Digital Commons Network^™

Microevolution Of Capsule Synthesis Genes Contributes To Pneumococcal Capsule Diversity, Melissa Beth Oliver

All ETDs from UAB

Streptococcus pneumoniae (pneumococcus) is an important human pathogen that expresses a capsular polysaccharide (PS) to shield underlying antigenic structures from complement-mediated opsonophagocytosis. Thus, capsular PS is the major virulence factor, the target of primary immune responses to pneumococcal infections, and the antigenic component of pneumococcal vaccines. Pneumococci have diverse capsular PS synthesis (cps) loci and express over 90 different capsule types. Such diversity helps pneumococci escape immune detection and adapt to changing environments. Recombination of cps genes has been recognized as the main driver of capsule diversity. However, we show point mutations in cps genes encoding glycosyltransferases can broaden enzymes' …

Sulindac Sulfide Amide As A Novel Agent For The Prevention And Treatment Of Lung Cancer, Evrim Gurpinar

All ETDs from UAB

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac sulfide (SS) have shown promising antineoplastic activity in multiple tumor types, but toxicities resulting from cyclooxygenase (COX) inhibition limit their use in cancer prevention. We recently described a N,N-dimethylethyl amine derivative of SS, sulindac sulfide amide (SSA), that does not inhibit COX-1 or -2, yet displays potent tumor cell growth inhibitory activity. Here, we studied the basis for the growth inhibitory effects of SSA on human lung adenocarcinoma cell lines and evaluated its preclinical pharmacology. SSA potently inhibited the growth of lung tumor cells with IC50 values of 2-5 μ compared with 44-52 …

Therapeutic Potential Of Genetically-Engineered Mesenchymal Stem Cells In Multiple Myeloma, Jerome T. Higgs

All ETDs from UAB

ABSTRACT Multiple Myeloma (MM) remains the second most common hematologic malig-nancy occurring in adults, which primarily affects the skeletal system causing severe bone destruction, spinal cord compression and hypercalcemia. Current therapies, which include chemotherapy, radiotherapy, autologouos stem cell transplantation and in some cases surgery, have extended the median survival between 3 and 10 years. However, MM is still incurable and therefore improving current therapies or developing newer ones to reduce the burden of osteolytic damage and extend survival rate will be highly beneficial for patient management. The long-term goal of this study is to develop a novel therapeutic approach to …

Determinant Of G-Chain Mediated Fc Receptor Signaling, Spandan Shah

All ETDs from UAB

Fc receptors provide an interface between humoral immunity and cellular immunity by binding to the Fc portion of immunoglobulin and mediating effector functions. Cells expressing Fc receptors play a major role in immune complex clearance via phagocytosis, leading to a context dependent pro- or anti-inflammatory environment. Signaling by multi-chain Fc receptor complexes, including FcgRI, FcgRIII, FceRI and FcaRI is mediated by the ITAM-containing common FceRIg (g-chain) subunit. However, despite the use of a common g-chain, different Fc receptor complexes elicit specific cellular programs, suggesting additional layers of regulation of tyrosine based signaling by g-chain. We hypothesized that the unique g-chain …

The Effect Of Exogenous Leptin On Dendritic Cell Migration And Interactions With T Cells, Amanda L. Gonzales

Open Access Theses & Dissertations

Obesity is a complex, chronic disease that has reached epidemic proportions in the United States and shows no indication of receding. It is a state of chronic low-grade inflammation that is initiated by morphological changes in large accumulations of adipose tissue. Leptin is a pleiotropic hormone secreted by adipose tissue, presenting a possible link between obesity and inflammation. In this study, we assessed the effect of leptin on bone marrow-derived (BM) dendritic cells (DC) (BM-DC) function, antigen presenting cells vital for the activation of naí¯ve T cells. Previous data produced in our laboratory established that the addition of leptin to …

The Mesocorticolimbic Dopamine Pathway Reconstituted In Vitro: Glutamate Receptors And Corticosteroid-Methamphetamine Neurotoxicity, Jennifer N. Berry

Theses and Dissertations--Psychology

Stress promotes the use of methamphetamine and other recreational substances and is often implicated in relapse to stimulant use. Thus, it is of critical importance to examine the consequences of the co-occurance of stress and methamphetamine use. Activity of the glutamatergic N-methyl D-aspartate (NMDA) receptor system appears to be involved in the neurotoxic effects of both chronic stress and methamphetamine exposure. The current studies investigated the hypothesis that chronic pre-exposure to the stress hormone corticosterone (CORT) results in an increase of NMDA receptor activity and that this will potentiate the neurotoxic effects of methamphetamine (METH). Co-cultures of the …

