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https://www.readbyqxmd.com/read/27925405/animal-to-human-dose-translation-of-obiltoxaximab-for-treatment-of-inhalational-anthrax-under-the-us-fda-animal-rule
#1
C F Nagy, J Mondick, N Serbina, L S Casey, S E Carpenter, J French, R Guttendorf
Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax under the US Food and Drug Administration's (FDA) Animal Rule. The human dose was selected and justified by comparing observed obiltoxaximab exposures in healthy and infected New Zealand White rabbits and cynomolgus macaques to observed exposures in healthy humans, to simulated exposures in healthy and infected humans, and to serum PA levels in infected animals. In humans, at 16 mg/kg intravenous, obiltoxaximab AUC was >2 times that in animals, while maximum serum concentrations were comparable to those in animals and were maintained in excess of the concentration required for PA neutralization in infected animals for 2-3 weeks...
December 7, 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27922202/current-practices-for-screening-consent-and-care-of-related-donors-in-france-haematopoietic-stem-cell-transplantation-coordinator-nurses-perceptions
#2
A Polomeni, C Bompoint, A Gomez, E Brissot, A Ruggeri, R Belhocine, M Mohty
Haematopoietic stem cell transplantation-coordinating nurses (HSCT-CNs) play an important role in informing related donors (RDs) and in organising human leucocyte antigen (HLA) tests, pre-donation workup and stem cells collection. Our pilot study aimed to explore French HSCT-CNs' perceptions of RD care issues. Twenty-nine French HSCT adult units were sent a questionnaire on the subject of donation procedures, HSCT-CNs' data and their professional experience of related donation issues. Twenty-two HSCT-CNs returned a completed questionnaire, and 90% of HSCT units were involved to some degree in both patient and donor care...
December 6, 2016: European Journal of Cancer Care
https://www.readbyqxmd.com/read/27921303/eosinophils-from-eosinophilic-oesophagitis-patients-have-t-cell-suppressive-capacity-and-express-foxp3
#3
C Lingblom, J Wallander, M Ingelsten, H Bergquist, M Bove, R Saalman, A Welin, C Wennerås
Eosinophilic esophagitis (EoE) is an antigen-driven T cell-mediated chronic inflammatory disease where food and environmental antigens are thought to have a role. Human eosinophils express the immunoregulatory protein galectin-10 and have T cell suppressive capacity similar to regulatory T cells (Tregs ). We hypothesized that one function of eosinophils in EoE might be to regulate the T cell-driven inflammation in the oesophagus. This was tested by evaluating the suppressive capacity of eosinophils isolated from the blood of adult EoE patients in a mixed lymphocyte reaction...
November 5, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27920218/a-molecular-basis-for-the-presentation-of-phosphorylated-peptides-by-hla-b-antigens
#4
Adán Alpízar, Fabio Marino, Antonio Ramos-Fernández, Manuel Lombardía, Anita Jeko, Florencio Pazos, Alberto Paradela, César Santiago, Albert J R Heck, Miguel Marcilla
As aberrant protein phosphorylation is a hallmark of tumor cells, the display of tumor-specific phosphopeptides by Human Leukocyte Antigen (HLA) class I molecules can be exploited in the treatment of cancer by T-cell-based immunotherapy. Yet, the characterization and prediction of HLA-I phospholigands is challenging as the molecular determinants of the presentation of such post-translationally modified peptides are not fully understood. Here, we employed a peptidomic workflow to identify 256 unique phosphorylated ligands associated with HLA-B*40, -B*27, -B*39 or -B*07...
December 5, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27913644/the-impact-of-established-immunoregulatory-networks-on-vaccine-efficacy-and-the-development-of-immunity-to-malaria
#5
REVIEW
Marcela Montes de Oca, Michael F Good, James S McCarthy, Christian R Engwerda
The development of vaccines to protect against parasites is difficult, in large part due to complex host-parasite interactions that have evolved over millennia. Parasitic factors such as antigenic variation and host factors such as age, transmission intensity, and genetic influences are all thought to contribute to the limited efficacy of parasite vaccines. A developing theme in field studies investigating antiparasitic immunity is the emergence, establishment, and maintenance of immunoregulatory networks that shape the immune responses to new infections, as well as vaccines, thereby influencing disease outcome...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27911124/the-impact-of-interferon-alpha2-on-hla-genes-in-patients-with-polycythemia-vera-and-related-neoplasms
#6
Vibe Skov, Caroline Hasselbalch Riley, Mads Thomassen, Lasse Kjær, Thomas Stauffer Larsen, Ole Weis Bjerrum, Torben A Kruse, Hans Carl Hasselbalch
Gene expression profiling in Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have unraveled significant deregulation of several immune and inflammation genes of potential importance for clonal evolution. Other mechanisms might be downregulation of major histocompatibility class I and II genes used by tumor cells to escape antitumor T-cell-mediated immune responses. Several genes encoding human leukocyte antigen (HLA) class I and II molecules have been shown to be significantly downregulated...
