Digital Commons Network^™

Cardio-Metabolic Benefits Of Plant-Based Diets., Hana Kahleova, Susan Levin, Neal Barnard

Medicine Faculty Publications

Cardio-metabolic disease, namely ischemic heart disease, stroke, obesity, and type 2 diabetes, represent substantial health and economic burdens. Almost one half of cardio-metabolic deaths in the U.S. might be prevented through proper nutrition. Plant-based (vegetarian and vegan) diets are an effective strategy for improving nutrient intake. At the same time, they are associated with decreased all-cause mortality and decreased risk of obesity, type 2 diabetes, and coronary heart disease. Evidence suggests that plant-based diets may reduce the risk of coronary heart disease events by an estimated 40% and the risk of cerebral vascular disease events by 29%. These diets also …

Targeting Hepatic Heparin-Binding Egf-Like Growth Factor (Hb-Egf) Induces Anti-Hyperlipidemia Leading To Reduction Of Angiotensin Ii-Induced Aneurysm Development, Seonwook Kim, Lihua Yang, Seongu Kim, Richard G. Lee, Mark J. Graham, Judith A. Berliner, Aldons J. Lusis, Lei Cai, Ryan E. Temel, Debra L. Rateri, Sangderk Lee

Saha Cardiovascular Research Center Faculty Publications

Objective

The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model.

Approach and results

Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks. To induce aneurysm, the mice were fed a high fat diet (22% fat, 0.2% cholesterol; w/w) at 5 week point of ASO administration and infused with angiotensin …

Burden Of Arrhythmias In Epilepsy Patients: A Nationwide Inpatient Analysis Of 1.4 Million Hospitalizations In The United States, Rupak Desai, Chintan Rupareliya, Upenkumar Patel, Syeda Naqvi, Smit Patel, Abhishek Lunagariya, Zabeen Mahuwala

Neurology Faculty Publications

Arrhythmias have been one of the common complications in epilepsy patients and have also been the reason for death. However, limited data exist about the burden and outcomes of arrhythmias by subtypes in epilepsy. Our study aims at evaluating the burden and differences in outcomes of various subtypes of arrhythmias in epilepsy patient population. The Nationwide Inpatient Sample (NIS) database from 2014 was examined for epilepsy and arrhythmias related discharges using appropriate International Classification of Disease, Ninth Revision Clinical Modification (ICD-9-CM) codes. The frequency of arrhythmias, gender differences in arrhythmia by subtypes, in-hospital outcomes and mortality predictors was analyzed. A …

The Role Of Sodium Bicarbonate In The Management Of Some Toxic Ingestions, Aibek E. Mirrakhimov, Taha Ayach, Aram Barbaryan, Goutham Talari, Romil Chadha, Adam Gray

Internal Medicine Faculty Publications

Adverse reactions to commonly prescribed medications and to substances of abuse may result in severe toxicity associated with increased morbidity and mortality. According to the Center for Disease Control, in 2013, at least 2113 human fatalities attributed to poisonings occurred in the United States of America. In this article, we review the data regarding the impact of systemic sodium bicarbonate administration in the management of certain poisonings including sodium channel blocker toxicities, salicylate overdose, and ingestion of some toxic alcohols and in various pharmacological toxicities. Based on the available literature and empiric experience, the administration of sodium bicarbonate appears to …

The Oral Microbiome And Adverse Pregnancy Outcomes., Charles M. Cobb, Patricia J. Kelly, Karen B. Williams, Shilpa Babbar, Mubashir Angolkar, Richard J. Derman

Department of Obstetrics and Gynecology Faculty Papers

Significant evidence supports an association between periodontal pathogenic bacteria and preterm birth and preeclampsia. The virulence properties assigned to specific oral pathogenic bacteria, for example, Fusobacterium nucleatum, Porphyromonas gingivalis, Filifactor alocis, Campylobacter rectus, and others, render them as potential collaborators in adverse outcomes of pregnancy. Several pathways have been suggested for this association: 1) hematogenous spread (bacteremia) of periodontal pathogens; 2) hematogenous spread of multiple mediators of inflammation that are generated by the host and/or fetal immune response to pathogenic bacteria; and 3) the possibility of oral microbial pathogen transmission, with subsequent colonization, in the vaginal microbiome resulting from sexual …