Alpha-Synuclein Aggregates Activate The Nlrp3 Inflammasome Following Vesicle Rupture, Rudy Orlando Cedillos

Master's Theses

Parkinson's disease (PD) and related synucleinopathies are progressive neurodegenerative disorders that feature the accumulation of intracellular inclusions known as Lewy bodies (LBs) in the brain. The presynaptic protein α-synuclein is the primary constituent of LBs and has been documented to play a major role in the pathogenesis of synucleinopathies. Recently, aggregated α-synuclein has been implicated in prompting microglia-mediated inflammation, a process associated with the progression of neuronal death in neurodegenerative disorders. Although the mechanisms surrounding the induction of neuroinflammation are not well understood, the recently discovered inflammasome-forming NLR proteins have emerged as regulators of inflammation. In this study, we sought …

P900: A Putative Novel Erp Component That Indexes Counter-Measure Use In The P300-Based Concealed Information Test, John B. Meixner Jr., Elena Labkovsky, J. Peter Rosenfeld, Michael R. Winograd, Michael Winograd, Alexander Sokolovsky, Jeff Weishaar, Tim Ullmann

Scholarly Works

Countermeasures pose a serious threat to the effectiveness of the Concealed Information Test (CIT). In a CIT experiment, Rosenfeld and Labkovsky in Psychophysiology 47(6):1002–1010, (2010) observed a previously unknown positive ERP component at about 900 ms poststimulus at Fz and Cz that could potentially serve as an index of countermeasure use. Here, we explored the hypothesis that this component, termed P900, occurs in response to a signal that no further specific response is required in a trial, and could thus appear in countermeasure users that respond differentially depending on the stimulus that appears. In the present experiments, subjects viewed four …

The Incidence And Aetiology Of Hospitalised Community-Acquired Pneumonia Among Vietnamese Adults: A Prospective Surveillance In Central Vietnam, Kensuke Takahashi, Motoi Suzuki, Le Minh, Nguyen Anh, Luu Thi Huong, Tran Vo Son, Phan Long, Nguyen Thi Ai, Le Tho, Konosuke Morimoto, Paul E. Kilgore, Dang Anh, Koya Ariyoshi, Lay Yoshida

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Lower respiratory tract infection (LRTI) including Community-acquired pneumonia (CAP) is a common infectious disease that is associated with significant morbidity and mortality. The patterns of aetiological pathogens differ by region and country. Special attention must be paid to CAP in Southeast Asia (SEA), a region facing rapid demographic transition. Estimates burden and aetiological patterns of CAP are essential for the clinical and public health management. The purposes of the study are to determine the incidence, aetiological pathogens, clinical pictures and risk factors of community-acquired pneumonia (CAP) in the Vietnamese adult population.

Methods

A prospective surveillance for hospitalised adult …

Characterization Of Brer Interaction With The Bile Response Promoters Breab And Brer In Vibrio Cholerae, Francisca A. Cerda-Maira, Gabriela Kovacikova, Brooke A. Jude, Karen Skorupski, Ronald Taylor

Dartmouth Scholarship

The Vibrio cholerae BreR protein is a transcriptional repressor of the breAB efflux system operon, which encodes proteins involved in bile resistance. In a previous study (F. A. Cerda-Maira, C. S. Ringelberg, and R. K. Taylor, J. Bacteriol. 190:7441-7452, 2008), we used gel mobility shift assays to determine that BreR binds at two independent binding sites at the breAB promoter and a single site at its own promoter. Here it is shown, by DNase I footprinting and site-directed mutagenesis, that BreR is able to bind at a distal and a proximal site in the breAB promoter. However, only one of …

Ethanol Diverts Early Neuronal Differentiation Trajectory Of Embryonic Stem Cells By Disrupting The Balance Of Lineage Specifiers., Rosa Sánchez-Alvarez, Saurabh Gayen, Rajanikanth Vadigepalli, Helen Anni

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Ethanol is a toxin responsible for the neurodevelopmental deficits of Fetal Alcohol Spectrum Disorders (FASD). Recent evidence suggests that ethanol modulates the protein expression of lineage specifier transcription factors Oct4 (Pou5f1) and Sox2 in early stages of mouse embryonic stem (ES) cell differentiation. We hypothesized that ethanol induced an imbalance in the expression of Oct4 and Sox2 in early differentiation, that dysregulated the expression of associated and target genes and signaling molecules and diverted cells from neuroectodermal (NE) formation.

