Digital Commons Network^™

Glutamine Supplementation Alleviates Vasculopathy And Corrects Metabolic Profile In An In Vivo Model Of Endothelial Cell Dysfunction., Francesco Addabbo, Qiuying Chen, Dhara P Patel, May Rabadi, Brian Ratliff, Frank Zhang, Jean-Francois Jasmin, Michael Wolin, Michael Lisanti, Steven S Gross, Michael S Goligorsky

Kimmel Cancer Center Faculty Papers

Endothelial Cell Dysfunction (ECD) is a recognized harbinger of a host of chronic cardiovascular diseases. Using a mouse model of ECD triggered by treatment with L-Nω-methylarginine (L-NMMA), we previously demonstrated that renal microvasculature displays a perturbed protein profile, including diminished expression of two key enzymes of the Krebs cycle associated with a Warburg-type suppression of mitochondrial metabolism. We hypothesized that supplementation with L-glutamine (GLN), that can enter the Krebs cycle downstream this enzymatic bottleneck, would normalize vascular function and alleviate mitochondrial dysfunction. To test this hypothesis, mice with chronic L-NMMA-induced ECD were co-treated with GLN at different concentrations for 2 …

A Phase 1b Study Of Humanized Ks-Interleukin-2 (Huks-Il2) Immunocytokine With Cyclophosphamide In Patients With Epcam-Positive Advanced Solid Tumors., Joseph P Connor, Mihaela C Cristea, Nancy L Lewis, Lionel D Lewis, Philip B Komarnitsky, Maria R Mattiacci, Mildred Felder, Sarah Stewart, Josephine Harter, Jean Henslee-Downey, Daniel Kramer, Roland Neugebauer, Roger Stupp

Kimmel Cancer Center Faculty Papers

BACKGROUND: Humanized KS-interleukin-2 (huKS-IL2), an immunocytokine with specificity for epithelial cell adhesion molecule (EpCAM), has demonstrated favorable tolerability and immunologic activity as a single agent.

METHODS: Phase 1b study in patients with EpCAM-positive advanced solid tumors to determine the maximum tolerated dose (MTD) and safety profile of huKS-IL2 in combination with low-dose cyclophosphamide. Treatment consisted of cyclophosphamide (300 mg/m2 on day 1), and escalating doses of huKS-IL2 (0.5-4.0 mg/m2 IV continuous infusion over 4 hours) on days 2, 3, and 4 of each 21-day cycle. Safety, pharmacokinetic profile, immunogenicity, anti-tumor and biologic activity were evaluated.

RESULTS: Twenty-seven patients were treated …

Development Of Frataxin Gene Expression Measures For The Evaluation Of Experimental Treatments In Friedreich's Ataxia., Heather L Plasterer, Eric C Deutsch, Matthew Belmonte, Elizabeth Egan, David R Lynch, James R Rusche

Department of Pediatrics Faculty Papers

BACKGROUND: Friedreich ataxia is a progressive neurodegenerative disorder caused by GAA triplet repeat expansions or point mutations in the FXN gene and, ultimately, a deficiency in the levels of functional frataxin protein. Heterozygous carriers of the expansion express approximately 50% of normal frataxin levels yet manifest no clinical symptoms, suggesting that therapeutic approaches that increase frataxin may be effective even if frataxin is raised only to carrier levels. Small molecule HDAC inhibitor compounds increase frataxin mRNA and protein levels, and have beneficial effects in animal models of FRDA.

METHODOLOGY/PRINCIPAL FINDINGS: To gather data supporting the use of frataxin as a …

Doxorubicin-Induced, Tnf-Α-Mediated Brain Oxidative Stress, Neurochemical Alterations, And Cognitive Decline: Insights Into Mechanisms Of Chemotherapy Induced Cognitive Impairment And Its Prevention, Jeriel T. Keeney

Theses and Dissertations--Chemistry

The works presented in this dissertation provide insights into the mechanisms of chemotherapy-induced cognitive impairment (CICI or “ChemoBrain”) and take steps toward outlining a preventive strategy. CICI is now widely recognized as a complication of cancer chemotherapy experienced by a large percentage of cancer survivors. Approximately fifty percent of existing FDA-approved anti-cancer drugs generate reactive oxygen species (ROS). Doxorubicin (Dox), a prototypical ROS-generating chemotherapeutic agent, produces the reactive superoxide radical anion (O₂^-•) in vivo. Dox treatment results in oxidation of plasma proteins, including ApoA-I, leading to TNF-α-mediated oxidative stress in plasma and brain. TNF-α elevation in brain …

