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Giorgos Bamias, Ioanna Delladetsima, Marina Perdiki, Spyros I Siakavellas, Dimitrios Goukos, George V Papatheodoridis, George L Daikos, Helen Gogas
Anti-CTL4-A therapy is associated with development of colitis. We characterized ipilimumab-associated colitis in nine melanoma patients (6 male, mean age: 55.3-yrs). Median value for diarrhea grade was 2, number of ipilimumab doses 2, and interval since last administration 3-wks. Endoscopic characteristics resembled inflammatory bowel disease and histology revealed predominance of plasmacytes or CD4+ T-cells. We observed significant upregulation of Th1 and Th17 effector pathways (>10-fold increase for IFN-γmRNA, >5-fold for IL-17A, p < 0...
August 9, 2017: Cancer Investigation
Roberto A Palomares, David J Hurley, Amelia R Woolums, Jacqueline E Parrish, Kenny V Brock
Immunosuppression caused by bovine viral diarrhea virus (BVDV) has been associated with lymphocyte depletion, leukopenia and impairment of leukocyte function; however, no work has been done on the relationship between BVDV and regulatory T lymphocytes (Tregs). The objective of this study was to compare the mRNA expression of genes associated with Tregs (CD25, FoxP3, CTLA4, and IDO), after experimental infection of beef calves with low (LV) or high (HV) virulence BVDV. Thirty BVDV-naïve calves were randomly assigned to three groups...
December 2014: Comparative Immunology, Microbiology and Infectious Diseases
Pingfang Song, Stephen S Rekow, Corey-Ayne Singleton, Harmanjatinder S Sekhon, Gregory A Dissen, Minerva Zhou, Barbara Campling, Jon Lindstrom, Eliot R Spindel
Synthesis of acetylcholine (ACh) by non-neuronal cells is now well established and plays diverse physiologic roles. In neurons, the Na(+) -dependent, high affinity choline transporter (CHT1) is absolutely required for ACh synthesis. In contrast, some non-neuronal cells synthesize ACh in the absence of CHT1 indicating a fundamental difference in ACh synthesis compared to neurons. The aim of this study was to identify choline transporters, other than CHT1, that play a role in non-neuronal ACh synthesis. ACh synthesis was studied in lung and colon cancer cell lines focusing on the choline transporter-like proteins, a five gene family choline-transporter like protein (CTL)1-5...
August 2013: Journal of Neurochemistry
Simone da Silva Santos, Taane G Clark, Susana Campino, Martha Cecília Suarez-Mutis, Kirk A Rockett, Dominic P Kwiatkowski, Octavio Fernandes
The Brazilian Amazon is a hypo-endemic malaria region with nearly 300,000 cases each year. A variety of genetic polymorphisms, particularly in erythrocyte receptors and immune response related genes, have been described to be associated with susceptibility and resistance to malaria. In order to identify polymorphisms that might be associated with malaria clinical outcomes in a Brazilian Amazonian population, sixty-four human single nucleotide polymorphisms in 37 genes were analyzed using a Sequenom massARRAY iPLEX platform...
2012: PloS One
Denis Rommel, Jorge Abarca-Quinones, Christine De Saeger, Frank Peeters, Isabelle Leclercq, Thierry Duprez
PURPOSE: To investigate which transmembrane choline transporters and intracellular choline kinases play a prominent role at gene expression level in the rise of the total choline (tCho) peak at proton MR spectra in a rodent rhabdomyosarcoma model. MATERIALS AND METHODS: Twenty-two rats bearing grafted bilateral syngenic rhabdomyosarcoma were examined on a clinical 3 T MR system. Total choline concentration was measured from proton MR spectra using cubic centimeter volumes of interest (VOIs) located contiguously along the greater axis of the tumour...
September 2012: Magnetic Resonance Imaging
Gaetano Finocchiaro, Serena Pellegatta
PURPOSE OF REVIEW: During recent years different approaches have been explored to raise effective antitumor responses against brain tumors and particularly glioblastomas (GBMs). In most cases, cancer vaccines were based on autologous dendritic cells loaded with GBM peptides or whole tumor lysates. Many phase I-II studies showed that such strategy is feasible and nontoxic but failed to provide convincing evidence of its efficacy. This was due to study design and other biological issues: local immune suppression and insufficient characterization of appropriate epitopes appear as particularly relevant...
