DOCSLIB.ORG

Additively with Eotaxin Factor for Eosinophils and Functions Cutting

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Additively with Eotaxin Factor for Eosinophils and Functions Cutting Cutting Edge: Serotonin Is a Chemotactic Factor for Eosinophils and Functions Additively with Eotaxin This information is current as Stefen A. Boehme, Francisco M. Lio, Lyudmila Sikora, of September 26, 2021. Terlika S. Pandit, Karine Lavrador, Savita P. Rao and P. Sriramarao J Immunol 2004; 173:3599-3603; ; doi: 10.4049/jimmunol.173.6.3599 http://www.jimmunol.org/content/173/6/3599 Downloaded from References This article cites 21 articles, 5 of which you can access for free at: http://www.jimmunol.org/content/173/6/3599.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 26, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2004 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. THE JOURNAL OF IMMUNOLOGY CUTTING EDGE Cutting Edge: Serotonin Is a Chemotactic Factor for Eosinophils and Functions Additively with Eotaxin1 Stefen A. Boehme,*† Francisco M. Lio,† Lyudmila Sikora,* Terlika S. Pandit,* Karine Lavrador,† Savita P. Rao,* and P. Sriramarao2* Elevated levels of serotonin (5-hydroxytryptamine, 5-HT) demonstrate the importance of the eotaxin-CCR3 interaction are observed in the serum of asthmatics. Herein, we dem- in allergic asthma, but they also suggest that other eosinophil onstrate that 5-HT functions independently as an eosino- chemoattractants that function through different receptors are phil chemoattractant that acts additively with eotaxin. likely to be involved in selectively attracting eosinophils to re- 5-HT2A receptor antagonists (including MDL-100907 spiratory tissue. and cyproheptadine (CYP)) were found to inhibit 5-HT- 5-Hydroxytryptamine (5-HT, serotonin) is one of the most Downloaded from induced, but not eotaxin-induced migration. Intravital extensively studied neurotransmitters of the CNS that is also microscopy studies revealed that eosinophils roll in re- present in constituents of the immune system. It is an impor- tant inflammatory mediator that is released by mast cells upon sponse to 5-HT in venules under conditions of physio- IgE cross-linking and has recently been shown to play a role in logical shear stress, which could be blocked by pretreating the pathophysiology of asthma (8). Increased levels of free eosinophils with CYP. OVA-induced pulmonary eosino- 5-HT are present in the plasma of symptomatic asthmatic pa- http://www.jimmunol.org/ philia in wild-type mice was significantly inhibited using tients compared with asymptomatic subjects (9), and recent CYP alone and maximally in combination with a CCR3 studies have also demonstrated that 5-HT can induce lung fi- receptor antagonist. Interestingly, OVA-induced pulmo- broblasts to produce eotaxin (10). Although these studies sug- ؊/؊ nary eosinophilia in eotaxin-knockout (Eot ) mice was gest a role for 5-HT in allergic asthma, a direct effect of 5-HT in inhibited by treatment with the 5-HT2A but not CCR3 mediating eosinophil recruitment/chemotaxis relative to the receptor antagonist. These results suggest that 5-HT is a function of eotaxin has not been determined. In the present potent eosinophil-active chemoattractant that can func- study, we have investigated the role of 5-HT to function di- tion additively with eotaxin and a dual CCR3/5-HT2A rectly as an eosinophil-specific chemoattractant. by guest on September 26, 2021 receptor antagonist may be more effective in blocking al- lergen-induced eosinophil recruitment. The Journal of Materials and Methods Immunology, 2004, 173: 3599–3603. Eosinophil isolation Eosinophils were purified from the peripheral blood of allergic donors (11). For the in vivo experiments, eosinophils were fluorescently labeled with carboxy- osinophils play a prominent proinflammatory role in fluorescein