Medical Sciences Commons^™

Cobalamin Deficiency During Pregnancy Expressed As Elevated Urine Methylmalonic Acid Levels Determined By A Photometric Assay, Osman Meti̇n İpçi̇oğlu, Mustafa Gültepe, Ömer Özcan

Turkish Journal of Medical Sciences

Aim: Deficiency of cobalamin and folate during pregnancy is associated with megaloblastic anemia. Lower levels of folate and vitamin B12 were reported in mothers whose offspring had neural tube defects compared to unaffected controls. Increased methylmalonic acid (MMA) levels are a sensitive indicator of mild vitamin B12 deficiency and elevated homocysteine levels denote vitamin B12 or folate deficiency. We aimed to evaluate cobalamin state in pregnancy by using urine MMA levels determined by an economic spectrophotometric method. Materials and Methods: For this cross-sectional study, plasma total homocysteine (tHcy), serum folate and vitamin B12, and urine MMA levels were measured in …

K26 Antigen From L. Infantum Mon1: Sequence Based Function-Localization Analysis, Behrooz Darbani, Mahmoud Toorchi, Safar Farajnia, Seyyed Abolghasem Mohammadi, C. Neal Stewart

Turkish Journal of Medical Sciences

No abstract provided.

Diagnostic Performance Of Qus For Identifying Osteoporosis In Postmenopausal Turkish Women, Ayfer Gemalmaz, Güzel Di̇şci̇gi̇l, Cengi̇z Ceylan

Turkish Journal of Medical Sciences

Aim: The aims of this study were to evaluate the ability of quantitative ultrasound (QUS) to identify osteoporosis in postmenopausal women on the basis of dual-energy X-ray absorptiometry (DXA) T-scores, the best predictor of osteoporotic fractures, and to find a cut-off value for QUS with the optimum sensitivity and specificity, in order to select postmenopausal women for DXA referral. Materials and Methods: This study included 116 postmenopausal women attending Adnan Menderes University Family Medicine Clinic in Aydin. Bone density was measured at the calcaneus using QUS and at lumbar spine and femoral neck with DXA. Receiver operating characteristic analysis was …

Autopsy Status And Pathologists’ Attitude Towards Autopsy In Turkey, Kemal Kösemehmetoğlu, Ali̇ Riza Tümer, Alp Usubütün

Turkish Journal of Medical Sciences

Aim: While there have been efforts to slow the recent declining trend in autopsy practice in the world, in Turkey there is already a low level of medical autopsy audit, practically nearing zero. In this study, we determine and evaluate the autopsy status in Turkey; reveal pathologists' attitudes towards autopsy practice; propose several factors to explain current autopsy audit; and discuss differences in Turkey's autopsy practice with that of the rest of the world. Materials and Methods: We directed a questionnaire to 85 pathologists and requested autopsy numbers from 50 universities for the period 1995 to 2003. Results: Mean values …

Faculty Publications 2006, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 638 publications.

Genetic Microheterogeneity And Phenotypic Variation Of Helicobacter Pylori Arginase In Clinical Isolates, Justin Hovey, Emily Watson, Melanie Langford, Ellen Hildebrandt, Sangeetha Bathala, Jeffrey Bolland, Domenico Spadafora, George Mendz, David Mcgee

School of Biological Sciences: Faculty Publications

Background: Clinical isolates of the gastric pathogen Helicobacter pylori display a high level of genetic macro- and microheterogeneity, featuring a panmictic, rather than clonal structure. The ability of H. pylori to survive the stomach acid is due, in part, to the arginase-urease enzyme system. Arginase (RocF) hydrolyzes L-arginine to L-ornithine and urea, and urease hydrolyzes urea to carbon dioxide and ammonium, which can neutralize acid.