METHODOLOGY/PRINCIPAL FINDINGS: We showed modulation by ethanol of 33 genes during ES cell differentiation, using high throughput microfluidic dynamic array …

The Contributions Of Hif-Target Genes To Tumor Growth In Rcc., Ting Zhang, Xiaohua Niu, Lili Liao, Eun-Ah Cho, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Somatic mutations or loss of expression of tumor suppressor VHL happen in the vast majority of clear cell Renal Cell Carcinoma, and it's causal for kidney cancer development. Without VHL, constitutively active transcription factor HIF is strongly oncogenic and is essential for tumor growth. However, the contribution of individual HIF-responsive genes to tumor growth is not well understood. In this study we examined the contribution of important HIF-responsive genes such as VEGF, CCND1, ANGPTL4, EGLN3, ENO2, GLUT1 and IGFBP3 to tumor growth in a xenograft model using immune-compromised nude mice. We found that the suppression of VEGF or CCND1 impaired …

Proteolytic Processing Of The Amyloid Precursor Protein During Apoptosis And Cell Cycle: Implications For Alzheimer's Disease, Tina N. Fiorelli

USF Tampa Graduate Theses and Dissertations

Alzheimer's disease is characterized by the presence of amyloid plaques, made up primarily of Aϐ peptides, and neurofibrillary tangles, containing hyperphosphorylated tau. Aϐ is generated by sequential proteolysis of the amyloid precursor protein (APP) by beta and gamma secretases. The leading hypothesis of Alzheimer's disease pathogenesis is the amyloid cascade hypothesis, which suggests that amyloid is central to the disease process. However, tau pathology correlates more closely with cognitive dysfunction and follows a predictable anatomical course through the brain. We hypothesize that if Aϐ is upstream of tau pathology and tau pathology follows this predictable course through the brain, Aϐ …

Scfslimb Ubiquitin Ligase Suppresses Condensin Ii–Mediated Nuclear Reorganization By Degrading Cap-H2, Daniel W. Buster, Scott G. Daniel, Huy Q. Nguyen, Sarah L. Windler, Lara C. Skwarek, Maureen Peterson

Dartmouth Scholarship

Condensin complexes play vital roles in chromosome condensation during mitosis and meiosis. Condensin II uniquely localizes to chromatin throughout the cell cycle and, in addition to its mitotic duties, modulates chromosome organization and gene expression during interphase. Mitotic condensin activity is regulated by phosphorylation, but mechanisms that regulate condensin II during interphase are unclear. Here, we report that condensin II is inactivated when its subunit Cap-H2 is targeted for degradation by the SCF(Slimb) ubiquitin ligase complex and that disruption of this process dramatically changed interphase chromatin organization. Inhibition of SCF(Slimb) function reorganized interphase chromosomes into dense, compact domains and disrupted …

Attachment Ability And Melanoma Inhibitory Activity Mrna Expression Level Changes In Murine B16-F10 Melanoma Cells Post Nanosecond Electric Pulses, Hongxia Jia

Theses and Dissertations in Biomedical Sciences

The effects of high-voltage nanosecond electric pulses (nsEPs) on metastatic melanoma are still unclear. Hence, we applied one, two, three, and four 300 ns 40 kV/cm pulses to murine B16-F10 melanoma cells. Cell attachment ability was determined by comparing the number of floating cells and the percentage of attached cells. Melanoma inhibitory activity (MIA) is a secretory protein that is highly correlated with the malignancy and metastasis of malignant melanomas. We used MIA as our target to evaluate the effect of nsEPs on metastasis. Pulsed (experimental) and unpulsed (control) cells were incubated at 37°C under a 5% CO₂ atmosphere. …

Pax3 Expression, Protein Modifications And Downstream Target Gene Profiling In Melanocytes And Melanoma Cells, Danielle Bartlett

Theses: Doctorates and Masters

PAX3 is a transcription factor. It plays a major role in the development of melanocytes in the embryo. As a result of alternative splicing, the gene gives rise to eight different transcripts which encode proteins that have differing structures and are therefore likely to activate different downstream target genes. The presence of post-translational modifications has also been shown to alter the functions of the proteins.

