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https://www.readbyqxmd.com/read/28551826/development-of-an-8-color-antibody-panel-for-functional-phenotyping-of-human-cd8-cytotoxic-t-cells-from-peripheral-blood-mononuclear-cells
#1
Tara Patel, Amy Cunningham, Martha Holland, John Daley, Suzan Lazo, F Stephen Hodi, Mariano Severgnini
The study of CD8 positive cells in peripheral blood has become an essential part of research in the field of cancer immunotherapies, vaccine development, inflammation, autoimmune disease, etc. In this study, an 8-color flow cytometry panel, containing lineage and functional markers, was developed for the identification of CD8+ cytotoxic T cells in previously cryopreserved peripheral blood mononuclear cells from healthy human donors. By studying functional markers in naïve and CD3/CD28 activated T cells we demonstrate that the panel is capable of detecting protein markers corresponding to different T cell activation statuses...
May 27, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28551807/prohibitin-signaling-at-the-kidney-filtration-barrier
#2
Christina Ising, Paul T Brinkkoetter
The kidney filtration barrier consists of three well-defined anatomic layers comprising a fenestrated endothelium, the glomerular basement membrane (GBM) and glomerular epithelial cells, the podocytes. Podocytes are post-mitotic and terminally differentiated cells with primary and secondary processes. The latter are connected by a unique cell-cell contact, the slit diaphragm. Podocytes maintain the GBM and seal the kidney filtration barrier to prevent the onset of proteinuria. Loss of prohibitin-1/2 (PHB1/2) in podocytes results not only in a disturbed mitochondrial structure but also in an increased insulin/IGF-1 signaling leading to mTOR activation and a detrimental metabolic switch...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28551748/anatomy-and-cell-biology-of-autism-spectrum-disorder-lessons-from-human-genetics
#3
Kristel T E Kleijer, Guillaume Huguet, Julie Tastet, Thomas Bourgeron, J P H Burbach
Until recently autism spectrum disorder (ASD) was regarded as a neurodevelopmental condition with unknown causes and pathogenesis. In the footsteps of the revolution of genome technologies and genetics, and with its high degree of heritability, ASD became the first neuropsychiatric disorder for which clues towards molecular and cellular pathogenesis were uncovered by genetic identification of susceptibility genes. Currently several hundreds of risk genes have been assigned, with a recurrence below 1% in the ASD population...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28551733/rt-lamp-assay-an-alternative-approach-for-profiling-of-bovine-heat-shock-protein-70-gene-in-pbmc-cultured-model
#4
Gyanendra Singh Sengar, Rajib Deb, T V Raja, Umesh Singh, Rajiv Kant, V Bhanuprakash, R R Alyethodi, Sushil Kumar, Preetam Verma, Soumendu Chakraborty, Rani Alex, Rani Singh
The purpose of this study is to develop a novel Reverse Transcriptase Loop-mediated isothermal amplification (RT-LAMP) based assay for in vitro profiling of heat shock protein 70 (Hsp70) in bovine peripheral blood mononuclear cell (PBMC) culture model utilizing the absorbance level of magnesium pyrophosphate-a by-product of LAMP reaction. A set of bovine Hsp70 specific RT-LAMP primers were designed to detect the differential absorbance level of magnesium pyrophosphate by-product which signifies the degree of Hsp70 amplification from cDNA of thermally induced cultured cells at different recovery periods...
May 27, 2017: Molecular Biology Reports
https://www.readbyqxmd.com/read/28551413/applying-the-chicken-embryo-chorioallantoic-membrane-assay-to-study-treatment-approaches-in-urothelial-carcinoma
#5
Margaretha A Skowron, Anuja Sathe, Andrea Romano, Michèle J Hoffmann, Wolfgang A Schulz, Gommert A van Koeveringe, Peter Albers, Roman Nawroth, Günter Niegisch
BACKGROUND: Rapid development of novel treatment options demands valid preclinical screening models for urothelial carcinoma (UC). The translational value of high-throughput drug testing using 2-dimensional (2D) cultures is limited while for xenograft models handling efforts and costs often become prohibitive for larger-scale drug testing. Therefore, we investigated to which extent the chicken chorioallantoic membrane (CAM) assay might provide an alternative model to study antineoplastic treatment approaches for UC...