diacetate (CFDA, Invitrogen, Carlsbad, CA) (12). airway allergic inflammation including the pathogene- Synthesis of the CCR3 antagonist N-{1(S)-[4-(3,4- E sis of asthma (1, 2, 3). This inflammatory role is medi- dichlorobenzyl)piperazin-1-yl-methyl]-2-methylpropyl}-4- ated by lipid mediators, cytokines, and toxic granule proteins methylbenzamide dihydrochloride salt (DPM) released by activated eosinophils (4). Several studies have dem- DPM was synthesized following the protocol described in patent EP 0 903 349 onstrated a critical role for eotaxin in the selective recruitment A2. This antagonist has a Ki value of 62 nM for the human CCR3 receptor and of eosinophils following allergen challenge (5–7). In experi- Ͼ10 ␮M for the 5-HT2 receptors (data not shown). mental studies of allergic asthma, treatment of allergen-chal- Chemotaxis assays lenged mice with an anti-eotaxin Ab resulted in a 56% inhibi- Boyden chamber assay. The ability of 5-HT to induce eosinophil migra- Ϫ Ϫ tion of pulmonary eosinophil influx (7). Eot / mice tion was tested using the Boyden chamber assay (11). In some experiments, demonstrated a 70% reduction of eosinophils in bronchoalveo- eosinophils were preincubated with cyproheptadine (CYP), ketanserin, pirenperone, or DPM for 15 min before the chemotaxis assay. lar lavage (BAL)3 fluid 18 h postallergen challenge (5), while Ϫ/Ϫ ϳ Transwell chamber assay. Eosinophils isolated from different allergic do- eotaxin receptor CCR3 mice exhibited an 60% decrease nors (n ϭ 4) were preincubated with MDL-100907 (13, 14) (kindly pro- in pulmonary eosinophilia postchallenge (6). These studies vided by Dr. H. Y. Huang, Columbia University, New York, NY) at a *La Jolla Institute for Molecular Medicine, San Diego, CA 92121; and †Neurocrine Bio- 2 Address correspondence and reprint requests to Dr. P. Sriramarao, Division of Vascular sciences, Inc., San Diego, CA 92121 Biology, La Jolla Institute for Molecular Medicine, 4570 Executive Drive, San Diego, CA 92121. E-mail address: [email protected] Received for publication May 12, 2004. Accepted for publication July 19, 2004. 3 Abbreviations used in this paper: BAL, bronchoalveolar lavage; %-HT, 5-hydroxytryp- The costs of publication of this article were defrayed in part by the payment of page charges. tamine (serotonin); CFDA, carboxyfluorescein diacetate; DPM, N-{1(S)-[4-(3,4-dichlo- This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. robenzyl)piperazin-1-yl-methyl]-2-methylpropyl}-4-methyl benzamide dihydrochloride Section 1734 solely to indicate this fact. salt; CYP, cyproheptadine; IVM, intravital microscopy; RF, rolling fraction; WT, wild 1 This work was supported by National Institutes of Health Grant AI 35796 and California type; hpf, high-power field. Tobacco-Related Disease Research Program Grant 10 RT-0171 (to P.S.). Copyright © 2004 by The American Association of Immunologists, Inc. 0022-1767/04/$02.00 3600 CUTTING EDGE: SEROTONIN: A CHEMOTACTIC FACTOR FOR EOSINOPHILS concentration of 20 ␮M for 20 min or with medium alone before addition Hospital Medical Center, Cincinnati, OH) (5, 15). In brief, mice were sensi- (2 ϫ 105/well) to Matrigel-coated (200 ␮g/ml) Transwell chambers. Cul- tized by two i.p. injections of 50 ␮g OVA in 200 ␮l of alum (Pierce). Nonsen- ture medium alone or medium containing 5-HT (100 nM) or eotaxin (50 sitized mice received 200 ␮l of alum alone. Ten days after the second injection, nM) was added to the lower chamber. In certain experiments, 5-HT was CYP (0.2 mg/mouse), DPM (2 mg/mouse), or both were administered (i.p.) to added to only upper or both upper and lower chambers and incubated at different groups of mice (n ϭ 3 mice/group). Fifteen minutes after injection of 37°C for 4 h, after which the chambers were removed and the number of the inhibitor, mice were exposed to three inhalations (30 min each) of aerosol- migrated