Combining Magnetic Resonance Spectroscopy And Magnetic Resonance Imaging In Diagnosing Focal Brain Lesions In Children, Farah Naz Farid, Waseem Mirza, Nauman Hashmani

Section of Ophthalmology

Introduction: We attempted to find the sensitivity and specificity of various pediatric brain masses in the Pakistani population while keeping histopathology or clinical diagnosis as the gold standard.
Methods: This was a retrospective study that was conducted from January 2007 to January 2016. We reviewed the records of 204 patients that presented to the radiology department of Aga Khan University Hospital (AKUH). Out of the 204, 135 pediatric patients in the 0–18 age group with focal brain lesions who underwent magnetic resonance spectroscopy (MRS) and a biopsy or clinical diagnosis were included. If histopathology was available, it was taken as …

Stromal Cyclin D1 Promotes Heterotypic Immune Signaling And Breast Cancer Growth, Timothy G. Pestell, Xuanmao Jiao, Mukesh Kumar, Amy R. Peck, Marco Prisco, Shengqiong Deng, Zhiping Li, Adam Ertel, Matthew C. Casimiro, Xiaoming Ju, Agnese Di Rocco, Gabriele Di Sante, Sanjay Katiyar, Alison Shupp, Michael P. Lisanti, Pooja Jain, Kongming Wu, Hallgeir Rui, Douglas Craig Hooper, Zuoren Yu, Aaron R. Goldman, David W. Speicher, Lisa Laury-Kleintop, Richard G. Pestell

Department of Cancer Biology Faculty Papers

The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that drives cell autonomous cell cycle progression and proliferation. Herein we show cyclin D1 abundance is increased > 30-fold in the stromal fibroblasts of patients with invasive breast cancer, associated with poor outcome. Cyclin D1 transformed hTERT human fibroblast to a cancer-associated fibroblast phenotype. Stromal fibroblast expression of cyclin D1 (cyclin D1^Stroma) in vivo, enhanced breast epithelial cancer tumor growth, restrained apoptosis, and increased autophagy. Cyclin D1^Stroma had profound effects on the breast tumor microenvironment increasing the recruitment of F4/80⁺ and CD11b⁺ macrophages and increasing …

Relative Contribution Of Porcine Reproductive And Respiratory Syndrome Virus Open Reading Frames 2–4 To The Induction Of Protective Immunity, Katherine Kimpston-Burkgren, Ignacio Correas, Fernando A. Osorio, David Steffen, Asit K. Pattnaik, Ying Fang, Hiep L. X. Vu

Nebraska Center for Virology: Faculty Publications

The minor glycoproteins (GPs) of PRRSV, GP2, GP3, and GP4, form a heterotrimer that is required for viral infectivity, presumably due to its interaction with the key cellular receptor CD163. These 3 GPs are encoded by open reading frames (ORFs) 2a, 3, and 4 (herein referred to as ORFs 2–4), respectively. The goal of this study was to investigate the immunogenicity of the PRRSV-2 minor GPs. Through the use of reverse genetics, a chimeric virus (designated SDFL24) was constructed by replacing ORFs 2–4 of the PRRSV-1 strain SD01-08 with the corresponding genes of the PRRSV-2 strain FL12. While the parental …

Structure-Based Design Of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses To A Conserved Epitope, Brian G. Pierce, Elisabeth N. Boucher, Kurt H. Piepenbrink, Monir Ejemal, Chelsea A. Rapp, William D. Thomas Jr, Eric J. Sundberg, Zhiping Weng, Yang Wang

Food for Health: Publications

Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as …

Proximal Femur Locking Plate For Sub-Trochanteric Femur Fractures: Factors Associated With Failure, Akbar Zubairi, Rizwan Haroon Rashid, Marij Zahid, Pervaiz Mahmood Hashmi, Shahryar Noordin

Section of Orthopaedic Surgery

Introduction: Proximal femur locking compression plates (PF-LCP) have gained popularity since their inception due to superior biomechanical stability and durability but clinical experience has shown conflicting results including implant failure.
Objective: To study the incidence of implant failure in patients with sub-trochanteric fractures managed with proximal femoral locking compression plate and identify potential risk factors associated with the failure.
Materials & Methods: Fifty patients with sub-trochanteric fractures, operated upon with titanium PF-LCP were included in the study from January 2012 to December 2014. These plates were of two designs including one five 5.0 mm proximal locking screws (implant A) and …