December 2, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27910249/the-hla-a-b-and-drb1-polymorphism-in-a-large-dataset-of-south-brazil-bone-marrow-donors-from-rio-grande-do-sul
#7
J A Boquett, J M Nunes, S Buhler, M Z de Oliveira, L F Jobim, M Jobim, N J R Fagundes, L Schüler-Faccini, A Sanchez-Mazas
Human leukocyte antigen (HLA) genes are very informative in population genetics studies and their variability has been widely used to reconstruct the history of geographic and/or demographic expansions of human populations. The characterization of HLA diversity at the population level is also fundamental in clinical studies, particularly for bone marrow transplantation programs. In this study, we investigated the HLA molecular variation in Rio Grande do Sul, South Brazil, in order to identify possible regional differences across this state...
December 2, 2016: HLA
https://www.readbyqxmd.com/read/27908497/the-use-of-an-inkjet-injection-technique-in-immunoassays-by-quantitative-on-line-electrophoretically-mediated-microanalysis
#8
Weifei Zhang, Sifeng Mao, Jianmin Yang, Hulie Zeng, Hizuru Nakajima, Shungo Kato, Katsumi Uchiyama
The paper describes a new online quantitative electrophoretically mediated microanalysis (EMMA) for use in immunoassays based on the unique drop-by-drop introduction of a sample by means of an inkjet for capillary electrophoresis (CE). Plugs of a fluorescein-labeled antibody (Anti-humanIgG-DyL550) and human IgG were alternately injected into a capillary using the inkjet, followed by the merging of the plugs and the subsequent immune reaction. The antigen-antibody complex that was formed in the merged zone was then separated by CE...
November 23, 2016: Journal of Chromatography. A
https://www.readbyqxmd.com/read/27905107/co-operative-suppression-of-inflammatory-responses-in-human-dendritic-cells-by-plant-proanthocyanidins-and-products-from-the-parasitic-nematode-trichuris-suis
#9
Andrew R Williams, Elsenoor J Klaver, Lisa C Laan, Aina Ramsay, Christos Fryganas, Rolf Difborg, Helene Kringel, Jess D Reed, Irene Mueller-Harvey, Søren Skov, Irma van Die, Stig M Thamsborg
Interactions between dendritic cells (DCs) and environmental, dietary and pathogen antigens play a key role in immune homeostasis and regulation of inflammation. Dietary polyphenols such as proanthocyanidins (PAC) may reduce inflammation, and we therefore hypothesized that PAC may suppress lipopolysaccharide (LPS) -induced responses in human DCs and subsequent T helper type 1 (Th1) -type responses in naive T cells. Moreover, we proposed that, because DCs are likely to be exposed to multiple stimuli, the activity of PAC may synergise with other bioactive molecules that have anti-inflammatory activity, e...
November 7, 2016: Immunology
https://www.readbyqxmd.com/read/27903863/internalization-of-secreted-antigen-targeted-antibodies-by-the-neonatal-fc-receptor-for-precision-imaging-of-the-androgen-receptor-axis
#10
Daniel L J Thorek, Philip A Watson, Sang-Gyu Lee, Anson T Ku, Stylianos Bournazos, Katharina Braun, Kwanghee Kim, Kjell Sjöström, Michael G Doran, Urpo Lamminmäki, Elmer Santos, Darren Veach, Mesruh Turkekul, Emily Casey, Jason S Lewis, Diane S Abou, Marise R H van Voss, Peter T Scardino, Sven-Erik Strand, Mary L Alpaugh, Howard I Scher, Hans Lilja, Steven M Larson, David Ulmert
Targeting the androgen receptor (AR) pathway prolongs survival in patients with prostate cancer, but resistance rapidly develops. Understanding this resistance is confounded by a lack of noninvasive means to assess AR activity in vivo. We report intracellular accumulation of a secreted antigen-targeted antibody (SATA) that can be used to characterize disease, guide therapy, and monitor response. AR-regulated human kallikrein-related peptidase 2 (free hK2) is a prostate tissue-specific antigen produced in prostate cancer and androgen-stimulated breast cancer cells...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27894716/characterization-of-guinea-pig-t-cell-responses-elicited-after-ep-assisted-delivery-of-dna-vaccines-to-the-skin
#11
Katherine Schultheis, Hubert Schaefer, Bryan S Yung, Janet Oh, Karuppiah Muthumani, Laurent Humeau, Kate E Broderick, Trevor R F Smith
The skin is an ideal target tissue for vaccine delivery for a number of reasons. It is highly accessible, and most importantly, enriched in professional antigen presenting cells. Possessing strong similarities to human skin physiology and displaying a defined epidermis, the guinea pig is an appropriate model to study epidermal delivery of vaccine. However, whilst we have characterized the humoral responses in the guinea pig associated with skin vaccine protocols we have yet to investigate the T cell responses...