Evaluation Of Echo Ps Positioning System In A Porcine Model Of Simulated Laparoscopic Ventral Hernia Repair, Erin M. Hanna, Guy R. Voeller, J. Scott Roth, Jeffrey R. Scott, Darcy H. Gagne, David A. Iannitti

Surgery Faculty Publications

Purpose. Operative efficiency improvements for laparoscopic ventral hernia repair (LVHR) have focused on reducing operative time while maintaining overall repair efficacy. Our objective was to evaluate procedure time and positioning accuracy of an inflatable mesh positioning device (Echo PS Positioning System), as compared to a standard transfascial suture technique, using a porcine model of simulated LVHR. Methods. The study population consisted of seventeen general surgeons (n = 17) that performed simulated LVHR on seventeen (n = 17) female Yorkshire pigs using two implantation techniques: (1) Ventralight ST Mesh + Echo PS Positioning System (Echo PS) and …

Ezh2 Knockdown Suppresses The Growth And Invasion Of Human Inflammatory Breast Cancer Cells., Zhaomei Mu, Hua Li, Sandra V Fernandez, Katherine R Alpaugh, Rugang Zhang, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

INTRODUCTION: Inflammatory breast cancer (IBC) is the most metastatic variant of breast cancer with the poorest survival in all types of breast cancer patients and presently therapeutic targets for IBC are very limited. Enhancer of zeste homolog 2 (EZH2) is frequently expressed in human IBC and its expression positively correlates with worse clinical outcome. However, the molecular basis for EZH2 promoting IBC has not been explored. Here, we investigated the functional role of EZH2 in IBC cells by examining the effects of its knockdown on the formation of tumor spheroids and invasion of these cells in vitro and in vivo …

Late Developing Mammary Tumors And Hyperplasia Induced By A Low-Oncogenic Variant Of Mouse Mammary Tumor Virus (Mmtv) Express Genes Identical To Those Induced By Canonical Mmtv, Robert D. Bruno

School of Medical Diagnostics & Translational Sciences Publications

Background: The canonical milk-transmitted mouse mammary tumor virus (MMTV) of C3H mice (C3H-MMTV) rapidly induces tumors in 90% of infected animals by 8 months of age. Pro-viral insertions of C3H-MMTV into genomic DNA results in the overexpression of common core insertion site (CIS) genes, including Wnt1/10b, Rspo2, and Fgf3. Conversely, infection by either the endogenous Mtv-1 virus (in C3Hf) or the exogenous nodule-inducing virus (NIV) (in Balb/c NIV) induces premalignant mammary lesions and tumors with reduced incidence and longer latency than C3H-MMTV. Here, we asked whether Mtv-1/NIV affected the expression of core CIS genes.

Findings: We confirmed the presence of …

Tuberculosis Verrucosa Cutis In A Patient With Keloid Over Ear Lobule, Muhammad Sohail Halim, Sadaf Qadeer Ahmed, Montasir Junaid, Muhammad Rizwan Bashir

Section of Otolaryngology, Head & Neck Surgery

Tuberculosis (TB) is a global health problem with predominance in resource-poor countries. Extrapulmonary TB constitutes approximately 10% of the cases and can present as different forms depending on the route of entry. Cutaneous TB is a small subset of the extrapulmonary TB. Cutaneous TB can either be of primary origin or secondary origin or it can be a part of a systemic infection. TB verrucosa cutis (TBVC) is the exogenous reinfection of TB in a previously sensitised patient. Routine cultures do not have a high yield in TBVC due to the paucibacillary nature of the organism. Here we are presenting …

Identification Of Phosphorylation Sites In The Cooh-Terminal Tail Of The Μ-Opioid Receptor., Ying-Ju Chen, Sue Oldfield, Adrian J. Butcher, Andrew B. Tobin, Kunal Saxena, Vsevolod V. Gurevich, Jeffrey L. Benovic, Graeme Henderson, Eamonn Kelly