Brain Microvascular Injury And White Matter Disease Provoked By Diabetes-Associated Hyperamylinemia, Han Ly, Nirmal Verma, Fengen Wu, Miao Liu, Kathryn E. Saatman, Peter T. Nelson, John T. Slevin, Larry B. Goldstein, Geert Jan Biessels, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

OBJECTIVE: The brain blood vessels of patients with type 2 diabetes and dementia have deposition of amylin, an amyloidogenic hormone cosecreted with insulin. It is not known whether vascular amylin deposition is a consequence or a trigger of vascular injury. We tested the hypothesis that the vascular amylin deposits cause endothelial dysfunction and microvascular injury and are modulated by amylin transport in the brain via plasma apolipoproteins.

METHODS: Rats overexpressing amyloidogenic (human) amylin in the pancreas (HIP rats) and amylin knockout (AKO) rats intravenously infused with aggregated amylin were used for in vivo phenotyping. We also carried out biochemical analyses …

A Retrospective Review Of Paediatric Head Injuries In Asia - A Pan Asian Trauma Outcomes Study (Patos) Collaboration, Shu-Ling Chong, Uzma R. Khan, Indumathy Santhanam, Jun Seok Seo, Quan Wang, Sabariah Faizah Jamaluddin,, Quoc Ai Hoang Quoc, Su Yah Chew, Marcus Eng Hock Ong

Department of Emergency Medicine

Objective: We aim to examine the mechanisms of head-injured children presenting to participating centres in the Pan Asian Trauma Outcomes Study (PATOS) and to evaluate the association between mechanism of injury and severe outcomes.
Design and Setting: We performed a retrospective review of medical records among emergency departments (EDs) of eight PATOS centres, from September 2014 - August 2015.
Participants: We included children <16 years old who presented within 24 hours of head injury and were admitted for observation or required a computed tomography (CT) of the brain from the ED. We excluded children with known coagulopathies, neurological co-morbidities or prior neurosurgery. We reviewed the mechanism, intent, location and object involved in each injury, and the patients' physical findings on presentation.
Outcomes: Primary outcomes were death, endotracheal intubation or neurosurgical intervention. Secondary outcomes included hospital and ED length of stay.
Results: 1438 children were analysed. 953 children (66.3%) were male and the median age was 5.0 years (IQR …

A Naturally Generated Decoy Of The Prostate Apoptosis Response-4 Protein Overcomes Therapy Resistance In Tumors, Nikhil Hebbar, Ravshan Burikhanov, Nidhi Shukla, Shirley Qiu, Yanming Zhao, Kojo S. J. Elenitoba-Johnson, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

Primary tumors are often heterogeneous, composed of therapy-sensitive and emerging therapy-resistant cancer cells. Interestingly, treatment of therapy-sensitive tumors in heterogeneous tumor microenvironments results in apoptosis of therapy-resistant tumors. In this study, we identify a prostate apoptosis response-4 (Par-4) amino-terminal fragment (PAF) that is released by diverse therapy-sensitive cancer cells following therapy-induced caspase cleavage of the tumor suppressor Par-4 protein. PAF caused apoptosis in cancer cells resistant to therapy and inhibited tumor growth. A VASA segment of Par-4 mediated its binding and degradation by the ubiquitin ligase Fbxo45, resulting in loss of Par-4 proapoptotic function. Conversely, PAF, which contains this VASA …

Hypomethylation Of Cntfrα Is Associated With Proliferation And Poor Prognosis In Lower Grade Gliomas., Kun Fan, Xiaowen Wang, Jingwen Zhang, Romela Irene Ramos, Haibo Zhang, Chunjie Li, Dan Ye, Jiansheng Kang, Diego M Marzese, Dave S B Hoon, Wei Hua

Articles, Abstracts, and Reports

Ciliary neurotrophic factor receptor α subunit (CNTFRα) and CNTF play important roles in neuron survival, glial differentiation and brain tumor growth. However, the molecular mechanisms of CNTFRα regulation and its clinical significance in glioma remain largely unknown. Here, we found CNTFRα was overexpressed in lower grade gliomas (LGG) compared with glioblastoma (GBM) and normal brain specimens in TCGA datasets and in an independent cohort. Bioinformatics analysis revealed a CpG shore of the CNTFRα gene regulated its mRNA expression in TCGA datasets. This observation was further validated with clinical specimens and functionally verified using demethylating agents. Additionally, we observed that independent …

3-Aryl-4h-Chromene-4-Ones As Antineoplastic Agents For The Treatment Of Cancer, Svitlana P. Bondarenko, Mykhaylo S. Frasinyuk, Chunming Liu, David S. Watt

Markey Cancer Center Faculty Patents

Isoflavonoids or pharmaceutically acceptable salts thereof or pharmaceutically acceptable compositions thereof for the treatment of prostate cancer or for the treatment or inhibition of prostate cancer metastasis in a patient in need thereof are disclosed.

