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https://www.readbyqxmd.com/read/29220876/pharmacokinetics-clot-strength-and-safety-of-a-new-fibrinogen-concentrate-randomized-comparison-with-active-control-in-congenital-fibrinogen-deficiency
#1
C Ross, S Rangarajan, M Karimi, G H Toogeh, S Apte, T Lissitchkov, S Acharya, M J Manco-Johnson, A Srivastava, B Brand, B Schwartz, S Knaub, F Peyvandi
BACKGROUND: Human fibrinogen concentrate (HFC) corrects fibrinogen deficiency in congenital a-/hypofibrinogenaemia. OBJECTIVES: To assess pharmacokinetics (PK), effects on thromboelastometry maximum clot firmness (MCF), and safety of a new double virus-inactivated/eliminated, highly purified HFC vs. active control. PATIENTS/METHODS: In this multinational, randomized, phase II, open-label, crossover study in 22 congenital afibrinogenaemia patients ≥12 years, 70 mg kg-1 of new HFC (FIBRYGA, Octapharma AG) or control (Haemocomplettan® P/RiaSTAP™ , CSL Behring GmbH) were administered, followed by crossover to the other concentrate...
December 8, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29220720/induction-of-thymic-stromal-lymphopoietin-by-a-steroid-alkaloid-derivative-in-mouse-keratinocytes
#2
Yan Weng, Natsumi Mizuno, Jiangxu Dong, Ryosuke Segawa, Takayuki Yonezawa, Byung Yoon Cha, Je-Tae Woo, Takahiro Moriya, Masahiro Hiratsuka, Noriyasu Hirasawa
Thymic stromal lymphopoietin (TSLP) plays critical roles in inducing and exacerbating allergic diseases. Chemical compounds that induce TSLP production can enhance sensitization to antigens and exacerbate allergic inflammation. Hence, identifying such chemicals will be important to prevent an increase in allergic diseases. In the present study, we found, for the first time, that a steroid alkaloid derivative, code no. 02F04, concentration and time dependently induced mRNA expression and production of TSLP in a mouse keratinocyte cell line, PAM212...
December 5, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29220505/metabolic-characteristics-of-recently-diagnosed-adult-onset-autoimmune-diabetes-mellitus
#3
Oana P Zaharia, Pavel Bobrov, Klaus Strassburger, Kálmán Bódis, Yanislava Karusheva, Michaela Scholz, Daniel F Markgraf, Volker Burkart, Nanette C Schloot, Karsten Müssig, Julia Szendroedi, Michael Roden
Context and Objective: Among patients diagnosed with type 2 diabetes, autoimmune diabetes often remains undetected. Metabolic features of these patients are insufficiently characterized at present. Design, Setting and Patients: This study compared age- and sex-matched adult (41-62 years) humans with recent-onset diabetes: patients positive for antibodies against glutamic acid decarboxylase (GAD) and/or cytoplasmic islet-cell antigen with an insulin-free period of >6 months (ab+/ins-; previously termed latent autoimmune diabetes of adults, LADA), type 1 (ab+/ins+), type 2 diabetes (ab-/ins-) and glucose-tolerant humans (controls) of the German Diabetes Study (n=41/group)...
December 6, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29217660/chimeric-pneumoviridae-fusion-proteins-as-immunogens-to-induce-cross-neutralizing-antibody-responses
#4
Eduardo Olmedillas, Olga Cano, Isidoro Martínez, Daniel Luque, María C Terrón, Jason S McLellan, José A Melero, Vicente Más
Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV), two members of the Pneumoviridae family, account for the majority of severe lower respiratory tract infections worldwide in very young children. They are also a frequent cause of morbidity and mortality in the elderly and immunocompromised adults. High levels of neutralizing antibodies, mostly directed against the viral fusion (F) glycoprotein, correlate with protection against either hRSV or hMPV However, no cross-neutralization is observed in polyclonal antibody responses raised after virus infection or immunization with purified F proteins...
