Apoptosis Inducing Ligand (TRAIL), are directed towards selective and effective cancer cell apoptosis and enhanced therapeutic response. We previously demonstrated that proteasome inhibition sensitizes TRAIL resistant prostate cancer cells to TRAIL-mediated apoptosis via stabilization of the active p18 subunit of initiator caspase-8. The present study investigated the functional link between caspase-8 and the proteasome, by analyzing the impact of caspase-8 ubiquitination and proteasomal degradation on the outcomes of the extrinsic apoptosis pathway in cancer cells. Caspase-8 ubiquitination status was assessed by polyubiquitin …

Cns Neural/Glial Progenitors As Targets Of Hiv-1 And Opiates: Effects On Proliferation And Population Dynamics May Alter Behavior Outcomes., Yun Kyung Hahn

Theses and Dissertations

Human immunodeficiency virus (HIV) infected patients with a history of injection opiate abuse have higher incidences of acquired immunodeficiency syndrome (AIDS) and neurological dysfunction. The use of combined anti-retroviral therapy has significantly reduced the prevalence of mortality and progression to AIDS. Due to extended life expectancy, these patients are still at a great risk for HIV-associated neurological disorders and impairment in their later life. Neural progenitor cells (NPCs) play critical roles in brain growth and repair after injury and insult. Pediatric HIV patients whose glial populations are still developing are especially at risk for central nervous system (CNS) damage. Our …

Hiv Rna Suppression And Immune Restoration: Can We Do Better?, Marilia Rita Pinzone, Michelino Di Rosa, Bruno Cacopardo, Giuseppe Nunnari

Department of Microbiology and Immunology Faculty Papers

HAART has significantly changed the natural history of HIV infection: patients receiving antiretrovirals are usually able to control viremia, even though not all virological responders adequately recover their CD4+ count. The reasons for poor immune restoration are only partially known and they include genetic, demographic and immunologic factors. A crucial element affecting immune recovery is immune activation, related to residual viremia; indeed, a suboptimal virological control (i.e., low levels of plasma HIV RNA) has been related with higher levels of chronic inflammation and all-cause mortality. The sources of residual viremia are not yet completely known, even though the most important …

Posttranslational Modification Of Vesicular Stomatitis Virus Glycoprotein, But Not Jnk Inhibition, Is The Antiviral Mechanism Of Sp600125, Sabrina Marozin, Jennifer Altomonte, Sibylle Apfel, Phat X. Dinh, Enrico De Toni, Antonia Rizzani, Andreas Nüssler, Nobuyuki Kato, Roland M. Schmid, Asit K. Pattnaik, Oliver Eberta

School of Veterinary and Biomedical Sciences: Faculty Publications

Vesicular stomatitis virus (VSV), a negative-sense single-stranded-RNA rhabdovirus, is an extremely promising oncolytic agent for cancer treatment. Since oncolytic virotherapy is moving closer to clinical application, potentially synergistic combinations of oncolytic viruses and molecularly targeted antitumor agents are becoming a meaningful strategy for cancer treatment. Mitogenactivated protein kinase (MAPK) inhibitors have been shown to impair liver cell proliferation and tumor development, suggesting their potential use as therapeutic agents for hepatocellular carcinoma (HCC). In this work, we show that the impairment of MAPK in vitro did not interfere with the oncolytic properties of VSV in HCC cell lines. Moreover, the administration …

Identification Of Amino Acid Residues Important For Anti-Ifn Activity Of Porcine Reproductive And Respiratory Syndrome Virus Non-Structural Protein 1, Lalit Beura, Sakthivel Subramaniam, Hiep Vu, Byungjoon Kwon, Asit K. Pattnaik, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

The non-structural protein 1 (nsp1) of porcine reproductive and respiratory syndrome virus is partly responsible for inhibition of type I interferon (IFN) response by the infected host. By performing alanine-scanning mutagenesis, we have identified amino acid residues in nsp1α and nsp1β~ (the proteolytic products of nsp1) that when substituted with alanine(s) exhibited significant relief of IFNsuppression. A mutant virus (16-SA, in which residues 16-20 of nsp1β were substituted with alanines) encoding mutant nsp1β recovered from infectious cDNA clone was shown to be attenuated for growth in vitro and induced significantly higher amount of type I IFN transcripts in infected macrophages. …

Fusion Of A Fluorescent Protein To The Pul25 Minor Capsid Protein Of Pseudorabies Virus Allows Live-Cell Capsid Imaging With Negligible Impact On Infection, Kevin P. Bohannon, Patricia J. Sollars, Gary E. Pickard, Gregory A. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

In order to resolve the location and activity of submicroscopic viruses in living cells, viral proteins are often fused to fluorescent proteins (FPs) and visualized by microscopy. In this study, we describe the fusion of FPs to three proteins of pseudorabies virus (PRV) that allowed imaging of capsids in living cells. Included in this study are the first recombinant PRV strains expressing FP–pUL25 fusions based on a design applied to herpes simplex virus type 1 by Homa and colleagues. The properties of each reporter virus were compared in both in vitro and in vivo infection models. PRV strains expressing FP–pUL25 …