cells was quantitated and expressed as a percentage of total cells ized OVA (10 mg/ml in 0.9% sterile saline) at 1-h intervals. Nonsensitized mice added to the well. received an i.p. injection of vehicle and aerosol challenge of saline only. One hour after the last aero-allergen challenge, mice were sacrificed and processed RT-PCR for BAL fluid collection to determine eosinophil counts (15). Amplification of the gene for 5-HT2A was performed by RT-PCR of eosino- phil RNA isolated from human allergic subjects. Eosinophil reverse transcrip- tase product underwent two rounds of PCR amplification using the following Results conditions: 15 s at 94°C,30sat57°C, and 45 s at 72°C for 30 cycles. The Eosinophils respond functionally to 5-HT sequence of the primers was as follows: 5-HT2A receptor external sense primer, Ј Ј Ј 5-HT alone was found to induce migration of human eosino- 5 -CTATAGGTCAGCCTTTTCACG-3 and external antisense primer, 5 - Ϫ6 GCCTTCCACAGTTGCCACG-3Ј. Two microliters of the first PCR was phils in a dose-dependent manner, which was maximal at 10 used as a template for the second round. The internal nested primer sequences M (Fig. 1A). Furthermore, 5-HT, at various concentrations, were as follows: 5-HT2A receptor internal nested sense primer, 5Ј-TATAT had an additive effect on eosinophil chemotaxis when tested in Ј Ј TCAGTGTCAGTACAAGG-3 and internal nested antisense primer, 5 - combination with 50 nM eotaxin. As a positive control, 50 nM CCTATCACACACAGCTACC-3Ј. All primer pairs spanned an intron. eotaxin alone also induced eosinophil migration, consistent Downloaded from Western blot analysis with our previous studies (11). The migration induced by Western blot analysis was conducted using an anti-5-HT2A receptor Ab (BD 5-HT was chemotactic and not chemokinetic (Fig.
Load more

Recommended publications
  • Histamine Receptors
    Tocris Scientific Review Series Tocri-lu-2945 Histamine Receptors Iwan de Esch and Rob Leurs Introduction Leiden/Amsterdam Center for Drug Research (LACDR), Division Histamine is one of the aminergic neurotransmitters and plays of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit an important role in the regulation of several (patho)physiological Amsterdam, De Boelelaan 1083, 1081 HV, Amsterdam, The processes. In the mammalian brain histamine is synthesised in Netherlands restricted populations of neurons that are located in the tuberomammillary nucleus of the posterior hypothalamus.1 Dr. Iwan de Esch is an assistant professor and Prof. Rob Leurs is These neurons project diffusely to most cerebral areas and have full professor and head of the Division of Medicinal Chemistry of been implicated in several brain functions (e.g. sleep/ the Leiden/Amsterdam Center of Drug Research (LACDR), VU wakefulness, hormonal secretion, cardiovascular control, University Amsterdam, The Netherlands. Since the seventies, thermoregulation, food intake, and memory formation).2 In histamine receptor research has been one of the traditional peripheral tissues, histamine is stored in mast cells, eosinophils, themes of the division. Molecular understanding of ligand- basophils, enterochromaffin cells and probably also in some receptor interaction is obtained by combining pharmacology specific neurons. Mast cell histamine plays an important role in (signal transduction, proliferation), molecular biology, receptor the pathogenesis of various allergic conditions. After mast cell modelling and the synthesis and identification of new ligands. degranulation, release of histamine leads to various well-known symptoms of allergic conditions in the skin and the airway system. In 1937, Bovet and Staub discovered compounds that antagonise the effect of histamine on these allergic reactions.3 Ever since, there has been intense research devoted towards finding novel ligands with (anti-) histaminergic activity.