December 2011: Current Opinion in Neurology
B Vogt, M Warncke, B Micheel, A Sheriff
Peripheral T-cell (TC) tolerance can be induced by tolerogenic antigen-presenting cell (APC). A prerequisite is the reduction or blockade of B7 of APC. Besides dendritic cell, B cells can be used as APC. Here, we show the generation B cells with reduced B7 expression by lentiviral transduction of endoplasmic reticulum (ER)-directed CTLA4. Vectors coding for the human CTL4-Ig were used for the human B-cell line Raji. Transduction efficiency was over 90% (MOI = 3). For the murine B-cell line A20 and for primary mouse B cells, murine CTLA4 was used...
May 2009: Autoimmunity
Giovanna Jaramillo-Gutierrez, Janneth Rodrigues, Georges Ndikuyeze, Michael Povelones, Alvaro Molina-Cruz, Carolina Barillas-Mury
BACKGROUND: Functional screens based on dsRNA-mediated gene silencing identified several Anopheles gambiae genes that limit Plasmodium berghei infection. However, some of the genes identified in these screens have no effect on the human malaria parasite Plasmodium falciparum; raising the question of whether different mosquito effector genes mediate anti-parasitic responses to different Plasmodium species. RESULTS: Four new An. gambiae (G3) genes were identified that, when silenced, have a different effect on P...
2009: BMC Microbiology
Anna K D Schnitger, Hassan Yassine, Fotis C Kafatos, Mike A Osta
C-type lectins (CTLs) are a family of proteins that share a common structural motif, the carbohydrate recognition domain, and may act as receptors in pathogen recognition. Indeed, some vertebrate CTLs, particularly the collectins, are unequivocally implicated in the innate immune response to certain microbes. Although studies in insects and other invertebrates have described CTL activation of effector immune responses in vitro, the contribution of these CTLs to immune defenses in vivo is still poorly understood...
June 26, 2009: Journal of Biological Chemistry
Hironobu Kouji, Masato Inazu, Tomoko Yamada, Hirohisa Tajima, Tatsuya Aoki, Teruhiko Matsumiya
We examined the molecular and functional characterization of choline uptake in human colon carcinomas using the cell line HT-29. Furthermore, we explored the possible correlation between choline uptake and cell proliferation. Choline uptake was saturable and mediated by a single transport system. Interestingly, removal of Na(+) from the uptake buffer strongly enhanced choline uptake. This increase in component of choline uptake under Na(+)-free conditions was inhibited by a Na(+)/H(+) exchanger 1 (NHE1) inhibitor...
March 1, 2009: Archives of Biochemistry and Biophysics
D J Obbard, Y-M Linton, F M Jiggins, G Yan, T J Little
Anopheles mosquitoes are the primary vectors for malaria in Africa, transmitting the disease to more than 100 million people annually. Recent functional studies have revealed mosquito genes that are crucial for Plasmodium development, but there is presently little understanding of which genes mediate vector competence in the wild, or evolve in response to parasite-mediated selection. Here, we use population genetic approaches to study the strength and mode of natural selection on a suite of mosquito immune system genes, CTL4, CTLMA2, LRIM1, and APL2 (LRRD7), which have been shown to affect Plasmodium development in functional studies...
August 2007: Molecular Ecology
Masatoshi Tomi, Kanako Arai, Masanori Tachikawa, Ken-ichi Hosoya
The purpose of this study was to clarify the mechanism of the inner blood-retinal barrier (inner BRB) transport of choline and examine the choline uptake ability of rat choline transporter-like protein (CTL) 1. The transcript level of CTL1 in a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2) is more than 100-fold greater than that of CTL3 and CTL4, and no expression of organic cation transporter (OCT) mRNA was detected. The apparent influx permeability clearance of [(3)H]choline in the rat retina was found to be 271 microl/(min x g retina)...
November 2007: Neurochemical Research
Anna Cohuet, Mike A Osta, Isabelle Morlais, Parfait H Awono-Ambene, Kristin Michel, Frederic Simard, George K Christophides, Didier Fontenille, Fotis C Kafatos
Parasites that cause malaria must complete a complex life cycle in Anopheles vector mosquitoes in order to be transmitted from human to human. Previous gene-silencing studies have shown the influence of mosquito immunity in controlling the development of Plasmodium. Thus, parasite survival to the oocyst stage increased when the parasite antagonist gene LRIM1 (leucine-rich repeat immune protein 1) of the mosquito was silenced, but decreased when the C-type lectin agonist gene CTL4 or CTLMA2 (CTL mannose binding 2) was silenced...
December 2006: EMBO Reports
Emma Warr, Louis Lambrechts, Jacob C Koella, Catherine Bourgouin, George Dimopoulos
We have performed a global genome expression analysis of mosquito responses to CM-25 Sephadex beads and identified 27 regulated immune genes, including several anti-Plasmodium factors and other components with likely roles in melanization. Silencing of two bead injection responsive genes, TEP1 and LRIM1, which encode proteins known to mediate Plasmodium killing, significantly compromised the ability to melanize the beads. In contrast, silencing of two Plasmodium protective c-type lectins, CTL4 and CTLMA2, did not affect bead melanization...