Department of Biochemistry and Molecular Biology Faculty Papers

Phosphorylation is considered a key event in the signalling and regulation of the μ opioid receptor (MOPr). Here, we used mass spectroscopy to determine the phosphorylation status of the C-terminal tail of the rat MOPr expressed in human embryonic kidney 293 (HEK-293) cells. Under basal conditions, MOPr is phosphorylated on Ser(363) and Thr(370), while in the presence of morphine or [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO), the COOH terminus is phosphorylated at three additional residues, Ser(356) , Thr(357) and Ser(375). Using N-terminal glutathione S transferase (GST) fusion proteins of the cytoplasmic, C-terminal tail of MOPr and point mutations of the same, we …

Presence Of Anaplastic Lymphoma Kinase In Inflammatory Breast Cancer., Fredika M Robertson, Emanuel F Petricoin Iii, Steven J Van Laere, Francois Bertucci, Khoi Chu, Sandra V Fernandez, Zhaomei Mu, Katherine Alpaugh, Jianming Pei, Rita Circo, Julia Wulfkuhle, Zaiming Ye, Kimberly M Boley, Hui Liu, Ricardo Moraes, Xuejun Zhang, Ruggero Demaria, Sanford H Barsky, Guoxian Sun, Massimo Cristofanilli

Department of Medical Oncology Faculty Papers

Although Inflammatory Breast Cancer (IBC) is recognized as the most metastatic variant of locally advanced breast cancer, the molecular basis for the distinct clinical presentation and accelerated program of metastasis of IBC is unknown. Reverse phase protein arrays revealed activation of the receptor tyrosine kinase, anaplastic lymphoma kinase (ALK) and biochemically-linked downstream signaling molecules including JAK1/STAT3, AKT, mTor, PDK1, and AMPKβ in pre-clinical models of IBC. To evaluate the clinical relevance of ALK in IBC, analysis of 25 IBC patient tumors using the FDA approved diagnostic test for ALK genetic abnormalities was performed. These studies revealed that 20/25 (80%) had …

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 …

Using The Theory Of Planned Behavior As A Predictor Of Radiologic Technologists' Use Of Patient Radiation Protection Best Practices: A Regional Study, Brenda L. Boyd

Dissertations

Problem. A growing concern exists that patients are receiving an increase in radiation exposure while undergoing medical imaging exams. According to a March 2009 report by the National Council on Radiation Protection and Measurements (NCRP), the U.S. population's total exposure to ionizing radiation has nearly doubled over the past two decades. With the introduction of new digital radiology equipment, patient dose is on the rise. Possible reasons for a radiologic technologist's behavior include: influence by availability or lack of equipment, policies, social pressure, attitudes, and a safety culture. Little research has been done in this area, specifically with applying a …

Targeted Therapies In The Treatment Of Advanced Hepatocellular Carcinoma., Zhengyu Wei, Cataldo Doria, Yuan Liu

Department of Surgery Faculty Papers

Hepatocellular carcinoma (HCC) is the most common liver cancer and the third leading cause of cancer death. It has been a major worldwide health problem with more new cases being diagnosed each year. The current available therapies for patients with advanced HCC are extremely limited. Therefore, it is of great clinical interests to develop more effective therapies for systemic treatment of advanced HCC. Several promising target-based drugs have been tested in a number of clinical trials. One breakthrough of these efforts is the approved clinical use of sorafenib in patients with advanced HCC. Targeted therapies are becoming an attractive option …

Intronic Non-Cg Dna Hydroxymethylation And Alternative Mrna Splicing In Honey Bees, Pablo Cingolani, Xiaoyi Cao, Radhika S. Khetani, Chieh-Chun Chen, Melissa Coon, Alya'a Sammak, Aliccia Bollig-Fischer, Susan Land, Yun Huang, Matthew E. Hudson, Mark D. Garfinkel, Sheng Zhong, Gene E. Robinson, Douglas M. Ruden

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Previous whole-genome shotgun bisulfite sequencing experiments showed that DNA cytosine methylation in the honey bee (Apis mellifera) is almost exclusively at CG dinucleotides in exons. However, the most commonly used method, bisulfite sequencing, cannot distinguish 5-methylcytosine from 5-hydroxymethylcytosine, an oxidized form of 5-methylcytosine that is catalyzed by the TET family of dioxygenases. Furthermore, some analysis software programs under-represent non-CG DNA methylation and hydryoxymethylation for a variety of reasons. Therefore, we used an unbiased analysis of bisulfite sequencing data combined with molecular and bioinformatics approaches to distinguish 5-methylcytosine from 5-hydroxymethylcytosine. By doing this, we have performed the first whole …

