Medicine and Health Sciences Commons^™

Hypoxic Stress Induces, But Cannot Sustain Trophoblast Stem Cell Differentiation To Labyrinthine Placenta Due To Mitochondrial Insufficiency, Yufen Xie, Sichang Zhou, Zhongliang Jiang, Jing Dai, Elizabeth E. Puscheck, Icksoo Lee, Graham Parker, Maik Hüttemann, Daniel A. Rappolee

Department of Obstetrics and Gynecology Research Publications

Dysfunctional stem cell differentiation into placental lineages is associated with gestational diseases. Of the differentiated lineages available to trophoblast stem cells (TSC), elevated O2 and mitochondrial function are necessary to placental lineages at the maternal–placental surface and important in the etiology of preeclampsia. TSC lineage imbalance leads to embryonic failure during uterine implantation. Stress at implantation exacerbates stem cell depletion by decreasing proliferation and increasing differentiation. In an implantation site O2 is normally ~ 2%. In culture, exposure to 2% O2 and fibroblast growth factor 4 (FGF4) enabled the highest mouse TSC multipotency and proliferation. In contrast, hypoxic stress (0.5% …

Mechanisms Of T-B Cell Cooperation Important For Mog Antibody Mediated Demyelination, Dusanka S. Skundric

Neurology Faculty Publications

No abstract provided.

Reduction In Post-Botulinum Toxin Flu-Like Symptoms After Injection With Incobotulinum Toxin, Edwin George, Natalya Shneyder

Neurology Faculty Publications

OBJECTIVE: To determine if patients reporting flu-like symptoms (FLS) after botulinum toxin (BoNT) injections are less susceptible to this reaction after incobotulinum toxin.

BACKGROUND: Approximately 10% of patients injected with BoNT in our clinic complain of FLS, primarily malaise, myalgias and rhinorrhea, beginning a few days to one week after injection and lasting one week or less. A review by Baizabal-Carvallo et al. (Toxicon, 2011, 58:1-7) found rates of FLS between 1.7 and 20% in patients after various preparations of botulinum toxin A, and a subsequent study showed increased cytokines in patients with FLS (Neurotoxicity Research, …

Metabotropic Glutamate Receptor-1 As A Novel Target For The Antiangiogenic Treatment Of Breast Cancer, Cecilia L. Speyer, Ali H. Hachem, Ali A. Assi, Jennifer S. Johnson, John Austin Devries, David H. Gorski

Department of Surgery

Metabotropic glutamate receptors (mGluRs) are normally expressed in the central nervous system, where they mediate neuronal excitability and neurotransmitter release. Certain cancers, including melanoma and gliomas, express various mGluR subtypes that have been implicated as playing a role in disease progression. Recently, we detected metabotropic glutamate receptor-1 (gene: GRM1; protein: mGluR1) in breast cancer and found that it plays a role in the regulation of cell proliferation and tumor growth. In addition to cancer cells, brain endothelial cells express mGluR1. In light of these studies, and because angiogenesis is both a prognostic indicator in cancer correlating with a poorer …

Autoantibodies To Agrin In Myasthenia Gravis Patients, Bin Zhang, Chengyong Shen, Beverly Bealmear, Samia Ragheb, Wen-Cheng Xiong, Richard A. Lewis, Robert P. Lisak, Lin Mei

Immunology and Microbiology Faculty Research Publications

To determine if patients with myasthenia gravis (MG) have antibodies to agrin, a proteoglycan released by motor neurons and is critical for neuromuscular junction (NMJ) formation, we collected serum samples from 93 patients with MG with known status of antibodies to acetylcholine receptor (AChR), muscle specific kinase (MuSK) and lipoprotein-related 4 (LRP4) and samples from control subjects (healthy individuals and individuals with other diseases). Sera were assayed for antibodies to agrin. We found antibodies to agrin in 7 serum samples of MG patients. None of the 25 healthy controls and none of the 55 control neurological patients had agrin antibodies. …

Cone Beam Computertomography (Cbct) In Interventional Chest Medicine – High Feasibility For Endobronchial Real Time Navigation, Wolfgang Hohenforst-Schmidt, Paul Zarogoulidis, Thomas Vogl, J. Francis Turner, Robert Browning, Bernd Linsmeier, Haidong Huang, Qiang Li, Kaid Darwiche, Lutz Freitag, Michael Simoff, Ioannis Kioumis, Konstantinos Zarogoulidis, Johannes Brachmann

Internal Medicine Faculty Publications

Introduction: Currently there are several advanced guiding techniques for pathoanatomical diagnosis of incidental solitary pulmonary nodules (iSPN): Electromagnetic navigation (EMN) with or without endobronchial ultrasound (EBUS) with miniprobe, transthoracic ultrasound (TTUS) for needle approach to the pleural wall and adjacent lung and computed tomography (CT)-guidance for (seldom if ever used) endobronchial or (common) transthoracical approach. In several situations one technique is not enough for efficient diagnosis, therefore we investigated a new diagnostic technique of endobronchial guided biopsies by a Cone Beam Computertomography (CBCT) called DynaCT (SIEMENS AG Forchheim, Germany). Method and Material: In our study 33 incidental solitary pulmonary nodules …

Carp-1 Functional Mimetics Are A Novel Class Of Small Molecule Inhibitors Of Malignant Pleural Mesothelioma Cells, Shazia Jamal, Vino T. Cheriyan, Magesh Muthu, Sara Munie, Edi Levi, Abdelkader E. Ashour, Harvey I. Pass, Anil Wali, Mandip Singh, Arun K. Rishi

