Medical Anatomy Commons^™

Ros And Mirna Dysregulation In Ovarian Cancer Development, Angiogenesis And Therapeutic Resistance, David C Stieg, Yifang Wang, Ling-Zhi Liu, Bing-Hua Jiang

Kimmel Cancer Center Faculty Papers

The diverse repertoires of cellular mechanisms that progress certain cancer types are being uncovered by recent research and leading to more effective treatment options. Ovarian cancer (OC) is among the most difficult cancers to treat. OC has limited treatment options, especially for patients diagnosed with late-stage OC. The dysregulation of miRNAs in OC plays a significant role in tumorigenesis through the alteration of a multitude of molecular processes. The development of OC can also be due to the utilization of endogenously derived reactive oxygen species (ROS) by activating signaling pathways such as PI3K/AKT and MAPK. Both miRNAs and ROS are …

A Rare Presentation Of Pericardial Tumor Presenting As Chronic Cough, Swarup Sharma Rijal, William H. Risher, Aakankshya Kharel, Upendra Kaphle

Advances in Clinical Medical Research and Healthcare Delivery

Chronic cough can pose various diagnostic and therapeutic dilemmas to physicians. Airway narrowing secondary to endoluminal disease or extrinsic compression are known etiologies of chronic cough. We report an extremely rare case of chronic cough due to extrinsic airway compression by a large pericardial lipoma with subsequent resolution of symptoms after the resection of the mass. This case provides insight into the rare etiology of chronic cough that is addressable with surgical intervention.

Assessment Of Spatial Skills In Human Anatomy And Physiology Students, Abigail Carroll

Honors Theses

Visual spatial skills are an individual’s ability to mentally and manipulate the shapes, forms and positions of objects. Spatial skills are necessary for adequate learning in many settings. Few studies have assessed spatial skills compared to success in Anatomy and Physiology in undergraduate students. Most students in this course are on a health profession track. Due to the increasing health care demands and need for competent health care professionals, this study assesses the innate spatial skill ability in students and acquired additional learned spatial skills. This study tests 17 students with the paper-folding test, blank page test, and two surveys …

Bacille Calmette-Guérin Vaccine Reprograms Human Neonatal Lipid Metabolism In Vivo And In Vitro, Joann Diray-Arce, Asimenia Angelidou, Kristoffer Jarlov Jensen, Maria Giulia Conti, Rachel S Kelly, Matthew Pettengill, Mark Liu, Simon D Van Haren, Scott D Mcculloch, Greg Michelloti, Olubukola Idoko, Tobias R Kollmann, Beate Kampmann, Hanno Steen, Al Ozonoff, Jessica Lasky-Su, Christine S Benn, Ofer Levy

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Vaccines have generally been developed with limited insight into their molecular impact. While systems vaccinology enables characterization of mechanisms of action, these tools have yet to be applied to infants, who are at high risk of infection and receive the most vaccines. Bacille Calmette-Guérin (BCG) protects infants against disseminated tuberculosis (TB) and TB-unrelated infections via incompletely understood mechanisms. We employ mass-spectrometry-based metabolomics of blood plasma to profile BCG-induced infant responses in Guinea-Bissau in vivo and the US in vitro. BCG-induced lysophosphatidylcholines (LPCs) correlate with both TLR-agonist- and purified protein derivative (PPD, mycobacterial antigen)-induced blood cytokine production in vitro, raising the …

Additive Manufacturing Of Variable Contrast Computed Tomography Anatomical Phantoms Using A Single Feedstock In Fused Filament Fabrication, Cory J. Darling

University of New Orleans Theses and Dissertations

Anatomical phantoms used in biomedical education and training benefit greatly from Fused filament fabrication’s (FFF) ability to rapidly produce complex and unique models. Current materials and methods used in FFF have limited ability to accurately produce phantoms that can mimic the radiological properties of multiple biological tissues. This research demonstrates that the CT contrast of FFF produced models can be modified by varying the concentration of bismuth oxide in acrylonitrile butadiene styrene (ABS) filaments and a tunable CT contrast that mimics the CT contrast ranging from fatty tissue to cortical bone using a single composite filament without introducing artificial image …

Ocular Adnexal Metastases From Renal Cell Carcinoma: An Update And Comprehensive Literature Review, Tejal Magan, Tejus Pradeep, Madalina Tuluc, Jurij R. Bilyk, Tatyana Milman