October 2006: Insect Biochemistry and Molecular Biology
Jennifer Volz, Hans-Michael Müller, Agnieszka Zdanowicz, Fotis C Kafatos, Mike A Osta
Two modes of refractoriness to Plasmodium, ookinete lysis and melanization, are known in the malaria vector, Anopheles gambiae. Melanization, a potent insect immune response, is manifested in a genetically selected refractory strain and in susceptible mosquitoes that are depleted of specific C-type lectins (CTLs). Here we use a systematic in vivo RNA interference-mediated reverse genetic screen and other recent results to define a melanization-regulating genetic module or network. It encompasses at least 14 genes, including those that encode five Easter-like clip domain serine proteases and four Masquerade-like serine protease homologues of the mosquito CLIPB and CLIPA subfamilies respectively...
September 2006: Cellular Microbiology
Eappen G Abraham, Sofia B Pinto, Anil Ghosh, Dana L Vanlandingham, Aidan Budd, Stephen Higgs, Fotis C Kafatos, Marcelo Jacobs-Lorena, Kristin Michel
We have functionally analyzed the orthologous SRPN6 genes from Anopheles stephensi and Anopheles gambiae using phylogenetic, molecular, reverse genetic, and cell biological tools. The results strongly implicate SRPN6 in the innate immune response against Plasmodium. This gene belongs to a mosquito-specific gene cluster including three additional Anopheles serpins. SRPN6 expression is induced by Escherichia coli and both rodent and human malaria parasites. The gene is specifically expressed in midgut cells invaded by Plasmodium ookinetes and in circulating and attached hemocytes...
November 8, 2005: Proceedings of the National Academy of Sciences of the United States of America
Jacques Sany
Rheumatoid arthritis (RA) is a frequent, heterogenous crippling disease. The diagnosis must be made as soon as possible in order to begin quickly the treatment. The improvement of our knowledge in the immunopathology of RA allowed the development of new biotherapies directed against harmful mediators such as TNF alpha and Interleukin 1. With anti-TNF alpha agents excellent clinical and biological results are observed in methotrexate refractory RA patients in 70% of cases. Moreover these drugs are able to stop the X ray evolution of the disease...
2003: Bulletin de L'Académie Nationale de Médecine
Johannes Uhl, Roland Penzel, Consolato Sergi, Jürgen Kopitz, Herwart F Otto, Michael Cantz
The deficiency of the lysosomal neuraminidase (NEU1; sialidase) causes the storage disorder sialidosis with symptoms ranging from eye abnormalities and neurological disturbances to skeletal malformations, mental retardation and early death. Sialidosis patients encompassing a wide spectrum of clinical symptoms were screened for mutations in neu1. We identified the same homozygous interstitial deletion (11 kb) in two patients causing the fusion of exon 10 of CTL4 (New Gene 22; NG22) with the 3'-UTR of neu1. In one patient we found the resulting CTL4/Neu1 fusion transcript, in the other we detected an alternatively spliced CTL4 transcript (retention of intron 9)...
June 19, 2002: FEBS Letters
Stanislaw M Stepkowski, Robert A Kirken, Barton W Trawick, Min Wang, Neelam Tejpal, Mou-Er Wang, Ling Tian, James Clark, Barry D Kahan
BACKGROUND: The various toxicities associated with the general immune suppression resulting from current clinical immunosuppressive therapies continue to plague transplant recipients as well as jeopardize allograft survival. METHODS: The present study utilized allochimeric class I MHC antigens (alpha1hu70-77-RT1.Aa) bearing only four donor RT1.Au polymorphic amino acids (a.a.; His70, Val73, Asn74, and Asn77) superimposed on the recipient RT1.Aa background to induce transplantation tolerance in the rat cardiac transplant model...
April 27, 2002: Transplantation
E P Zhang, S Bulfone-Paus, F Hoffmann
BACKGROUND: The immunoreaction after corneal transplantation is caused by the T cell receptor interacting with the major histocompatibility complex (MHC) receptor of the antigen-presenting cell. The signal is amplified by the CD4 receptor and the costimulatory signal interactions of CD28-B7 and CD40-CD154. We investigated the influence of costimulatory signal blocking on corneal transplant survival in mice. METHODS: Seven groups of 6 BALB/c mice received an orthotopic corneal transplant from C3H mice differing in minor and major MHC and were postoperatively treated as follows: (1) 80 micrograms of CTLA4 fusion protein intraperitoneally (i...
March 2002: Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
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