The Impact Of Smoking On Sentinel Node Metastasis Of Primary Cutaneous Melanoma., Maris S Jones, Peter C Jones, Stacey L Stern, David Elashoff, Dave S B Hoon, John Thompson, Nicola Mozzillo, Omgo E Nieweg, Dirk Noyes, Harald J Hoekstra, Jonathan S Zager, Daniel F Roses, Alessandro Testori, Brendon J Coventry, Mark B Smithers, Robert Andtbacka, Doreen Agnese, Erwin Schultz, Eddy C Hsueh, Mark Kelley, Schlomo Schneebaum, Lisa Jacobs, Tawnya Bowles, Mohammed Kashani-Sabet, Douglas Johnson, Mark B Faries

Articles, Abstracts, and Reports

BACKGROUND: Although a well-established causative relationship exists between smoking and several epithelial cancers, the association of smoking with metastatic progression in melanoma is not well studied. We hypothesized that smokers would be at increased risk for melanoma metastasis as assessed by sentinel lymph node (SLN) biopsy.

METHODS: Data from the first international Multicenter Selective Lymphadenectomy Trial (MSLT-I) and the screening-phase of the second trial (MSLT-II) were analyzed to determine the association of smoking with clinicopathologic variables and SLN metastasis.

RESULTS: Current smoking was strongly associated with SLN metastasis (p = 0.004), even after adjusting for other predictors of metastasis. Among …

First-In-Human Clinical Trial Of Oral Onc201 In Patients With Refractory Solid Tumors, Mark N. Stein, Joseph R. Bertino, Howard L. Kaufman, Tina M. Mayer, Rebecca A. Moss, Ann W. Silk, Nancy Chan, Jyoti Malhotra, Loma Rodriguez, Joseph Aisner, Robert Aiken, Bruce G. Haffty, Robert S. Dipaola, Tracie Saunders, Andrew Zloza, Sherri Damare, Yasmeen Beckett, Bangning Yu, Saltanat Najmi, Christian Gabel, Sioghan Dickerson, Ling Zheng, Wafik S. El-Deiry, Joshua E. Allen, Martin Stogniew, Wolfgang Oster, Janice M. Mehnert

Internal Medicine Faculty Publications

Purpose: ONC201 is a small-molecule selective antagonist of the G protein–coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D).

Experimental Design: This open-label study treated 10 patients during dose escalation with histologically confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design. An additional 18 patients were treated at the RP2D in an expansion phase to collect additional safety, …

Pro-Angiogenesis Therapy And Aging: A Mini-Review, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Apart from major illnesses and chronic afflictions, the elderly experience lesser ailments, such as muscle weakness, cold intolerance, and transient memory lapses. Physical signs in the aged include wrinkled skin and the slow healing of skin abrasions. These ailments and signs are grouped together because they may be due in part to an age-linked, waning microcirculation. A reduced capillary density (CD) throughout the body of aged people and animals has been reported in over 40 papers. The reduced CD is due in turn to declining levels of angiogenic growth factors (AGFs) throughout the body during old age, as documented in …

Understanding Safe Sleep Knowledge And Practices Among New Mexico Clinical Staff, Theresa H. Cruz, Emily A. Lilo, Sahlea Tubbeh

Reports & Documents

The objective of this study was to gain a better understanding of current safe sleep practices implemented by nurses, and demonstrated to families, in the infant-oriented units [e.g., the Neonatal Intensive Care Units (NICU), Mother-Baby Units, and Labor and Delivery] of Albuquerque hospitals. The University of New Mexico Prevention Research Center (UNM PRC) also used data from the survey to inform a training session for clinical staff. The training was based on the most recent guidelines from the American Academy of Pediatrics (AAP) on safe sleep, applied in a culturally appropriate context for staff and for staff to use with …

Biomechanical Testing Of An Exercise For Strengthening The Proximal Femur., Alyssa Osbourne

Electronic Theses and Dissertations

Based on the principles of cutting edge bone remodeling research, a unique therapeutic exercise device was designed specifically to improve bone quality at the most critical location of the proximal femur prone to fracture: the superior-lateral femoral neck where the fracture first initiates during a fall. The exercise/device is intended to work by inducing enough strain in the bone to stimulate the body’s natural bone remodeling mechanisms to increase bone density in the proximal femur and consequently prevent a fracture from arising if a fall to the side does occur.