Results: The degree of variation in arginase was explored at the DNA sequence, enzyme activity and protein expression levels. To this end, arginase activity was measured from 73 minimally-passaged clinical isolates and six laboratory-adapted strains …

Identification Of A 17-Nucleotide Splicing Enhancer In Hpv-16 L1 That Counteracts The Effect Of Multiple Hnrnp A1-Binding Splicing Silencers, Ziaomin Zhao, Joanna Fay, Stefan Schwartz, Helen Lambkin

Articles

Human papillomavirus type 16 (HPV-16) infections can in rare cases persist and cause lesions that may progress to cervical cancer. Cells in the lesions are not permissive for virus production, nor are cervical cancer cells. The intracellular environment is such that it prevents production of the highly immunogenic, viral structural proteins L1 and L2. One may speculate that inhibition of L1 and L2 expression is a prerequisite for persistence and cancer progression.We have therefore investigated how expression of HPV-16 L1 is regulated.We found that the only splice site in the HPV-16 late region, which is used to produce L1 mRNAs, …

Mutagenesis Of The Catalytic Triad Of Tissue Transglutaminase Abrogates Coeliac Disease Serum Iga Autoantibody Binding, Greg Byrne, Fergus Ryan, John Jackson, Con Feighery, Jacinta Kelly

Articles

Background and aims: Tissue transglutaminase (tTG) is an autoantigen in coeliac disease and the related disorder, dermatitis herpetiformis. The detection of autoantibodies directed against tTG is a highly specific marker of coeliac disease; however, it is unclear if there is a role for these autoantibodies in the disease process. The aim of this study was to investigate whether the catalytic triad of tTG is targeted by coeliac disease autoantibodies. Methods: A full-length wild-type recombinant tTG and a novel site-directed mutagenic variant lacking the catalytic triad were produced in Escherichia coli. Serum samples from 61 biopsy-proven coeliac disease and 10 dermatitis …

Localization And Function Of G2e3, William Samuel Brooks

All ETDs from UAB

A microarray study was performed which identified G2E3 as a novel, putative ubiquitin ligase that was both G2/M-specific in expression and down regulated at the transcriptional level following DNA damage by γ-irradiation. The initial characterization of this protein is described herein. G2E3 is composed of three PHD/RING (plant homoedomain/really interesting new gene) domains within its amino-terminal half and a carboxy-terminal HECT (homologous to E6AP carboxy-terminus) domain. G2E3 is regulated in part by its subcellular localization. The protein normally resides within the nucleoplasm of cultured cells and distinctly within the nucleolus of HeLa cells. G2E3 is a nucleo-cytoplasmic shuttling protein with …

Loss Of Pias3 Expression In Glioblastoma Multiforme Tumors:Implications For Stat-3 Activation And Gene Expression, Emily Claire Brantley

All ETDs from UAB

Glioblastoma multiforme (GBM) is the most common form of cancer in the central nervous system in adults. Because of the infiltrative and aggressive nature of GBM, current treatments including surgical resection, radiation and chemotherapy provide little benefit to patients diagnosed with this tumor. Median survival, after treatment, is less than one year. Despite advances in the basic understanding of cancer biology, this poor prognosis has remained virtually unchanged for several decades. Given the continuing difficulty of clinical treatment of GBMs, a molecular appreciation of relevant signaling pathways has grown. Signal Transducers and Activators of Transcription (STATs) function to activate gene …

Characterization And Functional Analysis Of Usp14, Stephen Lewis Crimmins

All ETDs from UAB

The ubiquitin proteasome system (UPS) is essential for regulated protein degrada-tion, a requirement for numerous neuronal process, including vesicle cycling, neuro-transmitter release, spine morphology, and synaptic plasticity. Better understanding of UPS function in neurons will increase our knowledge of neurological diseases caused by alterations in ubiquitin signaling. I utilized the ataxia (axJ) mice as a tool to study the UPS in the nervous system. The axJ mice have lowered expression of ubiquitin-specific protease 14 (Usp14) in all tissues; this decreased expression results from an intracisternal-A particle insertion into Usp14. The axJ mice are phenotypically indistinguishable from wild type littermates at …

Characterization Of A Novel Acetyltransferase Found Only In Pathogenic Strains Of Mycobacterium Tuberculosis, David K. Crossman

All ETDs from UAB

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is still a major threat to the human population. Roughly one third of the world population is asymptomatically infected and two million people die each year of TB. Effective treatments are available as a multi-drug regimen, but there is an ever increasing problem with the rise of multi-drug resistant strains that newer drug targets and a better understanding of how M. tuberculosis affects the host need to be elucidated. The primary target of M. tuberculosis in the human host is the macrophage where M. tuberculosis secretes virulence factors that inhibit various signal …

