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https://www.readbyqxmd.com/read/28645940/t-cell-receptors-for-clinical-therapy-in-vitro-assessment-of-toxicity-risk
#1
Andre Kunert, Matthias Obenaus, Cor Hj Lamers, Thomas Blankenstein, Reno Debets
Adoptive therapy with T cell receptor (TCR)-engineered T cells has shown promising results in the treatment of patients with tumors, and the number of TCRs amenable for clinical testing is expanding rapidly. Notably, adoptive therapy with T cells is challenged by treatment-related side effects, which calls for cautious selection of target antigens and TCRs that goes beyond their mere ability to induce high T cell reactivity. Here, we propose a sequence of in vitro assays to improve selection of TCRs, and exemplify risk assessments of on-target as well as off-target toxicities using TCRs directed against Cancer Germline Antigens...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28645930/genomic-and-non-genomic-effects-of-androgens-in-the-cardiovascular-system-clinical-implications
#2
REVIEW
Angela K Lucas Herald, Rheure Alves-Lopes, Augusto C Montezano, S Faisal Ahmed, Rhian M Touyz
The principle steroidal androgens are testosterone and its metabolite 5α-dihydrotestosterone (DHT), which is converted from testosterone by the enzyme 5α-reductase. Through the classic pathway with androgens crossing the plasma membrane and binding to the androgen receptor (AR) or via mechanisms independent of the ligand-dependent transactivation function of nuclear receptors, testosterone induces genomic and non-genomic effects respectively. AR is widely distributed in several tissues, including vascular endothelial and smooth muscle cells...
July 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28639251/regulation-of-the-extracellular-serpina5-protein-c-inhibitor-penetration-through-cellular-membranes
#3
Felix C Wahlmüller, Hanjiang Yang, Margareta Furtmüller, Margarethe Geiger
It is generally accepted that the phospholipid bilayer of the cell membrane is impermeable for proteins and peptides and that these molecules require special mechanisms for their transport from the extra- to the intracellular space. Recently there is increasing evidence that certain proteins/peptides can also directly cross the phospholipid membrane. SERPINA5 (protein C inhibitor) is a secreted protease inhibitor with broad protease reactivity and wide tissue distribution. It binds glycosaminoglycans and certain phospoholipids, which can modulate its inhibitory activity...
June 22, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28624515/development-of-selective-androgen-receptor-modulators-sarms
#4
REVIEW
Ramesh Narayanan, Christopher C Coss, James T Dalton
The Androgen Receptor (AR), a member of the steroid hormone receptor family, plays important roles in the physiology and pathology of diverse tissues. AR ligands, which include circulating testosterone and locally synthesized dihydrotestosterone, bind to and activate the AR to elicit their effects. Ubiquitous expression of the AR, metabolism and cross reactivity with other receptors limit broad therapeutic utilization of steroidal androgens. However, the discovery of selective androgen receptor modulators (SARMs) and other tissue-selective nuclear hormone receptor modulators that activate their cognate receptors in a tissue-selective manner provides an opportunity to promote the beneficial effects of androgens and other hormones in target tissues with greatly reduced unwanted side-effects...
June 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28613414/the-arg-phe-amide-peptide-26rfa-qrfp-and-its-receptor-iuphar-review
#5
REVIEW
Jérôme Leprince, Didier Bagnol, Ronan Bureau, Shoji Fukusumi, Riccarda Granata, Shuji Hinuma, Dan Larhammar, Stefany Primeaux, Jana Sopkova-de Oliveiras Santos, Kazuyoshi Tsutsui, Kazuyoshi Ukena, Hubert Vaudry
26RFa is an RFamide neuropeptide that was first isolated from the brain of the European green frog on the basis of a cross-reactivity with antibodies raised against bovine NPFF. 26RFa and its N-terminally extended form QRFP have been identified as cognate ligands of the former orphan receptor GPR103, now renamed QRFPR. The 26RFa/QRFP precursor has been characterized in various mammalian and non-mammalian species. In the brain of mammals, including human, 26RFa/QRFP mRNA is almost exclusively expressed in hypothalamic nuclei...