    [Show full text]
  • Receptor Antagonist (H RA) Shortages | May 25, 2020 2 2 2 GERD4,5 • Take This Opportunity to Determine If Continued Treatment Is Necessary
    H2-receptor antagonist (H2RA) Shortages Background . 2 H2RA Alternatives . 2 Therapeutic Alternatives . 2 Adults . 2 GERD . 3 PUD . 3 Pediatrics . 3 GERD . 3 PUD . 4 Tables Table 1: Health Canada–Approved Indications of H2RAs . 2 Table 2: Oral Adult Doses of H2RAs and PPIs for GERD . 4 Table 3: Oral Adult Doses of H2RAs and PPIs for PUD . 5 Table 4: Oral Pediatric Doses of H2RAs and PPIs for GERD . 6 Table 5: Oral Pediatric Doses of H2RAs and PPIs for PUD . 7 References . 8 H2-receptor antagonist (H2RA) Shortages | May 25, 2020 1 H2-receptor antagonist (H2RA) Shortages BACKGROUND Health Canada recalls1 and manufacturer supply disruptions may be causing shortages of commonly used acid-reducing medications called histamine H2-receptor antagonists (H2RAs) . H2RAs include cimetidine, famotidine, nizatidine and ranitidine . 2 There are several Health Canada–approved indications of H2RAs (see Table 1); this document addresses the most common: gastroesophageal reflux disease (GERD) and peptic ulcer disease (PUD) . 2 TABLE 1: HEALTH CANADA–APPROVED INDICATIONS OF H2RAs H -Receptor Antagonists (H RAs) Health Canada–Approved Indications 2 2 Cimetidine Famotidine Nizatidine Ranitidine Duodenal ulcer, treatment ü ü ü ü Duodenal ulcer, prophylaxis — ü ü ü Benign gastric ulcer, treatment ü ü ü ü Gastric ulcer, prophylaxis — — — ü GERD, treatment ü ü ü ü GERD, maintenance of remission — ü — — Gastric hypersecretion,* treatment ü ü — ü Self-medication of acid indigestion, treatment and prophylaxis — ü† — ü† Acid aspiration syndrome, prophylaxis — — — ü Hemorrhage from stress ulceration or recurrent bleeding, — — — ü prophylaxis ü = Health Canada–approved indication; GERD = gastroesophageal reflux disease *For example, Zollinger-Ellison syndrome .
    [Show full text]
  • Histamine in the Control of Gastric Acid Secretion: a Topic Review
    Pharmacological Research 47 (2003) 299–304 Histamine in the control of gastric acid secretion: a topic review Elisabetta Barocelli∗, Vigilio Ballabeni Dipartimento di Scienze Farmacologiche, Biologiche e Chimiche Applicate, Università di Parma, Parco Area delle Scienze, 27/A, Parma 43100, Italy Accepted 30 December 2002 Abstract In this paper, the current knowledge about the role of histamine in the control of gastric acid secretion is reviewed. In particular, we focus this topic into three sections considering the recent insights on: histamine receptor subtypes involved in gastric acid secretion, the interplay between neuronal–hormonal–paracrine pathways and the cerebral histaminergic control of gastric secretion. From the careful perusal of scientific literature, the fundamental role of histamine as local stimulator of gastric acid secretion via H2 receptors is fairly confirmed while for the H3 receptor only a minor modulating role is hypothesized. An undisputed function of ECL cells as controllable source of histamine within the so-called gastrin–ECL cell–parietal cell axis is generally proposed and the intriguing possibility of a remote control of gastric secretion via H3 receptors is also suggested. © 2003 Elsevier Science Ltd. All rights reserved. Keywords: Secretagogue; Histaminergic system; Gastric acid secretion 1. Introduction the central and in the peripheral neuronal networks [7] and its cloning [8] major attention was devoted by researchers Although histamine has been found to be a potent secret- mainly to the re-examination of apparently anomalous ef- agogue of acid secretion since 1920 [1], its physiologic role fects exerted by histamine. Also for gastric acid secretion, in the stomach is again a subject of debate as also acetyl- although here histamine plays an undisputed central role choline and gastrin are of prime importance in the stimula- through H2 receptors activation [9], the possible involvement tion of gastric acid production.