PAX3 regulates the maintenance of undifferentiated melanoblasts and mediates pathways involved in proliferation, migration and survival. It has been shown to be expressed in melanoblasts, adult melanocytes, naevi and in most melanoma cells. This implies …

Acute Hypersensitivity Of Pluripotent Testicular Cancer-Derived Embryonal Carcinoma To Low-Dose 5-Aza Deoxycytidine Is Associated With Global Dna Damage-Associated P53 Activation, Anti-Pluripotency And Dna Demethylation, Bijesh K. Biswal, Maroun J. Beyrouthy, Mary P. Hever-Jardine, David Armstrong, Craig R. Tomlinson, Brock C. Christensen, Carmen J. Marsit, Michael J. Spinella

Dartmouth Scholarship

Human embryonal carcinoma (EC) cells are the stem cells of nonseminoma testicular germ cells tumors (TGCTs) and share remarkable similarities to human embryonic stem (ES) cells. In prior work we found that EC cells are hypersensitive to low nanomolar doses of 5-aza deoxycytidine (5-aza) and that this hypersensitivity partially depended on unusually high levels of the DNA methyltransferase, DNMT3B. We show here that low-dose 5-aza treatment results in DNA damage and induction of p53 in NT2/D1 cells. In addition, low-dose 5-aza results in global and gene specific promoter DNA hypomethylation. Low- dose 5-aza induces a p53 transcriptional signature distinct from …

Luteolin Inhibits Human Prostate Tumor Growth By Suppressing Vascular Endothelial Growth Factor Receptor 2-Mediated Angiogenesis, Poyil Pratheeshkumar, Young-Ok Son, Amit Budhraja, Xin Wang, Songze Ding, Lei Wang, Andrew Hitron, Jeong-Chae Lee, Donghern Kim, Sasidharan Padmaja Divya, Gang Chen, Zhuo Zhang, Jia Luo, Xianglin Shi

Toxicology and Cancer Biology Faculty Publications

Angiogenesis, the formation of new blood vessels from pre-existing vascular beds, is essential for tumor growth, invasion, and metastasis. Luteolin is a common dietary flavonoid found in fruits and vegetables. We studied the antiangiogenic activity of luteolin using in vitro, ex vivo, and in vivo models. In vitro studies using rat aortic ring assay showed that luteolin at non-toxic concentrations significantly inhibited microvessel sprouting and proliferation, migration, invasion and tube formation of endothelial cells, which are key events in the process of angiogenesis. Luteolin also inhibited ex vivo angiogenesis as revealed by chicken egg chorioallantoic membrane assay (CAM) …

Targeted Disruption Of Adamts16 Gene In A Rat Genetic Model Of Hypertension, Kathirvel Gopalakrishnan, Sivarajan Kumarasamy, Shakila Abdul-Majeed, Andrea L. Kalinoski, Eric E. Morgan, Amira F. Gohara, Surya M. Nauli, Wanda E. Filipiak, Thomas L. Saunders, Bina Joe

Pharmacy Faculty Articles and Research

A disintegrin-like metalloproteinase with thrombospondin motifs-16 (Adamts16) is an important candidate gene for hypertension. The goal of the present study was to further assess the candidacy of Adamts16 by targeted disruption of this gene in a rat genetic model of hypertension. A rat model was generated by manipulating the genome of the Dahl Salt-sensitive (S) rat using zinc-finger nucleases, wherein the mutant rat had a 17 bp deletion in the first exon of Adamts16, introducing a stop codon in the transcript. Systolic blood pressure (BP) of the homozygous Adamts16(mutant) rats was lower by 36 mmHg compared with the BP of …

Depletion Of Endothelial Or Smooth Muscle Cell-Specific Angiotensin Ii Type 1a Receptors Does Not Influence Aortic Aneurysms Or Atherosclerosis In Ldl Receptor Deficient Mice, Debra L. Rateri, Jessica J. Moorleghen, Victoria Knight, Anju Balakrishnan, Deborah A. Howatt, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Whole body genetic deletion of AT1a receptors in mice uniformly reduces hypercholesterolemia and angiotensin II-(AngII) induced atherosclerosis and abdominal aortic aneurysms (AAAs). However, the role of AT1a receptor stimulation of principal cell types resident in the arterial wall remains undefined. Therefore, the aim of this study was to determine whether deletion of AT1a receptors in either endothelial cells or smooth muscle cells influences the development of atherosclerosis and AAAs.