Staphylococcal Response To Oxidative Stress, Rosmarie Gaupp, Nagender Ledala, Greg A. Somerville

School of Veterinary and Biomedical Sciences: Faculty Publications

Staphylococci are a versatile genus of bacteria that are capable of causing acute and chronic infections in diverse host species. The success of staphylococci as pathogens is due in part to their ability to mitigate endogenous and exogenous oxidative and nitrosative stress. Endogenous oxidative stress is a consequence of life in an aerobic environment; whereas, exogenous osidative and nitrosative stress are often due to the bacteria's interaction with host immune systems. To overcome the deleterious effects of oxidative and nitrosative stress, staphylococci have evolved protection, detoxification, and repair mechanisms that are controlled by a network of regulators. In this review, …

Cross-Talk Between Nfkb And The Pi3-Kinase/Akt Pathway Can Be Targeted In Primary Effusion Lymphoma (Pel) Cell Lines For Efficient Apoptosis, Azhar Hussain, Saeeda O. Ahmed, Maqbool Ahmed, Omar S. Khan, Sally Al Abdul Mohsen, Leonidas C. Platanias, Khawla S. Al-Kuraya, Shahab Uddin

Centre for Regenerative Medicine & Stem Cell Research

Background: A number of constitutively activated signaling pathways play critical roles in the survival and growth of primary effusion lymphoma cells (PELs) including NFkB and PI3/AKT kinase cascades. NFkBis constitutively activated in a number of malignancies, including multiple myeloma, Burkitt’s lymphoma and diffuse large cell B-cell lymphoma. However, its role in primary effusion lymphoma has not been fully explored.
Methodology/Principal Findings: We used pharmacological inhibition and gene silencing to define the role of NFkB in growth and survival of PEL cells. Inhibition of NFkB activity by Bay11-7085 resulted in decreased expression of p65 in the nuclear compartment as detected by …

Increasing Parity Is Associated With Cumulative Effects On Memory, Laura M. Glynn

Psychology Faculty Articles and Research

BACKGROUND: The purpose of this investigation was to determine if reproductive experience is associated with cumulative effects on human memory performance during pregnancy and if these effects persist into the postpartum period.

METHODS: Verbal recall memory performance was assessed in 254 women four times during pregnancy and at 3 months postpartum. The relation between parity and memory function was evaluated with hierarchical linear modeling and analysis of covariance (ANCOVA).

RESULTS: The data indicate that the previously documented adverse effects of pregnancy on memory performance are compounded with successive pregnancies. During gestation and postpartum, multiparity was associated with poorer memory function, …

Finding A Cure For Venezuelan Equine Encephalitis Virus (Veev) Infection: The Search For The Antiviral Genes And Vaccine Development., Svetlana Atasheva

All ETDs from UAB

Venezuelan equine encephalitis virus (VEEV) is a re-emerging virus that causes a severe and often fatal disease in equids and humans. To date, despite a continuous public health threat, no vaccines or antiviral drugs against VEEV infection have been developed for human use. In this study we took advantage of accumulated knowledge of capsid protein function in viral replication, assembly and virus-host interactions. Besides being an integral part of the virion, capsid protein is the major determinant of VEEV pathogenesis. This protein is cytotoxic and induces cellular transcriptional shutoff as a countermeasure to the cellular antiviral response. We introduced targeted …

Modulation Of Capsule Production In Serotype 3 Streptococcus Pneumoniae, Melissa Ellis

All ETDs from UAB

Streptococcus pneumoniae is a Gram-positive pathogen and an important cause of community-acquired pneumonia and meningitis, and it can also cause otitis media and bacteremia. A major virulence factor of S. pneumoniae is its polysaccharide capsule which functions to prevent complement-mediated opsonophagocytosis. At least 93 distinct serotypes that vary in sugar composition and structure exist. S. pneumoniae can asymptomatically colonize the nasopharynx and transition to other body sites such as the lungs and blood causing invasive disease. The ability to regulate capsule production in these vastly different environments is critical for survival as low levels of capsule are necessary for colonization, …

Functional Collaboration Between Igf-1 Receptor And Growth Hormone Signaling Pathway, Yujun Gan

All ETDs from UAB

GH receptor (GHR) binds GH in its extracellular domain (ECD) to activate the GHR-associated cytoplasmic tyrosine kinase, JAK2. IGF-1 binds IGF-1R, a disulfide-linked heterotetramer with tyrosine kinase activity in its intracellular domain (ICD). Classically, IGF-1 is a GH effector in a “linear” GH→GHR→IGF-1→IGF-1R pathway. Our recent studies suggest IGF-1R also subserves GH signaling in several novel ways: 1) GH induces a GHR-JAK2-IGF-1R complex, whose formation is independent of tyrosine phosphorylation of any of the partners; 2) Cotreatment with IGF-1 augments acute GH signaling; 3) deletion of IGF-1R in primary osteoblasts or human prostate cancer cells blunts acute GH signaling. In …