May 25, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28551388/anaplastic-lymphoma-kinase-protein-positive-diffuse-large-b-cell-lymphoma-a-developing-world-experience
#6
Huzaifah Salat, Nasir Ud Din, Tariq Moatter, Naila Kayani, Arsalan Ahmed
Anaplastic lymphoma kinase (ALK) positive diffuse large B-cell lymphoma (ALK+DLBCL) is a rare, distinct and aggressive subtype of non-Hodgkin's lymphoma (NHL). These tumors are considered to be derived from post-germinal center B cells but peculiarly their distinction is based on the fact that they are ALK-positive neoplastic B cells but lack expression of B cell markers (CD19,CD20, CD79a), T cell markers (CD3, CD5) and CD30. Its broad differential diagnosis and similarities to plasmablastic lymphoma, immunoblastic DLBCL, Anaplastic large-cell lymphoma (ALCL) of T-null cell lineage, and poorly differentiated/anaplastic carcinoma pose a grave challenge to physicians with conventional costly treatment for DLBCL failing to yield any clinical or prognostic significance in ALK+DLBCL...
March 6, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28551381/a-specific-mutational-signature-associated-with-dna-8-oxoguanine-persistence-in-mutyh-defective-colorectal-cancer
#7
Alessandra Viel, Alessandro Bruselles, Ettore Meccia, Mara Fornasarig, Michele Quaia, Vincenzo Canzonieri, Eleonora Policicchio, Emanuele Damiano Urso, Marco Agostini, Maurizio Genuardi, Emanuela Lucci-Cordisco, Tiziana Venesio, Aline Martayan, Maria Grazia Diodoro, Lupe Sanchez-Mete, Vittoria Stigliano, Filomena Mazzei, Francesca Grasso, Alessandro Giuliani, Marta Baiocchi, Roberta Maestro, Giuseppe Giannini, Marco Tartaglia, Ludmil B Alexandrov, Margherita Bignami
8-Oxoguanine, a common mutagenic DNA lesion, generates G:C>T:A transversions via mispairing with adenine during DNA replication. When operating normally, the MUTYH DNA glycosylase prevents 8-oxoguanine-related mutagenesis by excising the incorporated adenine. Biallelic MUTYH mutations impair this enzymatic function and are associated with colorectal cancer (CRC) in MUTYH-Associated Polyposis (MAP) syndrome. Here, we perform whole-exome sequencing that reveals a modest mutator phenotype in MAP CRCs compared to sporadic CRC stem cell lines or bulk tumours...
April 13, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28551327/t-cell-transcription-factor-gata-3-is-an-immunophenotypic-marker-of-acute-leukemias-with-t-cell-differentiation
#8
David M Dorfman, Elizabeth A Morgan, Ashley Pelton, Christine Unitt
T cell transcription factor GATA-3, known to play a role in early T cell development and in the development of T cell neoplasms, is expressed at high levels in fetal and adult thymus, as well as in acute leukemias with T-cell differentiation, including T lymphoblastic leukemia/lymphoma (22/22 cases), early T cell precursor (ETP) lymphoblastic leukemia (11/11 cases), and mixed phenotype acute leukemia, T/myeloid (4/5 cases), but only rarely in acute myeloid leukemia/myeloid sarcoma (1/36 cases), and not in B lymphoblastic leukemia (0/16 cases)...
May 24, 2017: Human Pathology
https://www.readbyqxmd.com/read/28551309/ontak-like-human-il-2-fusion-toxin
#9
Zhaohui Wang, Qian Zheng, Huiping Zhang, Roderick T Bronson, Joren C Madsen, David H Sachs, Christene A Huang, Zhirui Wang
Ontak® is a FDA-approved diphtheria toxin-based recombinant fusion toxin for treatment of human CD25(+) cutaneous T cell lymphoma (CTCL). However, it has been discontinued clinically due to the production issue related to the bacterial expression system with difficult purification. Recently we have developed monovalent and bivalent human IL-2 fusion toxins targeting human CD25(+) cells using advanced unique diphtheria toxin resistant yeast Pichia Pastoris expression system. In vitro efficacy characterization using human CD25(+) HUT102/6TG cells demonstrated that both monovalent and bivalent isoforms are potent and the bivalent isoform is approximately two logs more potent than the monovalent isoform...
May 24, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28550816/designing-an-hcv-vaccine-a-unique-convergence-of-prevention-and-therapy
#10
REVIEW
Christopher M Walker
Direct acting antivirals can cure chronic hepatitis C virus (HCV) infection but whether they will reduce global liver disease burden is uncertain. Most chronic infections are undiagnosed and transmission has increased in recent years. The first trial of a preventive vaccine is now underway in humans at risk for HCV infection. It will test the novel hypothesis that T cell-mediated immunity alone can prevent persistent HCV infection. Another vaccine that elicits neutralizing antibodies is at an advanced stage of development...