Coupling Selection Of The Hiv- 1 Trna Primer Used For Reverse Transcription With Viral Translation And Encapsidation, Uros V. Djekic

All ETDs from UAB

HIV-1 belongs to the Retroviridae family. A hallmark of retroviral replication is the process of reverse transcription. Viral reverse transcriptase requires placement of a cellular tRNA primer onto the primer binding site (PBS) in order to initiate conversion of the viral RNA genome into a double stranded DNA copy. Mutation of the HIV-1 PBS forces the virus to utilize the non-cognate primer. Even though extensive studies have been done over the past 15 years, the mechanism of HIV-1 primer selection has yet to be completely elucidated. HIV-1 captures free tRNA during a yet undefined step in viral replication. However, our …

The Role Of The Cytoskeleon In Achr Clustering, G Clement Dobbins

All ETDs from UAB

The human brain contains billions of neurons which are designed to receive and integrate a range of electrical and biochemical signals. The ability to convey information between these cells depends on synapses. A precise apposition between the pre and post synapse must exist for efficient transmission to occur. The neuromuscular junction (NMJ) has become a model for studying synaptogenesis. Although much is known about the steps in NMJ formation, only recently have there been insights into the mechanism behind NMJ development. Much of this research has focused on how acetylcholine receptors (AChRs) at the postsynapse form clusters directly apposed to …

A Study Into The Protein/Protein Interactions Involved In Hiv-1 Capsid Assembly, Chanel Catherine Douglas

All ETDs from UAB

The aim of this work was to build an understanding of the protein/protein interactions involved in HIV-1 capsid assembly as it relates to the condensation of capsid within the virion. This was undertaken in an attempt to (i) understand how capsid subunits recognize and interact with each other, (ii) gain insight into the protein-protein interactions involved in the process, and (iii) determine if the protein-protein interactions involved in virus cap-sid assembly can be used as a target for viral inhibition. Within this dissertation you will find two approaches to this investigation. The first examines the role of electrostatics in the …

Visualizing The Function And Migration Of T Cells, Kari J. Dugger

All ETDs from UAB

Lymphocytes are highly mobile cells that can travel throughout the body in response to a multitude of stimuli. Identifying lymphocyte trafficking patterns in vivo is essential for a complete understanding of immune function. Cell-cell and cell-tissue interactions in immune development and in lymphocyte response to stimuli can be comprehended with these investigations. Although the location of cell populations in various tissues at any given point in time may be investigated by techniques such as flow cytometry and immunofluorescence, these methods are not easily used in the assessment of dynamic cell migration patterns in vivo. In the past years, technologies for …

Molecular Determinants Of Picrotoxin Inhibition, Brian E. Erkkila

All ETDs from UAB

PTX is a non-competitive antagonist of many LGICs, and its site of action is believed to be within the ion-conducting pore. This study will examine, through the use of mutagenesis, electrophysiology and homology modeling, the binding interaction between the LGIC receptors and the PTX molecule. The data provides evidence that an interaction between the PTX molecule and uncharged polar amino acids at the 6’ level of the M2 transmembrane domain are essential for PTX inhibition. While the work will focus on the γ-aminobutyric type A receptor, the pharmacological and structural relevance is attributable to the LGIC family as a whole.

The Role Of Chloride In The Volume Regulation Of Human Glioma Cells, Nola Jean Ernest

All ETDs from UAB

According to the Central Brain Tumor Registry of the United States, the most common primary brain tumors are gliomas, tumors composed of cells of glial origin, most commonly astrocytes and oligodendrocytes. The most aggressive of these tumors are characterized by hyperproliferation, marked cellular and nuclear atypia, extensive infiltration into surrounding normal brain tissue, and large areas of cell and tissue death. Previous data published by our lab and others suggest that these biological processes may involve regulated cell volume changes. Using cell volume regulation in the presence of an anisosmotic challenge as a model for cell swelling and shrinkage, cell …

Protease Dysregulation: Role In Neutrophilic Inflammation In Cystic Fibrosis, Amit Gaggar