Regulatory T Cells In The Fvb.Mdr1a-/- Model Of Colitis, Scott Tanner

All ETDs from UAB

Regulatory T cells (Treg) are necessary for the maintenance of immune homeostasis, and have been implicated in several autoimmune diseases, including inflammatory bowel disease (IBD). Most murine studies focusing on the function of Tregs have been done on the C57BL/6 or BALB/c background, creating a bias towards these two strains. In addition, it has been shown that C57BL/6 and BALB/c Tregs function in different manners. To further investigate potential strain differences in Treg phenotype and function, we chose to analyze FVB/N Tregs. Several differences were observed, including de-creased FVB/N Treg suppression in a non-cell contact dependent manner, decreased FVB/N and …

Siderophore-Mediated Iron Acquisition In Mycobacterium Tuberculosis, Ryan Wells

All ETDs from UAB

Mycobacterium tuberculosis is a dangerous human pathogen that has the capacity to adapt to and survive within the harsh phagosomal environment of macrophages. One obstacle that must be overcome by pathogens is to acquire iron, an essential component and cofactor of proteins required for vital cellular processes. M. tuberculosis meets its iron demands in the face of an array of sequestration strategies of the host by synthesizing and secreting two siderophores called mycobactin and carboxymycobactin. Siderophores are low molecular weight high affinity iron binding compounds that steal iron away from host stores and have been shown to be important for …

Retinoids And Abnormal Alveolar Development, Masheika L. James

All ETDs from UAB

Extremely preterm infants are at high risk for a form of chronic lung disease called bronchopulmonary dysplasia (BPD), which is characterized by impaired alveolar development. Exposure to hyperoxia and deficiency of vitamin A (VA) contribute to the development of BPD in preterm infants. Randomized controlled trials indicate VA supplementation decreases BPD and/or death. However, 25% of preterm infants continue to remain VA deficient despite supplementation, probably due to impairment in VA transport, VA is stored in the liver as retinyl esters which are transported to the lung and irreversibly metabolized into all-trans-retinoic acid (ATRA), the active metabolite. A combination of …

Mycobacterial Iron Acquisition Systems, Christopher M. Jones

All ETDs from UAB

Iron is an essential nutrient for the vast majority of organisms; yet, the availability of iron is limited to microorganisms due to the insolubility of ferric hydroxides and to pathogens by iron withholding strategies of their hosts. Many bacteria produce small, high-affinity iron chelators called siderophores to scavenge iron from the environment. In addition, many bacterial pathogens have evolved mechanisms to steal host iron contained in heme, hemoglobin, or transferrin. Mycobacteria are unique genera of bacteria represented by the notorious pathogens Mycobacterium tuberculosis and Mycobacterium leprae, the causative agents of tuberculosis (TB) and leprosy, respectively. Tuberculosis remains a global health …

Transcriptional Regulation Of Gfap, Sujeong Yeo

All ETDs from UAB

Glial fibrillary acidic protein (GFAP) is an astrocytic intermediate filament protein whose levels are increased in response to CNS injuries. Aim one of my thesis is to find the regulatory elements of the GFAP promoter responsible for its expression properties using a transgenic approach, since previous studies showed inconsistent results between in vitro and in vivo approaches. Two contiguous DNA segments previously implicated in transcriptional control of the GFAP gene, the B region (bp -1612 to -1489), and the C1.1 and C1.2 regions (bp -1488 to -1399), were analyzed. Block mutation of each of 4 contiguous sequences together spanning the …

Analysis Of Ergothioneine Production In Mycobacterium Tuberculosis, Loni Ann Guidry

All ETDs from UAB

Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, currently infects more than two billion people worldwide. Mtb is a highly adaptable pathogen, capable of modifying its metabolism in response to its environment. We previously showed that Mtb WhiB3 is a redox-responsive regulator of core intermediary metabolism and lipid anabolism through which it maintains redox homeostasis. In this work, through the use of metabolomic analysis and a novel radioactive thin layer chromatography assay, we discovered that WhiB3 regulates the production of the intracellular thiol ergothioneine (ergo) when using immunomodulatory lipid precursors as the major carbon source. Our results suggest that this …

Mitochondrial Lysyl-Trna Synthetase Independent Import Of Trna Lysine Into Yeast Mitochondria., Naresh Babu V Sepuri, Madhavi Gorla, Michael P King

Department of Biochemistry and Molecular Biology Faculty Papers

Aminoacyl tRNA synthetases play a central role in protein synthesis by charging tRNAs with amino acids. Yeast mitochondrial lysyl tRNA synthetase (Msk1), in addition to the aminoacylation of mitochondrial tRNA, also functions as a chaperone to facilitate the import of cytosolic lysyl tRNA. In this report, we show that human mitochondrial Kars (lysyl tRNA synthetase) can complement the growth defect associated with the loss of yeast Msk1 and can additionally facilitate the in vitro import of tRNA into mitochondria. Surprisingly, the import of lysyl tRNA can occur independent of Msk1 in vivo. This suggests that an alternative mechanism is present …

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 …