December 7, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29214036/strong-viral-associations-with-sle-among-filipinos
#5
Evan S Vista, Michael H Weisman, Mariko L Ishimori, Hua Chen, Rebecka L Bourn, Ben F Bruner, Laniyati Hamijoyo, Robelle D Tanangunan, Noga J Gal, Julie M Robertson, John B Harley, Joel M Guthridge, Sandra V Navarra, Judith A James
Objectives: Epstein-Barr virus (EBV) is considered an important environmental factor in SLE aetiology, but the relationship between SLE and EBV in the Filipino population is unknown. We tested associations between SLE, lupus-associated autoantibodies and seropositivity for EBV and other herpes viruses in the Filipino population. Methods: Sera from Filipino patients with SLE (n=233), unaffected first-degree relatives (FDRs, n=543) and unrelated controls (n=221) were tested for antibodies against EBV, cytomegalovirus (CMV) and herpes simplex viruses (HSV-1 and HSV-2) by standardised ELISAs...
2017: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29213258/the-complexity-of-antibody-responses-elicited-against-the-respiratory-syncytial-virus-glycoproteins-in-hospitalized-children-younger-than-2-years
#6
Alfonsina Trento, Rosa Rodríguez-Fernández, María I González-Sánchez, Felipe González-Martínez, Vicente Mas, Mónica Vázquez, Concepción Palomo, José A Melero
The influence of age and maternal antibodies on the antibody responses to human respiratory syncytial virus (hRSV) glycoproteins in very young children has been a matter of controversy. Both, immaturity of the immune system at very early age and suppression of the host immune response by high level of maternal antibodies have been claimed to limit the host antibody response to virus infection and to jeopardize the use of hRSV vaccines under development in that age group. Hence, the antibody responses to the two major hRSV glycoproteins (F and G) were evaluated in children younger than 2 years, hospitalized with laboratory confirmed hRSV bronchiolitis...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29213082/features-of-electronic-and-lattice-mechanisms-of-transboundary-heat-transfer-in-multilayer-nanolaminate-tialn-ag-coatings
#7
A I Kovalev, D L Wainstein, V O Vakhrushev, R Gago, F Soldera, J L Endrino, G S Fox-Rabinovich, S Veldhuis
Plasmon resonance heterogeneities were identified and studied along Ag and TiAlN layers within a multilayer stack in nanolaminate TiAlN/Ag coatings. For this purpose, a high-resolution plasmon microscopy was used. The plasmons intensity, energy, and depth of interface plasmon-polariton penetration were studied by scanning reflected electron energy loss spectroscopy. The heat conductivity of such metal-insulator-metal (MIM) nanolaminate coatings was measured by laser reflectometry. Dependencies of thermal conductivity coefficient of coatings, MIM interfaces, and resistivity of Ag layers as a function of the Ag-TiAlN bilayer thickness were calculated on the basis of experimental data...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29212956/icam1-neutrophils-promote-chronic-inflammation-via-asprv1-in-b-cell-dependent-autoimmune-encephalomyelitis
#8
Ryder F Whittaker Hawkins, Alexandre Patenaude, Aline Dumas, Rajiv Jain, Yodit Tesfagiorgis, Steven Kerfoot, Takeshi Matsui, Matthias Gunzer, Patrice E Poubelle, Catherine Larochelle, Martin Pelletier, Luc Vallières
Neutrophils contribute to demyelinating autoimmune diseases, yet their phenotype and functions have been elusive to date. Here, we demonstrate that ICAM1 surface expression distinguishes extra- from intravascular neutrophils in the mouse CNS during experimental autoimmune encephalomyelitis (EAE). Transcriptomic analysis of these 2 subpopulations indicated that neutrophils, once extravasated, acquire macrophage-like properties, including the potential for immunostimulation and MHC class II-mediated antigen presentation...