All ETDs from UAB

Cystic fibrosis (CF) is a lethal disorder characterized by abnormal epithelial ion transport; this disorder is characterized by an ongoing airway remodeling and neutrophilic inflammation. Much of the airway remodeling is due to activation of a group of enzymes known as proteases; human neutrophil elastase (HNE) is a prominent protease found in the CF airway. While specific cytokines/chemokines are well-known for their role in the inflammation seen in CF, it is unknown how the protease-rich environment in CF lung disease influences airway inflammation. Recently, our group has characterized a novel collagen-derived fragment, proline-glycine-proline (PGP), which causes neutrophil influx through mechanisms …

Pneumococcal Choline-Binding Protein A: Its Role In Virulence And Its Utility As A Streptococcus Pneumoniae Vaccine Antigen, David Tawayne Glover

All ETDs from UAB

Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. S. pneumoniae is a leading cause of pneumonia, meningitis, septicemia, and otitis media. Although all age groups can be affected, children and the elderly are espccially susceptible to infection. Currently there is a conjugate vaccine available for use, but this vaccine only contains capsular polysaccahride antigens from the seven most prevelant S. pneumoniae serotypes. The use of the conjugate vaccine has led to serotype shift, with more disease being caused by non-vaccine serotype bacteria. The studies presented in this dissertation identify and characterize a novel S. penumoniae vaccine candidate …

Protein Interaction And Cell Surface Trafficking Differences Between Wild-Type And Δf508 Cystic Fibrosis Transmembrane Conductance Regulator, Rebecca F. Goldstein

All ETDs from UAB

Cystic fibrosis (CF) is caused by mutation of one protein, the cystic fibrosis transmembrane conductance regulator (CFTR), which normally functions as a chloride channel at the apical surface of epithelial cells. The most common CFTR mutation results in the deletion of a single amino acid (phenylalanine) at position 508, which causes the protein to fold improperly. The ΔF508 CFTR is a temperature-sensitive (TS) processing mutant: At the restrictive temperature, 37°C, ΔF508 CFTR misfolds in the endoplasmic reticulum (ER) and is degraded, but at the permissive temperature, 27°C, it is “rescued” from degradation (rΔF508). In particular, rΔF508 CFTR folds correctly enough …

Interference With Hiv-1 Primer Selection By Sirna Directed To The Hiv-1 Primer Binding Site, Wenlong Han

All ETDs from UAB

The replication of Human immunodeficiency virus type 1 (HIV-1) is characterized by the process of reverse transcription, which converts the viral RNA genome into a DNA intermediate prior to integration into the host cell chromosome. The initiation of reverse transcription needs a cellular tRNA primer, which binds to a region in the viral RNA genome, designated as the primer binding site (PBS). The 18-nucleotide PBS region of HIV-1, which is complementary to the 3′ terminal 18 nucleotides of tRNALys,3, is absolutely conserved among all HIV-1. The highly conserved PBS is a very good target for HIV-1 therapy. My dissertation research …

A Role For P63 In The Regulati On Of Cell Cycle Progression And Cell Death, Eric Scott Helton

All ETDs from UAB

p63 is a member of the p53 family of transcription factors that is a critical regulator of epithelial development. Studies have shown that p63 does not appear to function as a classical tumor suppressor like p53. Instead, the expression pattern of p63 in cancers suggests that p63 retains the potential to function as either a tumor suppressor or an onco-protein. Here, we provide evidence describing the transcriptional activity of the p63 isoforms and provide mechanisms whereby p63 function is regulated in a context dependent manner. Our data shows that both the ΔNp63 and TAp63 variants retain the potential to regulate …

Regulation Of The Human Heme Oxygenase-1 Gene, Thomas D. Hock

All ETDs from UAB

The heme oxygenase-1 (HO-1) gene encodes a microsomal enzyme that catalyzes the conversion of heme to carbon monoxide, Iron, and biliverdin. HO-1 transcription is induced upon a plethora of cellular stresses including heme, heavy metal exposure, hy-poxia, oxidative stress and many others. The goal of this work was to explore the molecu-lar regulation of HO-1 transcription. Four DNase 1 hypersensitive sites are detected within the HO-1 promoter extending from ~-40bp to ~-9.2kb relative to the transcription start site. Dimethylsulfate (DMS) in vivo footprinting is shown for two regulatory re-gions and reveals nine protected guanines in all. Mutational analyses indicates that …

Prostate Cancer Chemoprevention With Genistein And Resveratrol In Models Of Spontaneously Developing Prostate Cancer, Curt E. Harper