Wills Eye Hospital Papers

PURPOSE: The purpose of this study was to review the clinical presentation, systemic work-up, and outcomes of all previously reported ocular adnexal (OA) metastases from renal cell carcinoma (RCC). METHODS: This was a literature review. PubMed and Google Scholar databases were searched for all well-documented cases of OA metastases from RCC. RESULTS: Final analysis identified 44 patients with either biopsy-confirmed (41/44, 93%) or treatment response-documented (3/44, 6%) OA metastases from RCC. Thirty-four (77%) patients were male. The median age was 60 years (mean: 60, range: 22-87 years). The most common presenting signs were proptosis (19/44, 43%) and OA mass (14/44, …

Gm1 Ganglioside Modifies Microglial And Neuroinflammatory Responses To Α-Synuclein In The Rat Aav-A53t Α-Synuclein Model Of Parkinson's Disease, Jay S Schneider, Garima Singh, Courtney K. Williams, Vikrant Singh

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Among the pathological events associated with the dopaminergic neurodegeneration characteristic of Parkinson's disease (PD) are the accumulation of toxic forms of α-synuclein and microglial activation associated with neuroinflammation. Although numerous other processes may participate in the pathogenesis of PD, the two factors mentioned above may play critical roles in the initiation and progression of dopamine neuron degeneration in PD. In this study, we employed a slowly progressing model of PD using adeno-associated virus-mediated expression of human A53T α-synuclein into the substantia nigra on one side of the brain and examined the microglial response in the striatum on the injected side …

Medical Manikin Augmented Reality Simulation (M2ars), Pauline Delacruz, Jacob Gibson, Daniel Howard, Jaclyn Peacock, Kendall Robbins

Modeling, Simulation and Visualization Student Capstone Conference

The Medical Manikin Augmented Reality Simulation (M2ARS) is an augmented reality simulation application built for the Microsoft HoloLens 2 that uses the principles of anatomy transfer to overlay human anatomical structures onto a medical manikin digitally. These structures currently consist of the skeletal, muscular, and circulatory systems. In addition, a model of the lungs and an animated heart are also available within the simulation. M2ARS allows the user to view these structures in a manner that is both visually and spatially accurate to the human body. This application contains two modes; an augmented reality mode, which uses a manikin, and …

Patterns Of Crystallin Gene Expression In Differentiation State Specific Regions Of The Embryonic Chicken Lens, Zhiwei Ma, Daniel Chauss, Joshua Disatham, Xiaodong Jiao, Lisa Ann Brennan, A Sue Menko, Marc Kantorow, J Fielding Hejtmancik

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Purpose: Transition from lens epithelial cells to lens fiber cell is accompanied by numerous changes in gene expression critical for lens transparency. We identify expression patterns of highly prevalent genes including ubiquitous and enzyme crystallins in the embryonic day 13 chicken lens.

Methods: Embryonic day 13 chicken lenses were dissected into central epithelial cell (EC), equatorial epithelial cell (EQ), cortical fiber cell (FP), and nuclear fiber cell (FC) compartments. Total RNA was prepared, subjected to high-throughput unidirectional mRNA sequencing, analyzed, mapped to the chicken genome, and functionally grouped.

Results: A total of 77,097 gene-specific transcripts covering 17,450 genes were expressed, …

The Pro-Fibrotic Response Of Mesenchymal Leader Cells To Lens Wounding Involves Hyaluronic Acid, Its Receptor Rhamm, And Vimentin, A. Sue Menko, Alison Romisher, Janice L Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Hyaluronic Acid/Hyaluronan (HA) is a major component of the provisional matrix deposited by cells post-wounding with roles both in regulating cell migration to repair a wound and in promoting a fibrotic outcome to wounding. Both are mediated through its receptors CD44 and RHAMM. We now showed that HA is present in the provisional matrix assembled on the substrate surface in a lens post-cataract surgery explant wound model in which mesenchymal leader cells populate the wound edges to direct migration of the lens epithelium across the adjacent culture substrate onto which this matrix is assembled. Inhibiting HA expression with 4-MU blocked …

68-Year Old Man With Progressive Weakness And Ventilator Dependent Respiratory Failure: A Case Report Of Sporadic Late Onset Nemaline Myopathy, P. Kirupaharan, Daniel Kramer, Alan Gandler, Lawrence C. Kenyon, Ross Summer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Neuromuscular pathologies must be considered when caring for patients with persistent or progressive respiratory failure. Pertinent disease states may involve skeletal muscles of respiration or associated neurologic structures including motor neurons, peripheral neurons and the neuromuscular junction. Diagnosis may require pulmonary function testing, neurophysiologic studies, imaging, and/or muscle biopsy.