    [Show full text]
  • Histamine H2-Receptor Antagonists Improve Non-Steroidal Anti-Inflammatory Drug-Induced Intestinal Dysbiosis
    International Journal of Molecular Sciences Article Histamine H2-Receptor Antagonists Improve Non-Steroidal Anti-Inflammatory Drug-Induced Intestinal Dysbiosis Rei Kawashima, Shun Tamaki, Fumitaka Kawakami, Tatsunori Maekawa and Takafumi Ichikawa * Department of Regulation Biochemistry, Kitasato University Graduate School of Medical Sciences, Kanagawa 252-0374, Japan; [email protected] (R.K.); [email protected] (S.T.); [email protected] (F.K.); [email protected] (T.M.) * Correspondence: [email protected]; Tel.: +81-42-778-8863 Received: 8 October 2020; Accepted: 30 October 2020; Published: 31 October 2020 Abstract: Dysbiosis, an imbalance of intestinal flora, can cause serious conditions such as obesity, cancer, and psychoneurological disorders. One cause of dysbiosis is inflammation. Ulcerative enteritis is a side effect of non-steroidal anti-inflammatory drugs (NSAIDs). To counteract this side effect, we proposed the concurrent use of histamine H2 receptor antagonists (H2RA), and we examined the effect on the intestinal flora. We generated a murine model of NSAID-induced intestinal mucosal injury, and we administered oral H2RA to the mice. We collected stool samples, compared the composition of intestinal flora using terminal restriction fragment length polymorphism, and performed organic acid analysis using high-performance liquid chromatography. The intestinal flora analysis revealed that NSAID [indomethacin (IDM)] administration increased Erysipelotrichaceae and decreased Clostridiales but that both had improved with the concurrent administration of H2RA. Fecal levels of acetic, propionic, and n-butyric acids increased with IDM administration and decreased with the concurrent administration of H2RA. Although in NSAID-induced gastroenteritis the proportion of intestinal microorganisms changes, leading to the deterioration of the intestinal environment, concurrent administration of H2RA can normalize the intestinal flora.
    [Show full text]
  • Sensory Neuron Regulation of Gastrointestinal Inflammation And
    Key Symposium doi: 10.1111/joim.12591 Sensory neuron regulation of gastrointestinal inflammation and bacterial host defence N. Y. Lai, K. Mills & I. M. Chiu From the Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA Content List – Read more articles from the symposium: 13th Key Symposium - Bioelectronic Medicine: Technology targeting molecular mechanisms. Abstract. Lai NY, Mills K, Chiu IM (Harvard Medical recent work on the mechanisms of bacterial detec- School, Boston, MA, USA). Sensory neuron tion by distinct subtypes of gut-innervating sen- regulation of gastrointestinal inflammation and sory neurons. Upon activation, sensory neurons bacterial host defence (Key Symposium). J Intern communicate to the immune system to modulate Med 2017; 282:5–23. tissue inflammation through antidromic signalling and efferent neural circuits. We discuss how this Sensory neurons in the gastrointestinal tract have neuro-immune regulation is orchestrated through multifaceted roles in maintaining homeostasis, transient receptor potential ion channels and sen- detecting danger and initiating protective sory neuropeptides including substance P, calci- responses. The gastrointestinal tract is innervated tonin gene-related peptide, vasoactive intestinal by three types of sensory neurons: dorsal root peptide and pituitary adenylate cyclase-activating ganglia, nodose/jugular ganglia and intrinsic pri- polypeptide. Recent studies also highlight a role for mary afferent neurons. Here, we examine how sensory
