Medicine and Health Sciences Commons^™

Gender Differences In Urothelial Bladder Cancer: Effects Of Natural Killer Lymphocyte Immunity, Charles T. Lutz, Lydia Livas, Steven R. Presnell, Morgan Sexton, Peng Wang

Pathology and Laboratory Medicine Faculty Publications

Men are more likely to develop cancer than women. In fact, male predominance is one of the most consistent cancer epidemiology findings. Additionally, men have a poorer prognosis and an increased risk of secondary malignancies compared to women. These differences have been investigated in order to better understand cancer and to better treat both men and women. In this review, we discuss factors that may cause this gender difference, focusing on urothelial bladder cancer (UBC) pathogenesis. We consider physiological factors that may cause higher male cancer rates, including differences in X chromosome gene expression. We discuss how androgens may promote …

B Lymphocytes Are Required During The Early Priming Of Cd4+ T Cells For Clearance Of Pneumocystis Infection In Mice, Michael M. Opata, Melissa L. Hollifield, Frances E. Lund, Troy D. Randall, Robert Dunn, Beth A. Garvy, David J. Feola

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B cells play a critical role in the clearance of Pneumocystis. In addition to production of Pneumocystis-specific Abs, B cells are required during the priming phase for CD4⁺ T cells to expand normally and generate memory. Clearance of Pneumocystis was found to be dependent on Ag specific B cells and on the ability of B cells to secrete Pneumocystis-specific Ab, as mice with B cells defective in these functions or with a restricted BCR were unable to control Pneumocystis infection. Because Pneumocystis-specific antiserum was only able to partially protect B cell–deficient mice from infection, we …

Enhancing Immunomodulation On Innate Immunity By Shape Transition Among Rna Triangle, Square And Pentagon Nanovehicles, Emil F. Khisamutdinov, Hui Li, Daniel L. Jasinski, Jiao Chen, Jian Fu, Peixuan Guo

Center for Research on Environmental Disease Faculty Publications

Modulation of immune response is important in cancer immunotherapy, vaccine adjuvant development and inflammatory or immune disease therapy. Here we report the development of new immunomodulators via control of shape transition among RNA triangle, square and pentagon. Changing one RNA strand in polygons automatically induced the stretching of the interior angle from 60° to 90° or 108°, resulting in self-assembly of elegant RNA triangles, squares and pentagons. When immunological adjuvants were incorporated, their immunomodulation effect for cytokine TNF-α and IL-6 induction was greatly enhanced in vitro and in animals up to 100-fold, while RNA polygon controls induced unnoticeable effect. The …

Sarcopenia, Obesity, And Natural Killer Cell Immune Senescence In Aging: Altered Cytokine Levels As A Common Mechanism, Charles T. Lutz, Lebris S. Quinn

Pathology and Laboratory Medicine Faculty Publications

Human aging is characterized by both physical and physiological frailty. A key feature of frailty, sarcopenia is the age-associated decline in skeletal muscle mass, strength, and endurance that characterize even the healthy elderly. Increases in adiposity, particularly in visceral adipose tissue, are almost universal in aging individuals and can contribute to sarcopenia and insulin resistance by increasing levels of inflammatory cytokines known collectively as adipokines. Aging also is associated with declines in adaptive and innate immunity, known as immune senescence, which are risk factors for cancer and all-cause mortality. The cytokine interleukin-15 (IL-15) is highly expressed in skeletal muscle tissue …

Crosstalk Between Gastrointestinal Epithelial Cells And Resident Microbiota Promotes Immune Homeostasis, Eric William Rogier

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

The gastrointestinal tract houses one of the most dense and diverse communities of bacteria on the planet. The mutualistic relationship between the host and commensal microbe permits the microbe an ideal environment to grow and provides the host with increased caloric intake, maturation of the adaptive immune system, and resistance against invading pathogens. To maintain a system in which both parties benefit, the epithelium has evolved numerous strategies to ensure epithelial cells respond to microbes appropriately and that potentially hazardous commensals remain distanced from the soma proper. Breakdown of these propitiating mechanisms elicits unchecked inflammation and can lead to pathology …

Manganese Superoxide Dismutase: Guardian Of The Powerhouse, Aaron K. Holley, Vasudevan Bakthavatchalu, Joyce M. Velez-Roman, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