All ETDs from UAB

Prostate cancer is the second leading cause of cancer-related death among men in the United States. The goal of this research was to investigate the potential of three nutriceutical polyphenols, genistein, resveratrol, and epigallocatechin-3-gallate (EGCG), to suppress prostate cancer. Cancer chemoprevention and mechanism of action studies were carried out in transgenic models of prostate cancer. In TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, resveratrol suppressed poorly differentiated tumors by 86%, whereas EGCG suppressed precancerous lesions, but failed to prevent late-stage prostate cancer. Agents that were chemopreventive in the TRAMP model were subsequently evaluated alone, and in combination, in the …

Quantitation Of Antiretrovirals In Alternative Matrices, Chantelle Bennetto Hood

All ETDs from UAB

The human immunodeficiency virus (HIV) pandemic is a growing concern, affecting almost 40 million people worldwide. Treatment for HIV infection consists of highly active antiretroviral therapy (HAART) to block different steps in the viral lifecycle, ultimately reducing HIV RNA to undetectable levels in the plasma. However, HIV RNA can be detected in numerous reservoirs outside of the blood despite the use of HAART. Therefore, measurement of antiretroviral (ARV) drugs in other biological matrices is important to broaden our understanding of HIV transmission, the development of viral resistance with sub-optimal ARV exposure, and fetal and neonatal drug exposure. This work describes …

Characterization Of A Global Regulatory Pathway In Streptococcus Pneumoniae, Greer E. Kaufman

All ETDs from UAB

Streptococcus pneumoniae is a versatile organism that adapts to many different environments in the host. S. pneumoniae can asymptomatically colonize the nasopharynx of humans. However, dissemination of the bacterium from the nasopharynx to different locations in the body can lead to invasive diseases such as pneumonia, bacteremia, and meningitis. How S. pneumoniae modulates factors that are important for survival in these niches has not been well characterized. In the studies described here, we propose that S. pneumoniae may modulate gene expression in these niches by sensing the different glu-cose concentrations via carbon catabolite control protein A (CcpA). Initially we characterized …

On The Immunological Roles Of Tlt2 And Hsh2, R Glenn King

All ETDs from UAB

The evolution of multicellular organisms necessitated the ability to detect and remove harmful parasitic microorganisms from the host. This simple requirement for self non-self discrimination has evolved in vertebrates into an elaborate system consisting of a variety of effector mechanisms to perform this process. The immune system is often described as consisting of two distinct yet complimentary components, the innate and adaptive immune systems. It is now recognized that the immune system relies on the highly coordinated interplay between a variety of cell types which cooperate to maintain the health of the organism. The work outlined in this dissertation addresses …

The Effect Of The Aml1-Eto Translocation On Cell Cycle Tumor Suppressor Gene Function, Rose Marie Ko

All ETDs from UAB

The t(8;21)(q22;q22) AML1-ETO translocation is one of the most frequent translocations in acute myeloid leukemia (AML), occurring in approximately 12% of cases. Our laboratory has generated a mouse model in which AML1-ETO is expressed in hematopoietic progenitor cells using a retroviral vector and assayed using bone marrow transplantation. Animals transplanted with AML1-ETO-expressing cells failed to develop leukemia. However, AML1-ETO promoted significant expansion of immature myeloid cells suggesting a “pre-leukemic” state that requires secondary mutations for disease progression. In addition, analysis of cell cycle kinetics in AML1-ETOexpressing myeloid progenitor cells showed that AML1- ETO slowed G1 to S phase progression compared …

Mcmv Induced Cerebellar Maldevelopment, Thadeus B. Koontz

All ETDs from UAB

Congenital Human Cytomegalovirus (HCMV) infection represents a significant cause of morbidity and mortality in infants and children. While most of the systemic damage incurred by the infant in the course of the infection resolves without permanent consequence, the pathological manifestations of infection in the central nervous system (CNS) are often permanent. Children born with congenital HCMV infection may exhibit hearing loss and cognitive impairment in various degrees. These neurological disabilities are correlated with pathological findings in various permutations including infection of the inner ear, ventricular calcifications, ventriculomegaly, microgyria, lissencephaly, and cerebellar hypoplasia. To develop a therapeutic or preventive strategy, HCMV …