June 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28595595/multiplex-detection-in-tonsillar-tissue-of-all-known-human-polyomaviruses
#6
Mohammadreza Sadeghi, Yilin Wang, Torbjörn Ramqvist, Leena-Maija Aaltonen, Lari Pyöriä, Mari Toppinen, Maria Söderlund-Venermo, Klaus Hedman
BACKGROUND: In the past few years, eleven new human viruses have joined the two previously known members JCPyV and BKPyV of the Polyomaviridae family, by virtue of molecular methods. Serology data suggest that infections with human polyomaviruses (HPyVs) occur since childhood and the viruses are widespread in the general population. However, the viral persistence sites and transmission routes are by and large unknown. Our previous studies demonstrated that the four new HPyVs - KIPyV, WUPyV, MCPyV and TSPyV - were present in the tonsils, and suggested lymphoid tissue as a persistent site of these emerging human viruses...
June 8, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28583232/effect-of-topical-beclomethasone-on-inflammatory-markers-in-adults-with-eosinophilic-esophagitis-a-pilot-study
#7
Neeti Bhardwaj, Faoud Ishmael, Erik Lehman, Deborah Bethards, Francesca Ruggiero, Gisoo Ghaffari
BACKGROUND: Topical corticosteroids have proven efficacy in the treatment of eosinophilic esophagitis (EoE) and are considered the cornerstone of therapy. OBJECTIVE: To evaluate the effect of topical beclomethasone dipropionate (BDP) therapy on clinical outcomes, esophageal eosinophilia, and other markers of inflammation in patients with EoE. METHODS: Nine subjects with a biopsy-proven diagnosis of EoE were enrolled. In a cross-over design, the subjects were randomly assigned to a sequence of BDP and placebo...
June 1, 2017: Allergy & Rhinology
https://www.readbyqxmd.com/read/28535870/age-associated-b-cells-abc-inhibit-b-lymphopoiesis-and-alter-antibody-repertoires-in-old-age
#8
Richard L Riley, Kelly Khomtchouk, Bonnie B Blomberg
With old age (∼2y old), mice show substantial differences in B cell composition within the lymphoid tissues. In particular, a novel subset of IgM(+) CD21/35(lo/-) CD23(-) mature B cells, the age-associated B cells or ABC, increases numerically and proportionately. This occurs at the expense of other B cell subsets, including B2 follicular B cells in spleen and recirculating primary B cells in bone marrow. Our studies suggest that ABC have a distinctive antibody repertoire, as evidenced by relatively high reactivity to the self-antigens phosphorylcholine (PC) and malondialdehyde (MDA)...
April 26, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28528339/molecular-diagnosis-of-tubercular-lymphadenopathy-from-fine-needle-aspirates-in-pediatric-patients
#9
Vivek Gupta, Arvind Bhake
OBJECTIVES: The diagnosis of peripheral tubercular lymphadenopathy (TBLN) in pediatric patients is often a challenge because features evident on fine-needle aspiration cytology (FNAC) or tissue biopsy can be deceptive for the reason that they result from an immunological response. This study aimed to evaluate polymerase chain reaction (PCR) for Mycobacterium tuberculosis complex (MTBC) in pediatric patients under clinical suspicion for TBLN and to assess its role in the evaluation of cases cytodiagnosed as reactive lymphoid hyperplasia...
2017: Acta Cytologica
https://www.readbyqxmd.com/read/28518087/multimer-page-a-method-for-capturing-and-resolving-protein-complexes-in-biological-samples
#10
Tyler Rhinesmith, Bryan A Killinger, Akhil Sharma, Anna Moszczynska
There are many well-developed methods for purifying and studying single proteins and peptides. However, most cellular functions are carried out by networks of interacting protein complexes, which are often difficult to investigate because their binding is non-covalent and easily perturbed by purification techniques. This work describes a method of stabilizing and separating native protein complexes from unmodified tissue using two-dimensional polyacrylamide gel electrophoresis. Tissue lysate is loaded onto a non-denaturing blue-native polyacrylamide gel, then an electric current is applied until the protein migrates a short distance into the gel...