METHODOLOGY/PRINCIPAL FINDINGS: AT1a receptor floxed mice were developed in an LDL receptor -/- background. To generate endothelial or smooth muscle cell specific deficiency, AT1a receptor floxed mice were bred with …

A Beginning Education In The Anatomy And Function Of The Human Visual Apparatus For Grades 2-4, Evan Andrews

Honors Theses

The human visual apparatus is a remarkable feat of evolution that is nearly a complete mystery to many in the general population. Introducing such a challenging topic is difficult, but, if done in an enjoyable and interactive way to a young audience, the eye can become exciting instead of confusing. The primary objective of this project was to create a short lesson for elementary school students that gave an understanding of the eye's basic anatomy and functions. A fast-paced, interactive format was decided on that included units on the major eye components; color vision and how it can be affected; …

Molecular Characterization Of A Tetraspanin From The Human Liver Fluke, Opisthorchis Viverrini, Supawadee Piratae, Smarn Tesana, Malcolm K. Jones, Paul J. Brindley, Alex Loukas, Erica Lovas, Veerachai Eursitthichai, Banchob Sripa, Sirikanda Thanasuwan, Thewarach Laha

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

The human liver fluke, Opisthorchis viverrini, is designated as a group 1 carcinogen, and is the major risk factor for cholangiocarcinoma in endemic countries throughout Southeast Asia. Proteins in the excretory-secretory products and tegumental surface membranes of the fluke have been proposed to play pivotal roles in parasite survival in the host, and subsequent pathogenesis. These macromolecules are therefore valid targets for the development of vaccines and new drugs to control the infection. Tetraspanins (TSP) are prominent components of the tegument of blood flukes where they are essential for tegument formation, are directly exposed to the immune system, …

Characterization Of Beryllium As A Novel Agent To Study Cell Cycle Arrest And Cellular Senescence, Priyatham Gorjala

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cancer cells evade senescence, apoptosis, and other constraints on proliferation, often via mutation of the p53 tumor suppressor gene (TP53). Normal human lung fibroblasts have been shown to enter premature senescence upon exposure to beryllium. In these cells, BeSO₄ stabilizes p53 protein, increases p21 gene expression, induces senescence-associated β-galactosidase activity and causes cell proliferation arrest. In the present study, we have investigated whether BeSO₄ is able to induce similar effects in cancer cells that have wildtype p53. We have demonstrated that beryllium salt at low concentration can induce molecular changes in the p53 signaling pathway leading to cell …

Hematopoietic Stem Cell Threshold Sensing Controls Regulatory Pathways Facilitating Clinically Relevant Ex Vivo Expansion For Stem Cell Transplantation, Andrew D. Lasiter

Theses and Dissertations (ETD)

The ex vivo expansion of hematopoietic stem cells (HSCs) for transplantation has threefold importance: 1.) First, because of the rarity of stem cells there often isn’t a sufficient supply obtainable from common sources for larger children and adults. 2.) Secondly, patient morbidity and time to hematopoietic reconstitution following myeloablative preconditioning is improved by administering a larger pool of HSCs. 3.) Lastly, gene therapies for hematological diseases still require a robust supply of HSCs to offset varying degrees of inefficiency in vector mediated transfection protocols. These reasons, and others, have been an impetus for many discoveries made within four primary subdivisions …

Anti-Apoptotic Mcl-1 Localizes To The Mitochondrial Matrix And Couples Mitochondrial Fusion To Respiration, Rhonda Perciavalle

Theses and Dissertations (ETD)

MCL-1, an anti-apoptotic BCL-2 family member that is essential for the survival of multiple cell lineages, is also among the most highly amplified genes in cancer. Although MCL-1 is known to oppose cell death, precisely how it functions to promote survival of normal and malignant cells is poorly understood. Here, I report that different forms of MCL-1 reside in distinct mitochondrial locations and exhibit separable functions. On the outer mitochondrial membrane, a MCL-1 isoform acts like other anti-apoptotic BCL-2 molecules to antagonize apoptosis, whereas an amino-terminally truncated isoform of MCL-1 that is imported into the mitochondrial matrix is necessary to …

Glutaredoxin 2 (Grx2) Knockout Increases Sensitivity To Oxidative Stress In Mouse Lens Epithelial Cells, Hongli Wu, Liren Lin, Frank Giblin, Ye-Sheh Ho, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin belongs to the oxidoreductase family with cytosolic glutaredoxin 1 (Grx1) and mitochondrial gluraredoxin 2 (Grx2) isoforms. Of the two isozymes, the function of Grx2 is not well understood. This paper studied the effect of Grx2 deletion on cellular function using primary lens epithelial cell cultures isolated from Grx2 gene knockout (KO) and wild type (WT) mice. We found that both cell types showed similar growth patterns and morphology, and comparable mitochondrial glutathione pool and complex I activity. Cells with deleted Grx2 did not show affected Grx1 or thioredoxin (Trx) expression but exhibited high sensitivity to oxidative stress. Under treatment …