Review Of Kidney Disease Among Indigenous People, Sasha A. Stumpers, Neil J. Thomson

Research outputs 2013

Kidney disease is a significant health problem for all Australians, but severe kidney disease is more common among Indigenous people than among non- Indigenous people. In particular, the prevalence of chronic kidney disease (CKD) and the overall levels of end-stage kidney disease (ESKD) among Aboriginal and Torres Strait Islander peoples are consistently reported as significantly higher than among other Australians. Information on CKD among Indigenous Australians is available from self-reported survey data, as well as from community-based studies and screening programs [10-20] but the main focus in the literature has been on ESKD. The incidence of ESKD is especially high …

Mers-Cov - Are We On The Verge Of A Pandemic?, Bushra Jamil, Kiren Habib

Department of Medicine

No abstract provided.

The Translational Machinery As A Target For Radiosensitization, Thomas John Hayman

USF Tampa Graduate Theses and Dissertations

Current approaches aimed at improving the efficacy of radiation as a cancer treatment modality involve the development and application of molecularly targeted radiosensitizers, a strategy that requires a thorough understanding of the fundamental processes comprising the cellular radioresponse. Recent data indicating that radiation modifies gene expression primarily through translational control rather than transcriptional events suggests that mRNA translation contributes to cell survival after irradiation. The overall goal of this project is to determine whether the regulatory/rate-limiting components of the translational machinery provide targets for tumor cell radiosensitization. The majority of translation in mammalian cells occurs in a cap-dependent manner and …

Gut Modulator Effects Of Conyza Bonariensis Explain Its Traditional Use In Constipation And Diarrhea, I A. Bukhari, A J. Shah, R A. Khan, S A. Meo, A Khan, A H. Gilani

Department of Biological & Biomedical Sciences

BACKGROUND AND OBJECTIVES:

The current investigation was carried out to explore the pharmacological basis of the crude extract of Conyza bonariensis (Cb.Cr) for its use in constipation and diarrhea.

MATERIALS AND METHODS:

The plant extract of Conyza bonariensis (C. bonariensis) was prepared, isolated guinea-pig ileum and rabbit jejunum preparations were used to evaluate its gut modulator effects.

RESULTS:

The Cb.Cr (0.3-10 mg/mL) exhibited spasmogenic effect in isolated guinea-pig ileum preparation, which was about 19-84% of the acetylcholine maximum. Pretreatment of the tissues with atropine (0.1 µM) abolished the contractile effect, similar to acetylcholine. Among the fractions, only the butanol fraction …

Inhibitory Effect Of Matrine On Blood-Brain Barrier Disruption For The Treatment Of Experimental Autoimmune Encephalomyelitis., Su Zhang, Quan-Cheng Kan, Yuming Xu, Guang-Xian Zhang, Lin Zhu

Department of Neurology Faculty Papers

Dysfunction of the blood-brain barrier (BBB) is a primary characteristic of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been recently found to suppress clinical EAE and CNS inflammation. However, whether this effect of MAT is through protecting the integrity and function of the BBB is not known. In the present study, we show that MAT treatment had a therapeutic effect comparable to dexamethasone (DEX) in EAE rats, with reduced Evans Blue extravasation, increased expression of collagen IV, the major component of the basement …

Is Bisphenol-A Exposure During Pregnancy Associated With Blood Glucose Levels Or Diagnosis Of Gestational Diabetes?, Candace A. Robledo, Jennifer D. Peck, Julie A. Stoner, Hélène Carabin, Linda Cowan, Holger M. Koch, Jean R. Goodman

School of Medicine Publications

Recent epidemiological studies indicate bisphenol A (BPA), an estrogenic chemical used in production of epoxy, polycarbonate, and plastic may increase risk of insulin resistance and type 2 diabetes. Exposure to BPA during pregnancy may contribute to development of gestational diabetes mellitus (GDM), a precursor to type 2 diabetes in women. This pilot study examined the association between BPA exposure, fasting blood glucose levels (FBG), and GDM diagnosis during pregnancy. Banked urine samples from 22 cases of GDM and 72 controls were analyzed for total (free BPA + conjugates) urinary BPA concentrations (μg/L). FBG levels (mg/dl) were obtained from 1-h 50-g …

Management Options For Patients With Chronic Back Pain Without An Etiology, Lenny D. Salzberg, Eron G. Manusov

School of Medicine Publications

The treatment and management of low back pain is complex when there is no specific etiology such as cancer, fracture, or herniated disc. An organized approach to management that follows evidence based guidelines will facilitate care in a problem that reflects a lifetime prevalence of over 70 percent. The purpose of this review is to present a guideline to care for a common disabling process with a very heterogeneous etiology.

