Medicine and Health Sciences Commons^™

Role Of Hla-I Structural Variants And The Polyreactive Antibodies They Generate In Immune Homeostasis, Mepur H Ravindranath, Fatiha El Hilali, Carly J Amato-Menker, Hajar El Hilali, Senthamil R Selvan, Edward J Filippone

Department of Medicine Faculty Papers

Cell-surface HLA-I molecules consisting of β2-microglobulin (β2m) associated heavy chains (HCs), referred to as Face-1, primarily present peptides to CD8+ T-cells. HCs consist of three α-domains, with selected amino acid sequences shared by all alleles of all six isoforms. The cell-surface HLA undergoes changes upon activation by pathological conditions with the expression of β2m-free HCs (Face-2) resulting in exposure of β2m-masked sequences shared by almost all alleles and the generation of HLA-polyreactive antibodies (Abs) against them. Face-2 may homodimerize or heterodimerize with the same (Face-3) or different alleles (Face-4) preventing exposure of shared epitopes. Non-allo immunized males naturally carry HLA-polyreactive …

Four Faces Of Cell-Surface Hla Class-I: Their Antigenic And Immunogenic Divergence Generating Novel Targets For Vaccines, Mepur H Ravindranath, Narendranath M Ravindranath, Senthamil R Selvan, Edward J Filippone, Carly J Amato-Menker, Fatiha El Hilali

Department of Medicine Faculty Papers

Leukocyte cell-surface HLA-I molecules, involved in antigen presentation of peptides to CD8+ T-cells, consist of a heavy chain (HC) non-covalently linked to β2-microglobulin (β2m) (Face-1). The HC amino acid composition varies across all six isoforms of HLA-I, while that of β2m remains the same. Each HLA-allele differs in one or more amino acid sequences on the HC α1 and α2 helices, while several sequences among the three helices are conserved. HCs without β2m (Face-2) are also observed on human cells activated by malignancy, viral transformation, and cytokine or chemokine-mediated inflammation. In the absence of β2m, the monomeric Face-2 exposes immunogenic …

Which Sample Type Is Better For Xpert Mtb/Rif To Diagnose Adult And Pediatric Pulmonary Tuberculosis?, Mengyuan Lyu, Jian Zhou, Yuhui Cheng, Weelic Chong, Kang Wu, Teng Fang, Tianbo Fu, Binwu Ying

Department of Medicine Faculty Papers

OBJECTIVE: This review aimed to identify proper respiratory-related sample types for adult and pediatric pulmonary tuberculosis (PTB), respectively, by comparing performance of Xpert MTB/RIF when using bronchoalveolar lavage (BAL), induced sputum (IS), expectorated sputum (ES), nasopharyngeal aspirates (NPAs), and gastric aspiration (GA) as sample.

METHODS: Articles were searched in Web of Science, PubMed, and Ovid from inception up to 29 June 2020. Pooled sensitivity and specificity were calculated, each with a 95% confidence interval (CI). Quality assessment and heterogeneity evaluation across included studies were performed.

RESULTS: A total of 50 articles were included. The respective sensitivity and specificity were 87% …

Epigenetic Regulation Of Tumor Suppressors By Helicobacter Pylori Enhances Ebv-Induced Proliferation Of Gastric Epithelial Cells, Saurabh Pandey, Hem Chandra Jha, Sanket Kumar Shukla, Meghan K. Shirley, Erle S. Robertson

Department of Medicine Faculty Papers

Helicobacter pylori and Epstein-Barr virus (EBV) are two well-known contributors to cancer and can establish lifelong persistent infection in the host. This leads to chronic inflammation, which also contributes to development of cancer. Association with H. pylori increases the risk of gastric carcinoma, and coexistence with EBV enhances proliferation of infected cells. Further, H. pylori-EBV coinfection causes chronic inflammation in pediatric patients. We have established an H. pylori-EBV coinfection model system using human gastric epithelial cells. We showed that H. pylori infection can increase the oncogenic phenotype of EBV-infected cells and that the cytotoxin-associated gene (CagA) protein encoded by H. …

Allometry And Ecology Of The Bilaterian Gut Microbiome., Scott Sherrill-Mix, Kevin Mccormick, Abigail Lauder, Aubrey Bailey, Laurie Zimmerman, Yingying Li, Jean-Bosco N Django, Paco Bertolani, Christelle Colin, John A Hart, Terese B Hart, Alexander V Georgiev, Crickette M Sanz, David B Morgan, Rebeca Atencia, Debby Cox, Martin N Muller, Volker Sommer, Alexander K Piel, Fiona A Stewart, Sheri Speede, Joe Roman, Gary Wu, Josh Taylor, Rudolf Bohm, Heather M Rose, John Carlson, Deus Mjungu, Paul Schmidt, Celeste Gaughan, Joyslin I Bushman, Ella Schmidt, Kyle Bittinger, Ronald G Collman, Beatrice H Hahn, Frederic D Bushman

Department of Medicine Faculty Papers

Classical ecology provides principles for construction and function of biological communities, but to what extent these apply to the animal-associated microbiota is just beginning to be assessed. Here, we investigated the influence of several well-known ecological principles on animal-associated microbiota by characterizing gut microbial specimens from bilaterally symmetrical animals (

Expression Of Enteropathogenic Escherichia Coli Map Is Significantly Different Than That Of Other Type Iii Secreted Effectors In Vivo., Mai Nguyen, Jason Rizvi, Gail Hecht

Department of Medicine Faculty Papers

The enteropathogenic Escherichia coli (EPEC) locus of enterocyte effacement (LEE)-encoded effectors EspF and Map are multifunctional and have an impact on the tight junction barrier while the non-LEE-encoded proteins NleH1 and NleH2 possess significant anti-inflammatory activity. In order to address the temporal expression of these important genes in vivo, their promoters were cloned upstream of the luxCDABE operon, and luciferase expression was measured in EPEC-infected mice by bioluminescence using an in vivo imaging system (IVIS). Bioluminescent images of living mice, of excised whole intestines, and of whole intestines longitudinally opened and washed were assessed. The majority of bioluminescent bacteria localized …

A Tandem Duplication Within The Fibrillin 1 Gene Is Associated With The Mouse Tight Skin Mutation., Linda D. Siracusa, Rodney Mcgrath, Qing Ma, John J. Moskow, Jayanthi Manne, Paul J. Christner, Arthur M. Buchberg, Sergio A. Jimenez

Department of Medicine Faculty Papers

Mice carrying the Tight skin (Tsk) mutation have thickened skin and visceral fibrosis resulting from an accumulation of extracellular matrix molecules. These and other connective tissue abnormalities have made Tskl + mice models for scleroderma, hereditary emphysema, and myocardial hypertrophy. Previously we localized Tsk to mouse chromosome 2 in a region syntenic with human chromosome 15. The microfibrillar glycoprotein gene, fibrillin 1 (FBN1), on human chromosome 15q, provided a candidate for the Tsk mutation. We now demonstrate that the Tsk chromosome harbors a 30- to 40-kb genomic duplication within the Fbn1 gene that results in a larger than normal in-frame …