The Role Of Bip Nucleotide Exchange Factor Sil1 In Immunoglobulin Biosynthesis, Tyler Sanford

Theses and Dissertations (ETD)

BiP is an essential endoplasmic reticulum resident molecular chaperone of the HSP70 family that binds exposed hydrophobic regions of unfolded proteins. Substrates bound by BiP are protected from dangerous non-specific interaction with other unfolded proteins via their aggregation prone exposed hydrophobic regions, which are normally buried in the native state, and act as BiP binding targets. For these substrates to mature into the native state, BiP must be released. Like all HSP70 family members, cycles of BiP binding and release are nucleotide dependent and facilitated by two genres of cochaperones, HSP40s, and nucleotide exchange factors (NEFs). HSP40s function in stimulating …

Muc4 And Muc1 Expression In Adenocarcinoma Of The Stomach Correlates With Vessel Invasion And Lymph Node Metastasis: An Immunohistochemical Study Of Early Gastric Cancer., Yukihiro Tamura, Michiyo Higashi, Sho Kitamoto, Seiya Yokoyama, Masahiko Osako, Michiko Horinouchi, Takeshi Shimizu, Mineo Tabata, Surinder K. Batra, Masamichi Goto, Suguru Yonezawa

Journal Articles: Biochemistry & Molecular Biology

We have previously reported that MUC4 expression is a poor prognostic factor in various carcinomas. Our previous study also showed that MUC1 expression in gastric cancers, including the early and advanced stages is a poor prognostic factor. In the present study, the expression profiles of MUC4 and MUC1 were examined by immunohistochemistry (IHC) using two anti-MUC4 monoclonal antibodies (MAbs), 8G7 and 1G8, and anti-MUC1 MAb DF3 in 104 gastrectomy specimens of early gastric adenocarcinoma with submucosal invasion (pT1b2), including 197 histological subtype lesions. Before the IHC study of the human specimens, we evaluated the specificity of the two MAbs by …

Multifactorial Patterns Of Gene Expression In Colonic Epithelial Cells Predict Disease Phenotypes In Experimental Colitis, Aubrey Leigh Frantz, Maria E. C. Bruno, Eric William Rogier, Halide Tuna, Donald A. Cohen, Subbarao Bondada, Ralph Lakshman Chelvarajan, J. Anthony Brandon, C. Darrell Jennings, Charlotte S. Kaetzel

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background— The pathogenesis of inflammatory bowel disease (IBD) is complex and the need to identify molecular biomarkers is critical. Epithelial cells play a central role in maintaining intestinal homeostasis. We previously identified five “signature” biomarkers in colonic epithelial cells (CEC) that are predictive of disease phenotype in Crohn's disease. Here we investigate the ability of CEC biomarkers to define the mechanism and severity of intestinal inflammation.

Methods— We analyzed the expression of RelA, A20, pIgR, tumor necrosis factor (TNF), and macrophage inflammatory protein (MIP)-2 in CEC of mice with dextran sodium sulfate (DSS) acute colitis or T-cell-mediated chronic colitis. …

Gene Expression Analysis Of A Murine Model With Pulmonary Vascular Remodeling Compared To End-Stage Ipah Lungs, Kayoko Shimodaira, Yoichiro Okubo, Eri Ochiai, Haruo Nakayama, Harutaka Katano, Megumi Wakayama, Minoru Shinozaki, Takao Ishiwatari, Daisuke Sasai, Naobumi Tochigi, Tetsuo Nemoto, Tsutomu Saji, Katsuhiko Kamei, Kazutoshi Shibuya

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) continues to be one of the most serious intractable diseases that might start with activation of several triggers representing the genetic susceptibility of a patient. To elucidate what essentially contributes to the onset and progression of IPAH, we investigated factors playing an important role in IPAH by searching discrepant or controversial expression patterns between our murine model and those previously published for human IPAH. We employed the mouse model, which induced muscularization of pulmonary artery leading to hypertension by repeated intratracheal injection of Stachybotrys chartarum, a member of nonpathogenic and ubiquitous fungus in our …