In order to test the proposed exercise, experiments simulating the …

Custom Software For The 3d Printing Of Patient Specific Plate Bending Templates In Pelvic Fracture Repair., Gordon B Lents

Electronic Theses and Dissertations

The purpose of this work is to reduce the operative time and blood loss incurred during open reduction and internal fixation (ORIF) of traumatic pelvic injuries through the creation of patient specific bending templates for reconstruction plates. These templates are 3D printed in a resin capable of being sterilized and taken into the operating room so that bending may be performed by the surgeon before the patient is opened or by another team member in parallel with the surgeon.

A novel software extension was created in 3D modeling software to allow a surgeon to individually position screws on a pelvic …

Effects Of Acute Sepsis On Renal Structure And Sympathetic Innervation In Mice, Tuqa Alkhateeb

Electronic Theses and Dissertations

Sympathetic nerves are important for renal physiology and sepsis pathophysiology. A recent study showed sprouting of sympathetic nerves in spleen of septic mice. This study was done to test if renal sprouting of sympathetic nerves also happens and to investigate renal morphology in septic mice. Cecal ligation and puncture (CLP) was used to induce sepsis and kidneys were removed for evaluation. Bowman’s space was diminished with cortical bubble cells present suggestive of acute renal pathology, however, renal function was unchanged. Acute sepsis did not affect either renal sympathetic innervation or non-neuronal cholinergic cells. Mouse kidneys had more epinephrine (EPI) than …

A Tnf-Jnk-Axl-Erk Signaling Axis Mediates Primary Resistance To Egfr Inhibition In Glioblastoma., Gao Guo, Ke Gong, Sonia Ali, Neha Ali, Shahzad Shallwani, Kimmo J Hatanpaa, Edward Pan, Bruce Mickey, Sandeep Burma, David H Wang, Santosh Kesari, Jann N Sarkaria, Dawen Zhao, Amyn A Habib

Articles, Abstracts, and Reports

Aberrant epidermal growth factor receptor (EGFR) signaling is widespread in cancer, making the EGFR an important target for therapy. EGFR gene amplification and mutation are common in glioblastoma (GBM), but EGFR inhibition has not been effective in treating this tumor. Here we propose that primary resistance to EGFR inhibition in glioma cells results from a rapid compensatory response to EGFR inhibition that mediates cell survival. We show that in glioma cells expressing either EGFR wild type or the mutant EGFRvIII, EGFR inhibition triggers a rapid adaptive response driven by increased tumor necrosis factor (TNF) secretion, which leads to activation in …

Improving Nk Cell Therapy For Osteosarcoma, Jennifer Foltz

Dissertations and Theses (Open Access)

Osteosarcoma (OS) is the most common primary bone tumor. Despite new treatment options, 5-year survival for metastatic OS has remained at only 30% for the last 30 years. Adoptive transfer of Natural Killer (NK) cells holds promise for a new, non-toxic therapy for OS. NK cells are part of the innate immune system and readily kill metastatic and chemotherapy-resistant OS in vitro and in murine models. However, there is little data regarding their efficacy in animal models with an intact immune system. In addition, the OS tumor microenvironment is highly suppressive, producing TGFβ which impedes NK cell killing of solid …

Improvements In Four-Dimensional And Dual Energy Computed To Mography, Rachael M. Martin

Dissertations and Theses (Open Access)

Dual energy and 4D computed tomography (CT) seek to address some of the limitations in traditional CT imaging. Dual energy CT, among other purposes, allows for the quantification and improved visualization of contrast materials, and 4D CT is often used in radiation therapy applications as it allows for the visualization and quantification of object motion. While much research has been done with these technologies, areas remain for potential improvement, both in preclinical and clinical settings, which will be explored in this dissertation. Preclinical dual energy cone-beam CT (CBCT) can benefit from wider separation between the peak energy of the two …