Tumor Necrosis Factor-Α And Lymphotoxin-Α Mediate Myocardial Ischemic Injury Via Tnf Receptor 1, But Are Cardioprotective When Activating Tnf Receptor 2., Yanqing Zhang, Jianli Zhao, Wayne Bond Lau, Li-Yuan Jiao, Baojiang Liu, Yuexing Yuan, Xiaoliang Wang, Erhe Gao, Walter J Koch, Xin-Liang Ma, Yajing Wang

Department of Emergency Medicine Faculty Papers

OBJECTIVE: This study determines the roles of tumor necrosis factor-α (TNFα) and lymphotoxin-α (LTα) in post-myocardial infarction (post-MI) cardiac injury, and identifies the TNF receptor type responsible for TNFα- and LTα-mediated cardiac injury.

METHODS AND RESULTS: Adult male wild type (WT), TNFα(-/-), LTα(-/-), TNFR1(-/-), and TNFR2(-/-) mice were subjected to MI via coronary artery occlusion. Functional, histological, and biochemical analyses were performed 1 to 7 days post-MI. In WT mice, MI significantly increased both TNFα and LTα levels in plasma, but in distinct temporal manner. Plasma TNFα peaked 1 day after MI, and decreased toward baseline 3 days after MI. …

Ginsenoside Rd Attenuates Myocardial Ischemia/Reperfusion Injury Via Akt/Gsk-3Β Signaling And Inhibition Of The Mitochondria-Dependent Apoptotic Pathway., Yang Wang, Xu Li, Xiaoliang Wang, Wayne Bond Lau, Yajing Wang, Yuan Xing, Xing Zhang, Xinliang Ma, Feng Gao

Department of Emergency Medicine Faculty Papers

Evidence suggests Ginsenoside Rd (GSRd), a biologically active extract from the medical plant Panax Ginseng, exerts antioxidant effect, decreasing reactive oxygen species (ROS) formation. Current study determined the effect of GSRd on myocardial ischemia/reperfusion (MI/R) injury (a pathological condition where ROS production is significantly increased) and investigated the underlying mechanisms. The current study utilized an in vivo rat model of MI/R injury and an in vitro neonatal rat cardiomyocyte (NRC) model of simulated ischemia/reperfusion (SI/R) injury. Infarct size was measured by Evans blue/TTC double staining. NRC injury was determined by MTT and lactate dehydrogenase (LDH) leakage assay. ROS accumulation and …

Melatonin Supplementation Improves Glycemic Control While Lowering Oxidative Stress In Type 2 Diabetes, Carmine R. Grieco, Sheri R. Colberg, C. Thomas Somma, Andrew G. Thompson, Aaron I. Vinik

Human Movement Studies & Special Education Faculty Publications

The purpose of this investigation was to evaluate the effect of melatonin on glycemic control and oxidative stress (OS) in adults with type 2 diabetes (T2D). Fourteen subjects with T2D (10 female, 4 male; 52.5 ± 5.0 years) were randomly assigned to melatonin (MEL) or placebo groups (PLA) for 42 days, in a crossover design. Subjects ingested 10 mg of MEL or an identical placebo (PLA) 30 minutes prior to sleep. Fasting blood draws occurred at baseline, 42 days, and 84 days. Plasma malondialdehyde, a marker of OS, significantly decreased on MEL (-6.25±2.10 nmol/ml) compared to PLA (0.72±3.30, p=0.028). The …

Xiaoqinglong Granules As Add-On Therapy For Asthma: Latent Class Analysis Of Symptom Predictors Of Response., Qinglin Zha, Seqi Lin, Chi Zhang, Christopher Chang, Hanrong Xue, Cheng Lu, Miao Jiang, Yan Liu, Zuke Xiao, Weiyou Liu, Yunfei Shang, Jianjian Chen, Minyong Wen, Aiping Lu