May 24, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28550730/transplantation-of-aire-overexpressing-bone-marrow-derived-dendritic-cells-delays-the-onset-of-type-1-diabetes
#11
Dongbei Li, Bo Zhao, Yadong Luo, Steven Limbara, Bingjie Zhao, Xueyang Zou, Wei Yang, Yi Li
Autoimmune regulator (Aire) plays an indispensable role in maintaining central immune tolerance by promoting the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), which lead to the deletion of autoreactive T cells or the induction of Tregs and consequently prevent autoimmune disease development. Curing autoimmune diseases has always been a challenge. DC-based immunotherapy represents a new and effective method to establish tolerance...
May 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28550681/antibiotic-associated-manipulation-of-the-gut-microbiota-and-phenotypic-restoration-in-nod-mice
#12
James R Fahey, Bonnie L Lyons, Haiyan L Olekszak, Anthony J Mourino, Jeremy J Ratiu, Jeremy J Racine, Harold D Chapman, David V Serreze, Dina L Baker, N Ken Hendrix
Segmented filamentous bacterium (SFB) a gram-positive, anaerobic, and intestinal commensal organism directly influencesthe development of Th17 helper cells in the small intestine of mice. In NOD mice, SFB colonization interferes with the developmentof type 1 diabetes (T1D), a T-cell-mediated autoimmune disease, suggesting that SFB may influence Th17 cells to inhibit Th1populations associated with the anti-β-cell immune response. This effect is a serious concern for investigators who use NOD micefor diabetes research because the expected incidence of disease decreases markedly when they are colonized by SFB...
May 26, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28550203/socs1-is-a-key-molecule-that-prevents-regulatory-t-cell-plasticity-under-inflammatory-conditions
#13
Reiko Takahashi, Hiroko Nakatsukasa, Shunichi Shiozawa, Akihiko Yoshimura
We previously showed that regulatory T cells (Tregs) from T cell-specific Socs1-deficient mice (Socs1(fl/fl)Lck-Cre(+) mice) easily convert into Th1- or Th17-like cells (ex-Tregs), which lose Foxp3 expression and suppressive functions in vivo. Because Tregs in Socs1(fl/fl)Lck-Cre(+) mice are constantly exposed to a large amount of inflammatory cytokines produced by non-Tregs in vivo, in this study we analyzed Treg-specific Socs1-deficient mice (Socs1(fl/fl)Foxp3(YFP-Cre) mice). These mice developed dermatitis, splenomegaly, and lymphadenopathy that were much milder than those in Socs1(fl/fl)Lck-Cre(+) mice...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550199/comprehensive-approach-for-identifying-the-t-cell-subset-origin-of-cd3-and-cd28-antibody-activated-chimeric-antigen-receptor-modified-t-cells
#14
Michael Schmueck-Henneresse, Bilal Omer, Thomas Shum, Haruko Tashiro, Maksim Mamonkin, Natalia Lapteva, Sandhya Sharma, Lisa Rollins, Gianpietro Dotti, Petra Reinke, Hans-Dieter Volk, Cliona M Rooney
The outcome of therapy with chimeric Ag receptor (CAR)-modified T cells is strongly influenced by the subset origin of the infused T cells. However, because polyclonally activated T cells acquire a largely CD45RO(+)CCR7(-) effector memory phenotype after expansion, regardless of subset origin, it is impossible to know which subsets contribute to the final T cell product. To determine the contribution of naive T cell, memory stem T cell, central memory T cell, effector memory T cell, and terminally differentiated effector T cell populations to the CD3 and CD28-activated CAR-modified T cells that we use for therapy, we followed the fate and function of individually sorted CAR-modified T cell subsets after activation with CD3 and CD28 Abs (CD3/28), transduction and culture alone, or after reconstitution into the relevant subset-depleted population...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550198/host-derived-cd70-suppresses-murine-graft-versus-host-disease-by-limiting-donor-t-cell-expansion-and-effector-function
#15
Nicholas D Leigh, Rachel E O'Neill, Wei Du, Chuan Chen, Jingxin Qiu, Jonathan D Ashwell, Philip L McCarthy, George L Chen, Xuefang Cao
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for hematologic and immunologic diseases. However, graft-versus-host disease (GVHD) may develop when donor-derived T cells recognize and damage genetically distinct normal host tissues. In addition to TCR signaling, costimulatory pathways are involved in T cell activation. CD27 is a TNFR family member expressed on T cells, and its ligand, CD70, is expressed on APCs. The CD27/CD70 costimulatory pathway was shown to be critical for T cell function and survival in viral infection models...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550190/patient-derived-anti-%C3%AE-2gp1-antibodies-recognize-a-peptide-motif-pattern-and-not-a-specific-sequence-of-residues
#16
Philippe de Moerloose, Céline Fickentscher, Françoise Boehlen, Jean-Marie Tiercy, Egbert K O Kruithof, Karim J Brandt
Antiphospholipid antibody syndrome is an autoimmune disease characterized by the presence of so-called antiphospholipid antibodies and clinical manifestations such as recurrent thromboembolic or pregnancy complications. Although the main antigenic determinant for antiphospholipid antibodies has been identified as the beta-2-glycoprotein 1 (β2GP1), the precise epitope recognized by antiphospholipid antibodies still remains largely unknown. In the present study, we wanted to identify a sequence in the domain I of β2GP1 able to induce the proliferation of CD4+ T cells isolated from antiphospholipid antibody syndrome patients but not from healthy donors and to interact with antiphospholipid antibodies...