November 25, 2016: Vaccine
https://www.readbyqxmd.com/read/27894367/potential-immunological-markers-for-diagnosis-of-human-strongyloidiasis-using-heterologous-antigens
#12
M A Corral, F M Paula, D M C L Meisel, V L P Castilho, E M N Gonçalves, D Levy, S P Bydlowski, P P Chieffi, W Castro-Borges, R C B Gryschek
Strongyloides venezuelensis is a parasitic nematode of rodents that is frequently used to obtain heterologous antigens for immunological diagnosis of human strongyloidiasis. The aim of this study was to identify antigens from filariform larvae of S. venezuelensis for immunodiagnosis of human strongyloidiasis. Soluble and membrane fractions from filariform larvae of S. venezuelensis were obtained in phosphate saline (SS and SM) and in Tris-HCl buffer (TS and TM), and were analysed by Western blotting. Different antigenic components were recognized by IgG antibodies from the sera of strongyloidiasis patients...
November 29, 2016: Parasitology
https://www.readbyqxmd.com/read/27893426/sublethal-exposure-to-alpha-radiation-223ra-dichloride-enhances-various-carcinomas-sensitivity-to-lysis-by-antigen-specific-cytotoxic-t-lymphocytes-through-calreticulin-mediated-immunogenic-modulation
#13
Anthony S Malamas, Sofia R Gameiro, Karin M Knudson, James W Hodge
Radium-223 dichloride (Xofigo®; 223Ra) is an alpha-emitting radiopharmaceutical FDA-approved for the treatment of bone metastases in patients with advanced castration-resistant prostate cancer. It is also being examined clinically in patients with breast and lung carcinoma and patients with multiple myeloma. As with other forms of radiation, the aim of 223Ra is to reduce tumor burden by directly killing tumor cells. External beam (photon) and proton radiation have been shown to augment tumor sensitivity to antigen-specific CD8+ cytotoxic T lymphocytes (CTLs)...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27887864/optimization-of-cgmp-purification-and-expansion-of-umbilical-cord-blood-derived-t-regulatory-cells-in-support-of-first-in-human-clinical-trials
#14
David H McKenna, Darin Sumstad, Diane M Kadidlo, Bjorn Batdorf, Colin J Lord, Sarah C Merkel, Christine M Koellner, Julie M Curtsinger, Carl H June, James L Riley, Bruce L Levine, Jeffrey S Miller, Claudio G Brunstein, John E Wagner, Bruce R Blazar, Keli L Hippen
BACKGROUND AIMS: Thymic-derived regulatory T cells (tTreg) are critical regulators of the immune system. Adoptive tTreg transfer is a curative therapy for murine models of autoimmunity, graft rejection, and graft-versus-host disease (GVHD). We previously completed a "first-in-human" clinical trial using in vitro expanded umbilical cord blood (UCB)-derived tTreg to prevent GVHD in patients undergoing UCB hematopoietic stem cell transplantation (HSCT). tTreg were safe and demonstrated clinical efficacy, but low yield prevented further dose escalation...
November 22, 2016: Cytotherapy
https://www.readbyqxmd.com/read/27886660/evaluation-of-the-safety-and-adjuvant-effect-of-a-detoxified-listeriolysin-o-mutant-on-the-humoral-response-to-dengue-virus-antigens
#15
K G Hernández-Flores, A L Calderón-Garcidueñas, G Mellado-Sánchez, R Ruiz-Ramos, L A Sánchez-Vargas, P Thomas-Dupont, I Y Izaguirre-Hernández, J Téllez-Sosa, J Martínez-Barnetche, L Wood, Y Paterson, L Cedillo-Barrón, O López-Franco, H Vivanco-Cid
Listeriolysin O (LLO) has been proposed as a potential carrier or adjuvant molecule in the vaccination field. However, the cytotoxic and pro-apoptotic effects of LLO are the major limitations for this purpose. Here, we have performed a preclinical safety evaluation and characterized a new potential adjuvant application for a non-cytolytic LLO mutant (dtLLO) to enhance and modulate the immune response against the envelope (E) protein from Dengue virus. In addition, we have studied the adjuvant effects of dtLLO on human immune cells and the role of membrane cholesterol for the binding and the pro-inflammatory property of the toxoid...