Case presentation: A 68-year-old male was transferred to our intensive care unit (ICU) for management of ventilator dependent respiratory failure. Upon further historical review, he described gradually worsening gait instability and muscle weakness, which was previously attributed to vascular Parkinsonism in the setting of known cerebrovascular disease. Upon arrival to …

Uncontrolled Mitochondrial Calcium Uptake Underlies The Pathogenesis Of Neurodegeneration In Micu1-Deficient Mice And Patients, Raghavendra Singh, Adam Bartok, Melanie Paillard, Ashley L. Tyburski, Melanie B Elliott, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Dysregulation of mitochondrial Ca2+ homeostasis has been linked to neurodegenerative diseases. Mitochondrial Ca2+ uptake is mediated via the calcium uniporter complex that is primarily regulated by MICU1, a Ca2+-sensing gatekeeper. Recently, human patients with MICU1 loss-of-function mutations were diagnosed with neuromuscular and cognitive impairments. While studies in patient-derived cells revealed altered mitochondrial calcium signaling, the neuronal pathogenesis was difficult to study. To fill this void, we created a neuron-specific MICU1-KO mouse model. These animals show progressive, abnormal motor and cognitive phenotypes likely caused by the degeneration of motor neurons in the spinal cord and the cortex. We found increased susceptibility …

Fluorescence Imaging Detection Of Nanodomain Redox Signaling Events At Organellar Contacts, David M. Booth, Péter Várnai, Suresh K Joseph, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

This protocol describes how to visualize, detect, and analyze redox signals (oxidative bursts) at the ER-mitochondrial interface. It uses drug-inducible crosslinking to target the genetically encoded glutathione redox sensor Grx1roGFP2 to organellar contact sites to measure local redox changes associated with transient depolarizations of the mitochondrial membrane potential (flickers). The strategy allows imaging of the oxidized to reduced glutathione ratio (GSSG:GSH) in subcellular regions below the diffraction limit with good temporal resolution and minimum phototoxicity. Moreover, the strategy also applies to diverse parameters including pH, H2O2, and Ca2+.

Suppression Of Pi3k Signaling Is Linked To Autophagy Activation And The Spatiotemporal Induction Of The Lens Organelle Free Zone, Rifah Gheyas, Ramon Ortega-Alvarez, Daniel Chauss, Marc Kantorow, A. Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The terminal steps of lens cell differentiation require elimination of all organelles to create a central Organelle Free Zone (OFZ) that is required for lens function of focusing images on the retina. Previous studies show that the spatiotemporal elimination of these organelles during development is autophagy-dependent. We now show that the inhibition of PI3K signaling in lens organ culture results in the premature induction of autophagy within 24 h, including a significant increase in LAMP1+ lysosomes, and the removal of lens organelles from the center of the lens. Specific inhibition of just the PI3K/Akt signaling axis was directly linked to …

Human Endothelial Cells Promote Arsenic-Transformed Lung Epithelial Cells To Induce Tumor Growth And Angiogenesis Through Interleukin-8 Induction, Lei Zhao, Yi-Fang Wang, Jie Liu, Bing-Hua Jiang, Ling-Zhi Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Arsenic exposure is associated with lung cancer. Angiogenesis is essential for tumor development. However, the role and mechanism of human vascular endothelial cells in tumor growth and angiogenesis induced by arsenic-transformed bronchial epithelial (As-T) cells remain to be elucidated. In this study, we found that endothelial cells significantly increased As-T cell-induced tumor growth compared to those induced by As-T cells alone. To understand the molecular mechanism, we found that endothelial cells co-cultured with As-T cells or cultured in conditioned medium (CM) prepared from As-T cells showed much higher cell migration, proliferation, and tube formation compared to those co-cultured with BEAS-2B …