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28550184/reduced-hematopoietic-stem-cells-frequency-predicts-outcome-in-acute-myeloid-leukemia
#17
Wenwen Wang, Thomas Stiehl, Simon Raffel, Van T Hoang, Isabel Hoffmann, Laura Poisa-Beiro, Borhan R Saeed, Rachel Blume, Linda Manta, Volker Eckstein, Tilmann Bochtler, Patrick Wuchter, Marieke Essers, Anna Jauch, Andreas Trumpp, Anna Marciniak-Czochra, Anthony D Ho, Christoph Lutz
In patients with acute myeloid leukemia and low percentages of aldehyde-dehydrogenase-positive cells, non-leukemic hematopoietic stem cells can be separated from leukemic cells. By relating hematopoietic stem cell frequencies to outcome we detected poor overall- and disease-free survival of patients with low hematopoietic stem cell frequencies. Serial analysis of matched diagnostic and follow-up samples further demonstrated that hematopoietic stem cells increased after chemotherapy in patients that achieved durable remissions...
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28550122/the-blood-borne-sialyltransferase-st6gal-1-is-a-negative-systemic-regulator-of-granulopoiesis
#18
Christopher W L Dougher, Alexander Buffone, Michael J Nemeth, Mehrab Nasirikenari, Eric E Irons, Paul N Bogner, Joseph T Y Lau
Responding to systemic demands in producing and replenishing end-effector blood cells is predicated on the appropriate delivery and interpretation of extrinsic signals to the HSPCs. The data presented herein implicate the systemic, extracellular form of the glycosyltransferase ST6Gal-1 in the regulation of late-stage neutrophil development. ST6Gal-1 is typically a membrane-bound enzyme sequestered within the intracellular secretory apparatus, but an extracellular form is released into the blood from the liver...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28550121/bcl6-represses-antiviral-resistance-in-follicular-t-helper-cells
#19
Tohti Amet, Young Min Son, Li Jiang, In Su Cheon, Su Huang, Samir K Gupta, Alexander L Dent, Luis J Montaner, Qigui Yu, Jie Sun
Follicular Th (Tfh) cells are a distinct subset of Th cells that help B cells produce class-switched antibodies. Studies have demonstrated that Tfh cells are highly prone to HIV infection and replication. However, the molecular mechanisms underlying this phenomenon are largely unclear. Here, we show that murine and human Tfh cells have diminished constitutive expression of IFN-stimulated genes (ISGs) inclusive of antiviral resistance factor MX dynamin-like GTPase 2 (MX2) and IFN-induced transmembrane 3 (IFITM3) compared with non-Tfh cells...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28550117/comparative-exploration-of-multidimensional-flow-cytometry-software-a-model-approach-evaluating-t-cell-polyfunctional-behavior
#20
Timothy T Spear, Michael I Nishimura, Patricia E Simms
Advancement in flow cytometry reagents and instrumentation has allowed for simultaneous analysis of large numbers of lineage/functional immune cell markers. Highly complex datasets generated by polychromatic flow cytometry require proper analytical software to answer investigators' questions. A problem among many investigators and flow cytometry Shared Resource Laboratories (SRLs), including our own, is a lack of access to a flow cytometry-knowledgeable bioinformatics team, making it difficult to learn and choose appropriate analysis tool(s)...
May 26, 2017: Journal of Leukocyte Biology
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