November 25, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27881906/genetic-and-immunohistochemical-analysis-of-hspa5-in-mouse-and-human-retinas
#16
Sumana R Chintalapudi, XiaoFei Wang, Huiling Li, Yin H Chan Lau, Robert W Williams, Monica M Jablonski
PURPOSE: Photoreceptor degenerative diseases are among the leading causes of vision loss. Although the causative genetic mutations are often known, mechanisms leading to photoreceptor degeneration remain poorly defined. We have previously demonstrated that the photoreceptor membrane-associated protein XAP-1 antigen is a product of the HSPA5 gene. In this study, we used systems genetic methods, statistical modeling, and immunostaining to identify and analyze candidate genes that modulate Hspa5 expression in the retina...
2016: Molecular Vision
https://www.readbyqxmd.com/read/27881839/a-polymorphism-in-human-mr1-is-associated-with-mrna-expression-and-susceptibility-to-tuberculosis
#17
C Seshadri, N T T Thuong, N T H Mai, N D Bang, T T H Chau, D M Lewinsohn, G E Thwaites, S J Dunstan, T R Hawn
The MR1 antigen-presenting system is conserved among mammals and enables T cells to recognize small molecules produced by bacterial pathogens, including Mycobacterium tuberculosis (M.tb). However, it is not known whether MR1-mediated antigen presentation is important for protective immunity against mycobacterial disease. We hypothesized that genetic control of MR1 expression correlates with clinical outcomes of tuberculosis infection. We performed an MR1 candidate gene association study and identified an intronic single-nucleotide polymorphism (rs1052632) that was significantly associated with susceptibility to tuberculosis in a discovery and validation cohort of Vietnamese adults with tuberculosis...
November 24, 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27875685/progressive-disseminated-histoplasmosis-a-systematic-review-on-the-performance-of-non-culture-based-diagnostic-tests
#18
Diego R Falci, Elias R Hoffmann, Diego D Paskulin, Alessandro C Pasqualotto
The diagnosis of progressive disseminated histoplasmosis is often a challenge to clinicians, especially due to the low sensitivity and long turnaround time of the classic diagnostic methods. In recent years, studies involving a variety of non-culture-based diagnostic tests have been published in the literature. The aim of this paper is to perform a systematic review by selecting articles evaluating non-culture-based diagnostic methods in the diagnosis of progressive disseminated histoplasmosis. We searched for articles evaluating detection of antibody, antigens, and DNA methods...
November 19, 2016: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27873219/immortalization-of-primary-microglia-a-new-platform-to-study-hiv-regulation-in-the-central-nervous-system
#19
Yoelvis Garcia-Mesa, Taylor R Jay, Mary Ann Checkley, Benjamin Luttge, Curtis Dobrowolski, Saba Valadkhan, Gary E Landreth, Jonathan Karn, David Alvarez-Carbonell
The major reservoirs for HIV in the CNS are in the microglia, perivascular macrophages, and to a lesser extent, astrocytes. To study the molecular events controlling HIV expression in the microglia, we developed a reliable and robust method to immortalize microglial cells from primary glia from fresh CNS tissues and commercially available frozen glial cells. Primary human cells, including cells obtained from adult brain tissue, were transformed with lentiviral vectors expressing SV40 T antigen or a combination of SVR40 T antigen and hTERT...
November 21, 2016: Journal of Neurovirology
https://www.readbyqxmd.com/read/27871240/abo-antigen-and-secretor-statuses-are-not-associated-with-gut-microbiota-composition-in-1-500-twins
#20
Emily R Davenport, Julia K Goodrich, Jordana T Bell, Tim D Spector, Ruth E Ley, Andrew G Clark
BACKGROUND: Host genetics is one of several factors known to shape human gut microbiome composition, however, the physiological processes underlying the heritability are largely unknown. Inter-individual differences in host factors secreted into the gut lumen may lead to variation in microbiome composition. One such factor is the ABO antigen. This molecule is not only expressed on the surface of red blood cells, but is also secreted from mucosal surfaces in individuals containing an intact FUT2 gene (secretors)...
November 21, 2016: BMC Genomics
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