Department of Medicine Faculty Papers

Xiaoqinglong granules (XQLG) has been shown to be an effective therapy in asthma animal models. We reviewed the literature and conducted this study to assess the impact of XQLG as an add-on therapy to treatment with fluticasone/salmeterol (seretide) in adult patients with mild-to-moderate, persistent asthma. A total of 178 patients were randomly assigned to receive XQLG and seretide or seretide plus placebo for 90 days. Asthma control was assessed by asthma control test (ACT), symptoms scores, FEV(1), and PEF. Baseline patient-reported Chinese medicine (CM)-specific symptoms were analyzed to determine whether the symptoms may be possible indicators of treatment response by …

Some Thoughts About The Historic Events That Led To The First Clinical Implantation Of A Total Artificial Heart, Denton A Cooley

The Texas Heart Institute Journal

No abstract provided.

Preventing Deep Wound Infection After Coronary Artery Bypass Grafting: A Review, Charles S Bryan, William M Yarbrough

The Texas Heart Institute Journal

The consequences of deep wound infections before, during, and after coronary artery bypass grafting have prompted research to clarify risk factors and explore preventive measures to keep infection rates at an irreducible minimum. An analysis of 42 studies in which investigators used multivariate logistic regression analysis revealed that diabetes mellitus and obesity are by far the chief preoperative risk factors. A 4-point preoperative scoring system based on a patient's body mass index and the presence or absence of diabetes is one practical way to determine the risk of mediastinitis, and other risk-estimate methods are being refined. Intraoperative risk factors include …

Low Serum Triglyceride Levels As Predictors Of Cardiac Death In Heart Failure Patients, Guliz Kozdag, Gokhan Ertas, Ender Emre, Yasar Akay, Umut Celikyurt, Tayfun Sahin, Gozde Gorur, Kurtulus Karauzum, Irem Yilmaz, Dilek Ural, Mira Sarsekeyeva

The Texas Heart Institute Journal

Understanding the influence of sex differences on predictors of cardiac mortality rates in chronic heart failure might enable us to lengthen lifetimes and to improve lives. This study describes the influence of sex on cardiovascular mortality rates among chronic heart failure patients.

From January 2003 through December 2009, we evaluated 637 consecutive patients (409 men and 228 women) with chronic heart failure, who ranged in age from 18 through 94 years (mean age, 64 ± 13 yr) and ranged in New York Heart Association (NYHA) functional class from II through IV. The mean follow-up period was 38 ± 15 months, …

Cis And Trans Regulatory Mechanisms Control Ap2-Mediated B Cell Receptor Endocytosis Via Select Tyrosine-Based Motifs., Kathleen Busman-Sahay, Lisa Drake, Anand Sitaram, Michael Marks, James R Drake

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Following antigen recognition, B cell receptor (BCR)-mediated endocytosis is the first step of antigen processing and presentation to CD4+ T cells, a crucial component of the initiation and control of the humoral immune response. Despite this, the molecular mechanism of BCR internalization is poorly understood. Recently, studies of activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) have shown that mutations within the BCR subunit CD79b leads to increased BCR surface expression, suggesting that CD79b may control BCR internalization. Adaptor protein 2 (AP2) is the major mediator of receptor endocytosis via clathrin-coated pits. The BCR contains five putative AP2-binding …

Inhibitory Effect Of Il-17 On Neural Stem Cell Proliferation And Neural Cell Differentiation., Zichen Li, Ke Li, Lin Zhu, Quancheng Kan, Yaping Yan, Priyanka Kumar, Hui Xu, Abdolmohamad Rostami, Guang-Xian Zhang

Department of Neurology Faculty Papers

BACKGROUND: IL-17, a Th17 cell-derived proinflammatory molecule, has been found to play an important role in the pathogenesis of autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). While IL-17 receptor (IL-17R) is expressed in many immune-related cells, microglia, and astrocytes, it is not known whether IL-17 exerts a direct effect on neural stem cells (NSCs) and oligodendrocytes, thus inducing inflammatory demyelination in the central nervous system.

METHODS: We first detected IL-17 receptor expression in NSCs with immunostaining and real time PCR. We then cultured NSCs with IL-17 and determined NSC proliferation by neurosphere formation …