December 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/29212954/inhibition-of-akt-signaling-uncouples-t-cell-differentiation-from-expansion-for-receptor-engineered-adoptive-immunotherapy
#9
Christopher A Klebanoff, Joseph G Crompton, Anthony J Leonardi, Tori N Yamamoto, Smita S Chandran, Robert L Eil, Madhusudhanan Sukumar, Suman K Vodnala, Jinhui Hu, Yun Ji, David Clever, Mary A Black, Devikala Gurusamy, Michael J Kruhlak, Ping Jin, David F Stroncek, Luca Gattinoni, Steven A Feldman, Nicholas P Restifo
Adoptive immunotherapies using T cells genetically redirected with a chimeric antigen receptor (CAR) or T cell receptor (TCR) are entering mainstream clinical practice. Despite encouraging results, some patients do not respond to current therapies. In part, this phenomenon has been associated with infusion of reduced numbers of early memory T cells. Herein, we report that AKT signaling inhibition is compatible with CAR and TCR retroviral transduction of human T cells while promoting a CD62L-expressing central memory phenotype...
December 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/29211316/the-efficacy-of-prostate-specific-antigen-screening-impact-of-key-components-in-the-erspc-and-plco-trials
#10
Harry J de Koning, Roman Gulati, Sue M Moss, Jonas Hugosson, Paul F Pinsky, Christine D Berg, Anssi Auvinen, Gerald L Andriole, Monique J Roobol, E David Crawford, Vera Nelen, Maciej Kwiatkowski, Marco Zappa, Marcos Luján, Arnauld Villers, Tiago M de Carvalho, Eric J Feuer, Alex Tsodikov, Angela B Mariotto, Eveline A M Heijnsdijk, Ruth Etzioni
BACKGROUND: The European Randomized Study of Screening for Prostate Cancer (ERSPC) demonstrated that prostate-specific antigen (PSA) screening significantly reduced prostate cancer mortality (rate ratio, 0.79; 95% confidence interval, 0.69-0.91). The US Prostate, Lung, Colorectal, and Ovarian (PLCO) trial indicated no such reduction but had a wide 95% CI (rate ratio for prostate cancer mortality, 1.09; 95% CI, 0.87-1.36). Standard meta-analyses are unable to account for key differences between the trials that can impact the estimated effects of screening and the trials' point estimates...
December 6, 2017: Cancer
https://www.readbyqxmd.com/read/29211118/venous-blood-derivatives-as-fbs-substitutes-for-mesenchymal-stem-cells-a-systematic-scoping-review
#11
Luiz A Chisini, Marcus C M Conde, Guillermo Grazioli, Alissa S San Martin, Rodrigo Varella de Carvalho, Jacques E Nör, Flávio F Demarco
Although the biological properties of mesenchymal stem cells (MSC) are well-characterized in vitro, MSC clinical application is still far away to be achieved, mainly due to the need of xenogeneic substances for cell expansion, such as fetal bovine serum (FBS). FBS presents risks regarding pathogens transmissions and internalization of animal's proteins, which can unleash antigenic responses in patients after MSC implantation. A wide range of venous blood derivatives (VBD) has been reported as FBS substitutes showing promising results...