    [Show full text]
  • International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors
    1521-0081/67/3/601–655$25.00 http://dx.doi.org/10.1124/pr.114.010249 PHARMACOLOGICAL REVIEWS Pharmacol Rev 67:601–655, July 2015 Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics ASSOCIATE EDITOR: ELIOT H. OHLSTEIN International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors Pertti Panula, Paul L. Chazot, Marlon Cowart, Ralf Gutzmer, Rob Leurs, Wai L. S. Liu, Holger Stark, Robin L. Thurmond, and Helmut L. Haas Department of Anatomy, and Neuroscience Center, University of Helsinki, Finland (P.P.); School of Biological and Biomedical Sciences, University of Durham, United Kingdom (P.L.C.); AbbVie, Inc. North Chicago, Illinois (M.C.); Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany (R.G.); Department of Medicinal Chemistry, Amsterdam Institute of Molecules, Medicines and Systems, VU University Amsterdam, The Netherlands (R.L.); Ziarco Pharma Limited, Canterbury, United Kingdom (W.L.S.L.); Institute of Pharmaceutical and Medical Chemistry (H.S.) and Institute of Neurophysiology, Medical Faculty (H.L.H.), Heinrich-Heine-University Duesseldorf, Germany; and Janssen Research & Development, LLC, San Diego, California (R.L.T.) Abstract ....................................................................................602 Downloaded from I. Introduction and Historical Perspective .....................................................602 II. Histamine H1 Receptor . ..................................................................604 A. Receptor Structure
    [Show full text]
  • Studies on Serotonin (5-HT) 3-Receptor Antagonist Effects Of
    Jpn. J. Pharmacol. 67, 185-194 (1995) Studies on Serotonin (5-HT)3-Receptor Antagonist Effects of Enantiomers of 4, 5,6,7-Tetrahydro-1H-Benzimidazole Derivatives Takeshi Kamato, Hiroyuki Ito, Takeshi Suzuki, Keiji Miyata and Kazuo Honda Neuroscience and Gastrointestinal Research Laboratory, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305, Japan Received June 24, 1994 Accepted November 28, 1994 ABSTRACT-We assessed the 5-HT3-receptor antagonist effects of 4,5,6,7-1H-benzimidazole compounds which are derivatives of YM060, a potent and selective 5-HT3-receptor antagonist, in isolated guinea pig co- lon. YM114 (KAE-393), YM-26103-2, YM-26308-2 (3 x 10-9 to 3 x 10-8 M) produced concentration-depend- ent shifts to the right of the dose-response curves for both 5-HT and 2-methyl-5-HT (2-Me-5-HT). YM114 (pA2=9.08 against 5-HT, pA2=8.88 against 2-Me-5-HT), YM-26103-2 (pA2=8.27 against 5-HT, pA2 = 8.19 against 2-Me-5-HT), and YM-26308-2 (pA2 = 8.58 against 5-HT, pA2 = 8.4 against 2-Me-5-HT) show- ed similar pA2 values irrespective of the agonist used, suggesting that they have 5-HT3-receptor blocking activity irrespective of the N-position at the aromatic ring. Since these compounds have an asymmetric center, their enantiomers exist. The S-isomers were one to three orders of magnitude less potent than the respective R-isomer compounds, indicating that the stereochemical configuration of 4,5,6,7-tetrahydro-lH- benzimidazoles is an important determinant of their affinity for 5-HT3 receptors.