May 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28513711/a-novel-approach-for-fabricating-highly-tunable-and-fluffy-bioinspired-3d-poly-vinyl-alcohol-pva-fiber-scaffolds
#11
Sunanda Roy, Shreyas Kuddannaya, Tanya Das, Heng Yeong Lee, Jacob Lim, Xiao 'Matthew' Hu, Yue Chee Yoon, Jaehwan Kim
The excellent biocompatibility, biodegradability and chemo-thermal stability of poly(vinyl alcohol) (PVA) have been harnessed in diverse practical applications. These properties have motivated the fabrication of high performance PVA based nanofibers with adequate control over the micro and nano-architectures and surface chemical interactions. However, the high water solubility and hydrophilicity of the PVA polymer limits the application of the electrospun PVA nanofibers in aqueous environments owing to instantaneous dissolution...
June 1, 2017: Nanoscale
https://www.readbyqxmd.com/read/28510696/autologous-adipose-derived-tissue-matrix-part-ii-implantation-biology
#12
Stephen A Schendel
Background: In part 1 of this study it was shown that liposuctioned fat could be a sufficient source of autologous collagen for use as a filler or in reconstruction. The collagen composition in liposuctioned fat was shown to form a cross-linked helical matrix composed of types II, III, and IV. Additionally, viable adipocytes and fibroblasts among other cells were found. Objectives: The purpose of this research was to study the biology of this matrix after subsequent implantation compared to Juvederm (Allergan, Parsippany, NJ) common soft tissue filler...
May 16, 2017: Aesthetic Surgery Journal
https://www.readbyqxmd.com/read/28504684/fully-automated-5-plex-fluorescent-immunohistochemistry-with-tyramide-signal-amplification-and-same-species-antibodies
#13
Wenjun Zhang, Antony Hubbard, Tobin Jones, Adriana Racolta, Srabani Bhaumik, Nick Cummins, Liping Zhang, Karl Garsha, Frank Ventura, Mark R Lefever, Zhenqiang Lu, John K Hurley, William A Day, Lidija Pestic-Dragovich, Larry E Morrison, Lei Tang
The ability to simultaneously visualize the presence, abundance, location and functional state of many targets in cells and tissues has been described as a true next-generation approach in immunohistochemistry (IHC). A typical requirement for multiplex IHC (mIHC) is the use of different animal species for each primary (1°Ab) and secondary (2°Ab) antibody pair. Although 1°Abs from different species have been used with differently labeled species-specific 2°Abs, quite often the appropriate combination of antibodies is not available...
May 15, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28496443/higher-levels-of-secretory-iga-are-associated-with-low-disease-activity-index-in-patients-with-reactive-arthritis-and-undifferentiated-spondyloarthritis
#14
Fabián Salas-Cuestas, Wilson Bautista-Molano, Juan M Bello-Gualtero, Ivonne Arias, Diana Marcela Castillo, Lorena Chila-Moreno, Rafael Valle-Oñate, Daniel Herrera, Consuelo Romero-Sánchez
INTRODUCTION: Both reactive arthritis (ReA) and undifferentiated spondyloarthritis (uSpA) belong to the group of autoinflammatory diseases called spondyloarthritis (SpA). Hypotheses have been proposed about a relationship between the intestinal mucosa and inflammation of joint tissues. The role of immunoglobulin IgA or secretory immunoglobulin A (SIgA) in the inflammatory and/or clinical activity of patients with SpA remains poorly understood. OBJECTIVE: To evaluate the status of total IgA and SIgA, and the association among the levels of SIgA, IgA, IgA anti-Chlamydia trachomatis, and anti-Shigella spp...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28493527/characterization-of-a-sandwich-elisa-for-the-quantification-of%C3%A2-all-human-periostin-isoforms
#15
Elisabeth Gadermaier, Manfred Tesarz, Andreea Ana-Maria Suciu, Jacqueline Wallwitz, Gabriela Berg, Gottfried Himmler
BACKGROUND: Periostin (osteoblast-specific factor OSF-2) is a secreted protein occurring in seven known isoforms, and it is involved in a variety of biological processes in osteology, tissue repair, oncology, cardiovascular and respiratory systems or allergic manifestations. To analyze functional aspects of periostin, or the ability of periostin as potential biomarker in physiological and pathological conditions, there is the need for a precise, well-characterized assay that detects periostin in peripheral blood...