Mir-196a Upregulation Contributes To Gefitinib Resistance Through Inhibiting Gltp Expression, Bing-Jie Liu, Fang-Fang Li, Yun-Xia Xie, Chong-Yuan Fan, Wen-Jing Liu, Jian-Ge Qiu, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Tyrosine kinase inhibitor (TKI) therapy has greatly improved lung cancer survival in patients with epidermal growth factor receptor (EGFR) mutations. However, the development of TKI-acquired resistance is the major problem to be overcome. In this study, we found that miR-196a expression was greatly induced in gefitinib-resistant lung cancer cells. To understand the role and mechanism of miR-196a in TKI resistance, we found that miR-196a-forced expression alone increased cell resistance to gefitinib treatment in vitro and in vivo by inducing cell proliferation and inhibiting cell apoptosis. We identified the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) bound to the …

The Role Of Decorin Proteoglycan In Mitophagy., Thomas Neill, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Proteoglycans are emerging as critical regulators of intracellular catabolism. This rise in prominence has transformed our basic understanding and alerted us to the existence of non-canonical pathways, independent of nutrient deprivation, that potently control the autophagy downstream of a cell surface receptor. As a member of the small leucine-rich proteoglycan gene family, decorin has single-handedly pioneered the connection between extracellular matrix signaling and autophagy regulation. Soluble decorin evokes protracted endothelial cell autophagy via Peg3 and breast carcinoma cell mitophagy via mitostatin by interacting with VEGFR2 or the MET receptor tyrosine kinase, respectively. In this paper, we give a mechanistic perspective …

Reactive Oxygen Species Reprogram Macrophages To Suppress Antitumor Immune Response Through The Exosomal Mir-155-5p/Pd-L1 Pathway, Xiang Li, Shaomin Wang, Wei Mu, Jennifer Barry, Anna Han, Richard L Carpenter, Bing-Hua Jiang, Stephen C Peiper, M G Mahoney, A E Aplin, Hong Ren, Jun He

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Cancer cells have an imbalance in oxidation-reduction (redox) homeostasis. Understanding the precise mechanisms and the impact of the altered redox microenvironment on the immunologic reaction to tumors is limited.

Methods: We isolated exosomes from ovarian cancer cells through ultracentrifuge and characterized by Western-blots and Nanoparticle Tracking Analysis. 2D, 3D-coculture tumor model, and 3D live cell imaging were used to study the interactions between tumor cells, macrophages and CD3 T cells in vitro. The role of exosomal miR-155-5p in tumor growth was evaluated in xenograft nude mice models and immune-competent mice models. Flow cytometry and flow sorting were used to …

Microbial Cell Factory Of Baccatin Iii Preparation In Escherichia Coli By Increasing Dbat Thermostability And In Vivo Acetyl-Coa Supply, Jia-Jun Huang, Tao Wei, Zhi-Wei Ye, Qian-Wang Zheng, Bing-Hua Jiang, Wen-Feng Han, An-Qi Ye, Pei-Yun Han, Li-Qiong Guo, Jun-Fang Lin

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Given the rapid development of genome mining in this decade, the substrate channel of paclitaxel might be identified in the near future. A robust microbial cell factory with gene dbat, encoding a key rate-limiting enzyme 10-deacetylbaccatin III-10-O-transferase (DBAT) in paclitaxel biosynthesis to synthesize the precursor baccatin III, will lay out a promising foundation for paclitaxel de novo synthesis. Here, we integrated gene dbat into the wild-type Escherichia coli BW25113 to construct strain BWD01. Yet, it was relatively unstable in baccatin III synthesis. Mutant gene dbat S189V with improved thermostability was screened out from a semi-rational mutation library …

Opa1 Modulates Mitochondrial Ca 2+ Uptake Through Er-Mitochondria Coupling, Benjamín Cartes-Saavedra, Josefa Macuada, Daniel Lagos, Duxan Arancibia, María E Andrés, Patrick Yu-Wai-Man, György Hajnóczky, Verónica Eisner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Autosomal Dominant Optic Atrophy (ADOA), a disease that causes blindness and other neurological disorders, is linked to OPA1 mutations. OPA1, dependent on its GTPase and GED domains, governs inner mitochondrial membrane (IMM) fusion and cristae organization, which are central to oxidative metabolism. Mitochondrial dynamics and IMM organization have also been implicated in Ca2+ homeostasis and signaling but the specific involvements of OPA1 in Ca2+ dynamics remain to be established. Here we studied the possible outcomes of OPA1 and its ADOA-linked mutations in Ca2+ homeostasis using rescue and overexpression strategies in Opa1-deficient and wild-type murine embryonic fibroblasts (MEFs), respectively and in …