    [Show full text]
  • Kenneth Martin Rosenberg Email: [email protected], [email protected] 660 West Redwood Street, Howard Hall Room 332D, Baltimore, MD, 21201
    The impact of the non-immune chemiome on T cell activation Item Type dissertation Authors Rosenberg, Kenneth Publication Date 2020 Abstract T cells are critical organizers of the immune response and rigid control over their activation is necessary for balancing host defense and immunopathology. It takes 3 signals provided by dendritic cells (DC) to fully activate a T cell response – T ce... Keywords signaling; T cell; T-Lymphocytes--immunology Download date 02/10/2021 13:41:58 Link to Item http://hdl.handle.net/10713/14477 Kenneth Martin Rosenberg Email: [email protected], [email protected] 660 West Redwood Street, Howard Hall Room 332D, Baltimore, MD, 21201 EDUCATION MD, University of Maryland, Baltimore, MD Expected May 2022 PhD, University of Maryland, Baltimore, MD December 2020 Graduate Program: Molecular Microbiology and Immunology (MMI) BS, University of Maryland, College Park, MD May 2013 Major: Bioengineering, cum laude University Honors Citation, Gemstone Citation RESEARCH EXPERIENCE UMSOM Microbiology and Immunology Baltimore, MD July 2016-present PhD Candidate Principal Investigator: Dr. Nevil Singh Thesis: The impact of the non-immune chemiome on T cell activation Examined environmental stimuli from classically “non-immune” sources – growth factors, hormones, neurotransmitters, etc. – act to modulate T cell signaling pathways and the functional effects of activating encounters with dendritic cells. UMSOM Anatomy and Neurobiology Baltimore, MD May-August 2015 Rotating student Principal Investigator: Dr. Asaf Keller Studied the role of descending modulation pathways on affective pain transmission. Performed tract- tracing experiments using targeted injection of Cholera toxin subunit B into the lateral parabrachial nucleus and ventrolateral periaqueductal gray of anesthetized transgenic mice.
    [Show full text]
  • The Structure and Function of V1b Vasopressin Receptor
    The Structure and Function of V1b Vasopressin Receptors Yukie Goto A thesis submitted to the University of Birmingham for the degree of Doctor of Philosophy School of Biosciences University of Birmingham Edgbaston, Birmingham B15 2TT, United Kingdom September 2009 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. Acknowledgement Firstly I would like to thank my supervisor Professor Mark Wheatley for giving me this opportunity to participate in his research, and for his support and guidance throughout my study. I would also like to thank those who have worked in his research group: in particular John for providing us with molecular models of vasopressin receptors; Alex, Mattew, Denise, Cymone and Amelia, for equipping me with the laboratory techniques required for carrying out this study; and Rachel and Richard for their companies and supports in the research group for last few years. I am truly grateful to Dr. David Poyner and Prof. Ian Martin for their inspiring teachings on this subject area in my undergraduate years. My gratitude goes to Rosemary for her conscientious hard work in looking after laboratories, equipments, and students; and to Eva, David, Karthik, Prof.
    [Show full text]
  • Histamine H2-Antagonists, Proton Pump Inhibitors and Other Drugs That Alter Gastric Acidity
    Jack DeRuiter, Principles of Drug Action 2, Fall 2001 HISTAMINE H2-ANTAGONISTS, PROTON PUMP INHIBITORS AND OTHER DRUGS THAT ALTER GASTRIC ACIDITY I. Introduction Peptide ulcer disease (PUD) is a group of upper gastrointestinal tract disorders that result from the erosive action of acid and pepsin. Duodenal ulcer (DU) and gastric ulcer (GU) are the most common forms although PUD may occur in the esophagus or small intestine. Factors that are involved in the pathogenesis and recurrence of PUD include hypersecretion of acid and pepsin and GI infection by Helicobacter pylori, a gram-negative spiral bacterium. H. Pylori has been found in virtually all patients with DU and approximately 75% of patients with GU. Some risk factors associated with recurrence of PUD include cigarette smoking, chronic use of ulcerogenic drugs (e.g. NSAIDs), male gender, age, alcohol consumption, emotional stress and family history. The goals of PUD therapy are to promote healing, relieve pain and prevent ulcer complications and recurrences. Medications used to heal or reduce ulcer recurrence include antacids, antimuscarinic drugs, histamine H2-receptor antagonists, protective mucosal barriers, proton pump inhibitors, prostaglandins and bismuth salt/antibiotic combinations. A characteristic feature of the stomach is its ability to secrete acid as part of its involvement in digesting food for absorption later in the intestine. The presence of acid and proteolytic pepsin enzymes, whose formation from pepsinogen is facilitated by the low gastric pH, is generally assumed to be required for the hydrolysis of proteins and other foods. The acid secretory unit of the gastric + + mucosa is the parietal (oxyntic) cell.