Oncology Faculty Publications

Malignant pleural mesothelioma (MPM) is an asbestos-related thoracic malignancy that is characterized by late metastases, and resistance to therapeutic modalities. The toxic side-effects of MPM therapies often limit their clinical effectiveness, thus necessitating development of new agents to effectively treat and manage this disease in clinic. CARP-1 functional mimetics (CFMs) are a novel class of compounds that inhibit growth of diverse cancer cell types. Here we investigated MPM cell growth suppression by the CFMs and the molecular mechanisms involved. CFM-1, -4, and -5 inhibited MPM cell growth, in vitro, in part by stimulating apoptosis. Apoptosis by CFM-4 involved activation of …

Epicatechin Stimulates Mitochondrial Activity And Selectively Sensitizes Cancer Cells To Radiation, Hosam A. Elbaz, Icksoo Lee, Deborah A. Antwih, Jenney Liu, Maik Hüttemann, Steven P. Zielske

Center for Molecular Medicine and Genetics

Radiotherapy is the treatment of choice for solid tumors including pancreatic cancer, but the effectiveness of treatment is limited by radiation resistance. Resistance to chemotherapy or radiotherapy is associated with reduced mitochondrial respiration and drugs that stimulate mitochondrial respiration may decrease radiation resistance. The objectives of this study were to evaluate the potential of (-)-epicatechin to stimulate mitochondrial respiration in cancer cells and to selectively sensitize cancer cells to radiation. We investigated the natural compound (-)-epicatechin for effects on mitochondrial respiration and radiation resistance of pancreatic and glioblastoma cancer cells using a Clark type oxygen electrode, clonogenic survival assays, and …

Radiation Exposure Of Patients By Cone Beam Ct During Endobronchial Navigation - A Phantom Study, Wolfgang Hohenforst-Schmidt, Rosemarie Banckwitz, Paul Zarogoulidis, Thomas Vogl, Kaid Darwiche, Eugene Goldberg, Haidong Huang, Michael Simoff, Qiang Li, Robert Browning, Lutz Freitag, J. Francis Turner, Patrick Le Pivert, Lonny Yarmus, Konstantinos Zarogoulidis, Johannes Brachmann

Internal Medicine Faculty Publications

Rationale: Cone Beam Computed Tomography imaging has become increasingly important in many fields of interventional therapies. Objective: Lung navigation study which is an uncommon soft tissue approach. Methods: As no effective organ radiation dose levels were available for this kind of Cone Beam Computed Tomography application we simulated in our DynaCT (Siemens AG, Forchheim, Germany) suite 2 measurements including 3D acquisition and again for 3D acquisition and 4 endobronchial navigation maneuvers under fluoroscopy towards a nodule after the 8th segmentation in the right upper lobe over a total period of 20 minutes (min). These figures reflect the average complexity and …

Neonatal Encephalopathic Cerebral Injury In South India Assessed By Perinatal Magnetic Resonance Biomarkers And Early Childhood Neurodevelopmental Outcome, Peter J. Lally, David L. Price, Shreela S. Pauliah, Alan Bainbridge, Justin Kurien, Neeraja Sivasamy, Frances M. Cowan, Guhan Balraj, Manjula Ayer, Kariyapilly Satheesan, Sreejith Ceebi, Angie Wade, Ravi Swamy, Shaji Padinjattel, Betty Hutchon, Madhava Vijayakumar, Mohandas Nair, Krishnakumar Padinharath, Hui Zhang, Ernest B. Cady, Seetha Shankaran, Sudhin Thayyil

Department of Pediatrics

Although brain injury after neonatal encephalopathy has been characterised well in high-income countries, little is known about such injury in low- and middle-income countries. Such injury accounts for an estimated 1 million neonatal deaths per year. We used magnetic resonance (MR) biomarkers to characterise perinatal brain injury, and examined early childhood outcomes in South India.

Metabotropic Glutamate Receptor-1 Contributes To Progression In Triple Negative Breast Cancer, Malathi Banda, Cecilia L. Speyer, Sara N. Semma, Kingsley O. Osuala, Nicole Kounalakis, Keila E. Torres Torres, Nicola J. Barnard, Hyunjin J. Kim, Bonnie F. Sloane, Fred R. Miller, James S. Goydos, David H. Gorski

Department of Surgery

TNBC is an aggressive breast cancer subtype that does not express hormone receptors (estrogen and progesterone receptors, ER and PR) or amplified human epidermal growth factor receptor type 2 (HER2), and there currently exist no targeted therapies effective against it. Consequently, finding new molecular targets in triple negative breast cancer (TNBC) is critical to improving patient outcomes. Previously, we have detected the expression of metabotropic glutamate receptor-1 (gene: GRM1; protein: mGluR1) in TNBC and observed that targeting glutamatergic signaling inhibits TNBC growth both in vitro and in vivo. In this study, we explored how mGluR1 contributes to TNBC …

Gold(Iii)-Dithiocarbamato Peptidomimetics In The Forefront Of The Targeted Anticancer Therapy: Preclinical Studies Against Human Breast Neoplasia, Chiara Nardon, Sara M. Schmitt, Huanjie Yang, Jian Zuo, Delores Fregona, Q. Ping Dou

Oncology Faculty Publications

Since the serendipitous discovery of cisplatin, platinum-based drugs have become well-established antitumor agents, despite the fact that their clinical use is limited by many severe side-effects. In order to both improve the chemotherapeutic index and broaden the therapeutic spectrum of current drugs, our most recent anti-neoplastic agents, Au(III) complexes, were designed as carrier-mediated delivery systems exploiting peptide transporters, which are up-regulated in some cancers. Among all, we focused on two compounds and tested them on human MDA-MB-231 (resistant to cisplatin) breast cancer cell cultures and xenografts, discovering the proteasome as a major target both in vitro and in vivo. …