In Vivo Evaluation Of Stem Cell Aggregates On Osteochondral Regeneration., Banupriya Sridharan, Amy D. Laflin, Michael A. Holtz, Donna M. Pacicca, Nicholas K. Wischmeier, Michael S. Detamore

Manuscripts, Articles, Book Chapters and Other Papers

To date, many osteochondral regenerative approaches have utilized varied combinations of biocompatible materials and cells to engineer cartilage. Even in cell-based approaches, to date, no study has utilized stem cell aggregates alone for regenerating articular cartilage. Thus, the purpose of this study was to evaluate the performance of a novel stem cell-based aggregate approach in a fibrin carrier to regenerate osteochondral defects in the Sprague-Dawley rat trochlear groove model. Two different densities of rat bone marrow mesenchymal stem cell (rBMSC) aggregates were fabricated by the hanging drop technique. At 8 weeks, the cell aggregates supported the defects and served as …

Towards A Personalized Cancer Gene Therapy: A Case Of Clear Cell Renal Cell Carcinoma, Dumitru Iacobas, Sanda Iacobas

NYMC Faculty Publications

No abstract provided.

Myo-Inositol Reduces Β-Catenin Activation In Colitis, Emily M. Bradford, Corey A. Thompson, Tatiana Goretsky, Guang-Yu Yang, Luz M. Rodriguez, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

AIM

To assess dietary myo-inositol in reducing stem cell activation in colitis, and validate pβ-catenin^S552 as a biomarker of recurrent dysplasia.

METHODS

We examined the effects of dietary myo-inositol treatment on inflammation, pβ-catenin^S552 and pAkt levels by histology and western blot in IL-10^-/- and dextran sodium sulfate-treated colitic mice. Additionally, we assessed nuclear pβ-catenin^S552 in patients treated with myo-inositol in a clinical trial, and in patients with and without a history of colitis-induced dysplasia.

RESULTS

In mice, pβ-catenin^S552 staining faithfully reported the effects of myo-inositol in reducing inflammation and intestinal stem cell activation. In a …

De Novo Triiodothyronine Formation From Thyrocytes Activated By Thyroid-Stimulating Hormone, Cintia E. Citterio, Balaji Veluswamy, Sarah J. Morgan, Valerie A. Galton, J. Paul Banga, Stephen Atkins, Yoshiaki Morishita, Susanne Neumann, Rauf Latif, Marvin C. Gershengorn, Terry J. Smith, Peter Arvan

Pharmacy Faculty Articles and Research

The thyroid gland secretes primarily tetraiodothyronine (T₄), and some triiodothyronine (T₃). Under normal physiological circumstances, only one-fifth of circulating T₃ is directly released by the thyroid, but in states of hyperactivation of thyroid-stimulating hormone receptors (TSHRs), patients develop a syndrome of relative T₃ toxicosis. Thyroidal T₄ production results from iodination of thyroglobulin (TG) at residues Tyr⁵ and Tyr¹³⁰, whereas thyroidal T₃ production may originate in several different ways. In this study, the data demonstrate that within the carboxyl-terminal portion of mouse TG, T₃ is formed …

Mobilization Studies In Mice Deficient In Sphingosine Kinase 2 Support A Crucial Role Of The Plasma Level Of Sphingosine-1-Phosphate In The Egress Of Hematopoietic Stem Progenitor Cells, Mateusz Adamiak, Lakshman Chelvarajan, Kevin R. Lynch, Webster L. Santos, Ahmed Abdel-Latif, Mariusz Z. Ratajczak

Gill Heart & Vascular Institute Faculty Publications

Sphingosine-1-phosphate (S1P) is a bioactive lipid involved in cell signaling and, if released from cells, also plays a crucial role in regulating the trafficking of lympho-hematopoietic cells, including primitive hematopoietic stem/progenitor cells (HSPCs). It has been demonstrated that S1P chemoattracts HSPCs, and its level in peripheral blood creates a gradient directing egress of these cells during mobilization. In this paper we analyzed hematopoiesis in mice deficient in sphingosine kinase 2 (Sphk2-KO mice) and studied the effect of this mutation on plasma S1P levels. We found that Sphk2-KO mice have normal hematopoiesis, and, in contrast to Sphk1-KO mice, the circulating S1P …