November 2017: Brazilian Dental Journal
https://www.readbyqxmd.com/read/29209570/car-t-cell-immunotherapy-of-met-expressing-malignant-mesothelioma
#12
Thivyan Thayaparan, Roseanna M Petrovic, Daniela Y Achkova, Tomasz Zabinski, David M Davies, Astero Klampatsa, Ana C Parente-Pereira, Lynsey M Whilding, Sjoukje Jc van der Stegen, Natalie Woodman, Michael Sheaff, Jennifer R Cochran, James F Spicer, John Maher
Mesothelioma is an incurable cancer for which effective therapies are required. Aberrant MET expression is prevalent in mesothelioma, although targeting using small molecule-based therapeutics has proven disappointing. Chimeric antigen receptors (CARs) couple the HLA-independent binding of a cell surface target to the delivery of a tailored T-cell activating signal. Here, we evaluated the anti-tumor activity of MET re-targeted CAR T-cells against mesothelioma. Using immunohistochemistry, MET was detected in 67% of malignant pleural mesotheliomas, most frequently of epithelioid or biphasic subtype...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29204701/combination-of-mab-ar20-5-anti-pd-l1-and-polyiclc-inhibits-tumor-progression-and-prolongs-survival-of-muc1-tg-mice-challenged-with-pancreatic-tumors
#13
Kamiya Mehla, Jarrod Tremayne, James A Grunkemeyer, Kelly A O'Connell, Maria M Steele, Thomas C Caffrey, Xinyi Zhu, Fang Yu, Pankaj K Singh, Birgit C Schultes, Ragupathy Madiyalakan, Christopher F Nicodemus, Michael A Hollingsworth
A substantial body of evidence suggests the existence of MUC1-specific antibodies and cytotoxic T cell activities in pancreatic cancer patients. However, tumor-induced immunosuppression renders these responses ineffective. The current study explores a novel therapeutic combination wherein tumor-bearing hosts can be immunologically primed with their own antigen, through opsonization with a tumor antigen-targeted antibody, mAb-AR20.5. We evaluated the efficacy of immunization with this antibody in combination with PolyICLC and anti-PD-L1...
December 4, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29203952/effect-of-intra-tumoral-magnetic-nanoparticle-hyperthermia-and-viral-nanoparticle-immunogenicity-on-primary-and-metastatic-cancer
#14
P Jack Hoopes, Courtney M Mazur, Bjorn Osterberg, Ailin Song, David J Gladstone, Nicole F Steinmetz, Frank A Veliz, Alicea A Bursey, Robert J Wagner, Steven N Fiering
Although there is long association of medical hyperthermia and immune stimulation, the relative lack of a quantifiable and reproducible effect has limited the utility and advancement of this relationship in preclinical/clinical cancer and non-cancer settings. Recent cancer-based immune findings (immune checkpoint modulators etc.) including improved mechanistic understanding and biological tools now make it possible to modify and exploit the immune system to benefit conventional cancer treatments such as radiation and hyperthermia...
January 2017: Proceedings of SPIE
https://www.readbyqxmd.com/read/29203544/mapping-protective-regions-on-a-three-dimensional-model-of-the-moraxella-catarrhalis-vaccine-antigen-oligopeptide-permease-a
#15
Antonia C Perez, Antoinette Johnson, Ziqiang Chen, Gregory E Wilding, Michael G Malkowski, Timothy F Murphy
A vaccine against Moraxella catarrhalis will reduce tremendous morbidity, mortality, and financial burden by preventing otitis media in children and exacerbations of COPD in adults. Oligopeptide permease A (OppA) is a candidate vaccine antigen that is 1) a nutritional virulence factor expressed on the bacterial cell surface during infection, 2) widely conserved among strains, 3) highly immunogenic, and 4) a protective antigen based on its capacity to induce protective responses in immunized animals. In the present study, we show that the antibodies to OppA following vaccination mediate accelerated clearance in animals following pulmonary challenge...
December 4, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29203539/novel-and-shared-neoantigen-derived-from-histone-3-variant-h3-3k27m-mutation-for-glioma-t-cell-therapy
#16
Zinal S Chheda, Gary Kohanbash, Kaori Okada, Naznin Jahan, John Sidney, Matteo Pecoraro, Xinbo Yang, Diego A Carrera, Kira M Downey, Shruti Shrivastav, Shuming Liu, Yi Lin, Chetana Lagisetti, Pavlina Chuntova, Payal B Watchmaker, Sabine Mueller, Ian F Pollack, Raja Rajalingam, Angel M Carcaboso, Matthias Mann, Alessandro Sette, K Christopher Garcia, Yafei Hou, Hideho Okada
The median overall survival for children with diffuse intrinsic pontine glioma (DIPG) is less than one year. The majority of diffuse midline gliomas, including more than 70% of DIPGs, harbor an amino acid substitution from lysine (K) to methionine (M) at position 27 of histone 3 variant 3 (H3.3). From a CD8+ T cell clone established by stimulation of HLA-A2+ CD8+ T cells with synthetic peptide encompassing the H3.3K27M mutation, complementary DNA for T cell receptor (TCR) α- and β-chains were cloned into a retroviral vector...