    [Show full text]
  • Regulatory Roles of Histamine in Pre-Eclampsia
    Placental Genomics: Regulatory Roles of Histamine in Pre-eclampsia Obed Brew A commentary submitted in partial fulfilment of the requirements of University of West London for the degree of Doctor of Philosophy 2017 2 Acknowledgements My sincere thanks to Dr Mark Sullivan and Professor Anthony Woodman for their dedicated and continual support for this work. My sincere thanks also to my family for their patience and endurance. Acts 20:24 3 Abstract Aim: Pre-eclampsia (PE) is a multifactorial pregnancy related disorder and a major cause of perinatal mortality. Mothers who develop PE present with clinical symptoms akin to experimentally induced elevated histamine. Maternal blood histamine is elevated, while Diamine Amine Oxidase (DAO) level is diminished in PE. The abnormalities in placental development and functions linked to aetiology of PE have similarities with effects of elevated histamine in other tissues, yet the effects of the elevated histamine on placental function were not directly investigated. Therefore, a series of studies were undertaken and published to increase our knowledge and elucidate our understanding on: (1) the functionality of elevated histamine in the placenta; (2) the causes of the elevated histamine in PE placentae, and (3) of the effects of the elevated histamine on placental gene expression and the implications for PE. Methods: A series of published high-throughput methodologies have been critically discussed in this commentary. Molecular biotechnology and bioinformatics methodologies such as, ex vivo elevated histamine placental explant model, gene cloning, RT-qPCR, In situ hybridization, microarrays, enzymological analysis, ELISA, Immunohistochemistry, RNA expression array assay analysis, integrated meta-gene analyses, Gene Set Enrichment Analysis, Gene Ontology and biological pathway analyses, Leading Edge Metagene analysis, Systematic Reviews with Meta- analysis and Causal effect analysis have been discussed.
    [Show full text]
  • Efficacy of Serotonin Receptor Agonists in the Treatment of Functional Dyspepsia: a Meta-Analysis
    Systematic review/Meta-analysis Efficacy of serotonin receptor agonists in the treatment of functional dyspepsia: a meta-analysis Man Jin1, Yali Mo1, Kaisheng Ye2, Mingxian Chen3, Yi Liu1, Cao He1 1Department of Medicine, Hangzhou Seventh People’s Hospital, Zhejiang, China Corresponding author: 2Hangzhou Wengjingtang Combination of Chinese Traditional and Western Medicine Kaisheng Ye Clinic, Zhejiang, China Hangzhou Kanghui 3Department of Digestive Diseases, Chinese Traditional Medicine Research Institute Combination of of Zhejiang Province, China Traditional and Western Medicine Clinic Submitted: 23 August 2016 310019 Zhejiang, China Accepted: 1 January 2017 Phone: 15397010817 Fax: 0571-58123951 Arch Med Sci 2019; 15, 1: 23–32 E-mail: DOI: https://doi.org/10.5114/aoms.2017.69234 [email protected] Copyright © 2017 Termedia & Banach Abstract Introduction: Functional dyspepsia (FD) is typically treated with serotonin receptor (5-HT) agonists such as cisapride, mosapride, tegaserod and tan- dospirone citrate. However, there are conflicting efficacy data, possibly due to significant heterogeneity between studies. In this meta-analysis, we an- alyzed the efficacy and safety data from studies evaluating the efficacy of serotonin receptor agonists in patients with FD. Material and methods: Relevant studies were selected from the Medline, Cochrane, EMBASE, and Google Scholar databases. The meta-analysis in- cluded 10 RCTs which evaluated the efficacy of serotonin receptor agonists in patients with FD (final total of 892 patients in the serotonin receptor agonist group, and 640 participants in the placebo group). The primary out- comes were the response rates and abdominal symptoms score. The Co- chrane Collaboration’s tool was used to assess risk. Sensitivity analysis was carried out using the leave-one-out approach.
    [Show full text]