May 11, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28489940/isolation-and-characterization-of-canine-perivascular-stem-stromal-cells-for-bone-tissue-engineering
#16
Aaron W James, Xinli Zhang, Mihaela Crisan, Winters R Hardy, Pei Liang, Carolyn A Meyers, Sonja Lobo, Venu Lagishetty, Martin K Childers, Greg Asatrian, Catherine Ding, Yu-Hsin Yen, Erin Zou, Kang Ting, Bruno Peault, Chia Soo
For over 15 years, human subcutaneous adipose tissue has been recognized as a rich source of tissue resident mesenchymal stem/stromal cells (MSC). The isolation of perivascular progenitor cells from human adipose tissue by a cell sorting strategy was first published in 2008. Since this time, the interest in using pericytes and related perivascular stem/stromal cell (PSC) populations for tissue engineering has significantly increased. Here, we describe a set of experiments identifying, isolating and characterizing PSC from canine tissue (N = 12 canine adipose tissue samples)...
2017: PloS One
https://www.readbyqxmd.com/read/28483490/nano-sized-iron-particles-may-induce-multiple-pathways-of-cell-death-following-generation-of-mistranscripted-rna-in-human-corneal-epithelial-cells
#17
Eun-Jung Park, Jae-Byoung Chae, Seuyoung Kang, Jungmook Lyu, Uiseok Jeong, Changjoo Yeom, Younghun Kim, Jaerak Chang
Iron is closely associated with an ambient particulate matters-induced inflammatory response, and the cornea that covers the front of the eye, is among tissues exposed directly to ambient particulate matters. Prior to this study, we confirmed that nano-sized iron particles (FeNPs) can penetrate the cornea. Thus, we identified the toxic mechanism of FeNPs using human corneal epithelial cells. At 24h after exposure, FeNPs located inside autophagosome-like vacuoles or freely within human corneal epithelial cells...
May 5, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28482788/defensive-and-offensive-cross-reactive-antibodies-elicited-by-pathogens-the-good-the-bad-and-the-ugly
#18
Daria Augustyniak, Grażyna Majkowska-Skrobek, Justyna Roszkowiak, Agata Dorotkiewicz-Jach
Understanding how immunity to pathogens develops is crucial for progress in the quest for effective vaccines. Intraspecies and interspecies cross-reacting antibodies are produced in high frequency against immune-relevant and shared microbial epitopes. It has been confirmed that cross-reactive antigens may have a crucial role in natural epidemiology to a particular infection and that cross-protection may influence the outcome of natural infections. On the other hand, the action of cross-reactive antibodies may be very harmful for the host...
May 7, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28478688/gene-delivery-of-activated-factor-vii-using-alternative-adeno-associated-virus-serotype-improves-hemostasis-in-hemophiliac-mice-with-fviii-inhibitors-and-adeno-associated-virus-neutralizing-antibodies
#19
Junjiang Sun, Baolai Hua, Xiaojing Chen, Richard J Samulski, Chengwen Li
While therapeutic expression of coagulation factors from adeno-associated virus (AAV) vectors has been successfully achieved in patients with hemophilia, neutralizing antibodies to the vector and inhibitory antibodies to the transgene severely limit efficacy. Indeed, approximately 40% of mice transduced with human factor VIII using the AAV8 serotype developed inhibitory antibodies to factor VIII (FVIII inhibitor), as well as extremely high titers (≥1:500) of neutralizing antibodies to AAV8. To correct hemophilia in these mice, AAV9, a serotype with low in vitro cross-reactivity (≤1:5) to anti-AAV8, was used to deliver mouse-activated factor VII (mFVIIa)...
May 5, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28475122/harnessing-local-immunity-for-an-effective-universal-swine-influenza-vaccine
#20
REVIEW
Elma Tchilian, Barbara Holzer
Influenza A virus infections are a global health threat to humans and are endemic in pigs, contributing to decreased weight gain and suboptimal reproductive performance. Pigs are also a source of new viruses of mixed swine, avian, and human origin, potentially capable of initiating human pandemics. Current inactivated vaccines induce neutralising antibody against the immunising strain but rapid escape occurs through antigenic drift of the surface glycoproteins. However, it is known that prior infection provides a degree of cross-protective immunity mediated by cellular immune mechanisms directed at the more conserved internal viral proteins...
May 5, 2017: Viruses
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