December 4, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29202119/enrichment-of-retroviral-sequences-in-brain-tissue-from-patients-with-severe-demyelinating-diseases
#17
J D Kriesel, P J Bhetariya, B K Chan, T Wilson, K F Fischer
Background: Our group has used deep sequencing to identify viral RNA signatures in human brain specimens. We have previously used this method to detect HSV1, GBV-C, and measles virus sequence in brain tissue from deceased donors. Deep sequencing was performed on brain specimens from a cohort of patients who died with progressive forms of MS, revealing evidence of increased expression of some human endogenous retrovirus (HERV) domains. Objectives: Identify RNA sequences and new antigens involved in the pathogenesis of MS...
August 2017: Journal of Emerging Diseases and Virology
https://www.readbyqxmd.com/read/29201030/toll-like-receptor-4-but-not-neutrophil-extracellular-traps-promote-ifn-type-i-expression-to-enhance-th2-responses-to-nippostrongylus-brasiliensis
#18
Christophe Pellefigues, Shiau-Choot Tang, Alfonso Schmidt, Ruby F White, Olivier Lamiable, Lisa M Connor, Christiane Ruedl, Jurek Dobrucki, Graham Le Gros, Franca Ronchese
The induction of Th2 responses is thought to be multifactorial, and emerge from specific pathways distinct from those associated with antagonistic antibacterial or antiviral Th1 responses. Here, we show that the recognition of non-viable Nippostrongylus brasiliensis (Nb) in the skin induces a strong recruitment of monocytes and neutrophils and the release of neutrophil extracellular traps (NETs). Nb also activates toll-like receptor 4 (TLR4) signaling with expression of Ifnb transcripts in the skin and the development of an IFN type I signature on helminth antigen-bearing dendritic cells in draining lymph nodes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29200193/immunogenetic-factors-driving-formation-of-ultralong-vh-cdr3-in-bos-taurus-antibodies
#19
Thaddeus C Deiss, Melissa Vadnais, Feng Wang, Patricia L Chen, Ali Torkamani, Waithaka Mwangi, Marie-Paule Lefranc, Michael F Criscitiello, Vaughn V Smider
The antibody repertoire of Bos taurus is characterized by a subset of variable heavy (VH) chain regions with ultralong third complementarity determining regions (CDR3) which, compared to other species, can provide a potent response to challenging antigens like HIV env. These unusual CDR3 can range to over seventy highly diverse amino acids in length and form unique β-ribbon 'stalk' and disulfide bonded 'knob' structures, far from the typical antigen binding site. The genetic components and processes for forming these unusual cattle antibody VH CDR3 are not well understood...
December 4, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29199372/comparative-assessment-of-recombinant-and-native-immunogenic-forms-of-fasciola-hepatica-proteins-for-serodiagnosis-of-sheep-fasciolosis
#20
Kobra Mokhtarian, Ahmad Reza Meamar, Majid Khoshmirsafa, Elham Razmjou, Leila Masoori, Majid Khanmohammadi, Lame Akhlaghi, Reza Falak
Laboratory diagnosis of sheep fasciolosis is commonly performed by coprological examinations; however, this method may lead to false negative results during the acute phase of the infection. Furthermore, the poor sensitivity of coprological methods is considered to be a paradox in the chronic phase of the infection. In this study, we compared the immunoreactivity of native and recombinant forms of Fasciola hepatica excretory/secretory antigens and determined their capabilities for the development of F. hepatica-specific immunoassays...
December 4, 2017: Parasitology Research
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