The mitochondrion is vital for many metabolic pathways in the cell, contributing all or important constituent enzymes for diverse functions such as β-oxidation of fatty acids, the urea cycle, the citric acid cycle, and ATP synthesis. The mitochondrion is also a major site of reactive oxygen species (ROS) production in the cell. Aberrant production of mitochondrial ROS can have dramatic effects on cellular function, in part, due to oxidative modification of key metabolic proteins localized in the mitochondrion. The cell is equipped with myriad antioxidant enzyme systems to combat deleterious ROS production in mitochondria, with the mitochondrial antioxidant enzyme manganese …

Sequential Alterations In Catabolic And Anabolic Gene Expression Parallel Pathological Changes During Progression Of Monoiodoacetate-Induced Arthritis, Jin Nam, Priyangi Perera, Jie Liu, Bjoern Rath, James Deschner, Robert Gassner, Timothy A. Butterfield, Sudha Agarwal

Physical Therapy Faculty Publications

Chronic inflammation is one of the major causes of cartilage destruction in osteoarthritis. Here, we systematically analyzed the changes in gene expression associated with the progression of cartilage destruction in monoiodoacetate-induced arthritis (MIA) of the rat knee. Sprague Dawley female rats were given intra-articular injection of monoiodoacetate in the knee. The progression of MIA was monitored macroscopically, microscopically and by micro-computed tomography. Grade 1 damage was observed by day 5 post-monoiodoacetate injection, progressively increasing to Grade 2 by day 9, and to Grade 3-3.5 by day 21. Affymetrix GeneChip was utilized to analyze the transcriptome-wide changes in gene expression, and …

Increased Mitochondrial Calcium Sensitivity And Abnormal Expression Of Innate Immunity Genes Precede Dopaminergic Defects In Pink1-Deficient Mice, Ravi S. Akundi, Zhenyu Huang, Joshua Eason, Jignesh D. Pandya, Lianteng Zhi, Wayne A. Cass, Patrick G. Sullivan, Hansruedi Büeler

Neuroscience Faculty Publications

BACKGROUND: PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca²⁺ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson's disease (PD) display altered activity in the nigrostriatal system of Pink1⁻/⁻ mice.

METHODS AND FINDINGS: Purified brain mitochondria of ^Pink1⁻/⁻ mice showed impaired Ca²⁺ storage capacity, resulting in increased Ca²⁺ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. …

Characterization Of The Equine 2'-5' Oligoadenylate Synthetase 1 (Oas1) And Ribonuclease L (Rnasel) Innate Immunity Genes, Jonathan J. Rios, Andrey A. Perelygin, Maureen T. Long, Teri L. Lear, Andrey A. Zharkikh, Margo A. Brinton, David L. Adelson

Veterinary Science Faculty Publications

BACKGROUND: The mammalian OAS/RNASEL pathway plays an important role in antiviral host defense. A premature stop-codon within the murine Oas1b gene results in the increased susceptibility of mice to a number of flaviviruses, including West Nile virus (WNV). Mutations in either the OAS1 or RNASEL genes may also modulate the outcome of WNV-induced disease or other viral infections in horses. Polymorphisms in the human OAS gene cluster have been previously utilized for case-control analysis of virus-induced disease in humans. No polymorphisms have yet been identified in either the equine OAS1 or RNASEL genes for use in similar case-control studies.

RESULTS: …

Comparative Analysis Of Vertebrate Eif2ak2 (Pkr) Genes And Assignment Of The Equine Gene To Eca15q24-Q25 And The Bovine Gene To Bta11q12-Q15, Andrey A. Perelygin, Teri L. Lear, Andrey A. Zharkikh, Margo A Brinton

Veterinary Science Faculty Publications

The structures of the canine, rabbit, bovine and equine EIF2AK2 genes were determined. Each of these genes has a 5' non-coding exon as well as 15 coding exons. All of the canine, bovine and equine EIF2AK2 introns have consensus donor and acceptor splice sites. In the equine EIF2AK2 gene, a unique single nucleotide polymorphism that encoded a Tyr329Cys substitution was detected. Regulatory elements predicted in the promoter region were conserved in ungulates, primates, rodents, Afrotheria (elephant) and Insectifora (shrew). Western clawed frog and fugu EIF2AK2 gene sequences were detected in the USCS Genome Browser and compared to those of other …