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https://www.readbyqxmd.com/read/28097289/binding-of-cll-subset-4-b-cell-receptor-immunoglobulins-to-viable-human-memory-b-lymphocytes-requires-a-distinctive-igkv-somatic-mutation
#1
Rosa Catera, Yun Liu, Chao Gao, Xiao-Jie Yan, Amanda Magli, Steven L Allen, Jonathan E Kolitz, Kanti R Rai, Charles C Chu, Ten Feizi, Kostas Stamatopoulos, Nicholas Chiorazzi
Amino acid replacement mutations in certain CLL stereotyped B-cell receptor (BCR) immunoglobulins (IGs) at defined positions within antigen-binding sites strongly imply antigen selection. Prime examples of this are CLL subset 4 BCR IGs using IGHV4-34/IGHD5-18/IGHJ6 and IGKV2-30/IGKJ2 rearrangements. Conspicuously and unlike most CLL IGs, subset 4 IGs do not bind apoptotic cells. By testing the (auto)antigenic reactivities of subset 4 IGs toward viable lymphoid-lineage cells and specific autoantigens typically bound by IGHV4-34(+) IGs, we found IGs from both subset 4 and non-subset 4 IGHV4-34-expressing CLL cases bind naïve B cells...
January 12, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28096682/decreased-mir-503-expression-in-gastric-cancer-is-inversely-correlated-with-serum-carcinoembryonic-antigen-and-acts-as-a-potential-prognostic-and-diagnostic-biomarker
#2
Daoyi Wu, Gaojian Cao, Zhenfeng Huang, Kai Jin, Haowei Hu, Jie Yu, Yu Zeng
BACKGROUND: Altered expression of miR-503 has been linked to human carcinogenesis. In this present study, we aimed to detect the potential for miR-503 as a novel biomarker for gastric cancer (GC) patients. MATERIALS AND METHODS: The relative mRNA level of miR-503 in serum and tissue of 68 GC patients and serum of 32 healthy volunteers was determined by real-time reverse transcription quantitative polymerase chain reaction. RESULTS: The miR-503 level was significantly lower in the tissue and serum of GC than their counterparts (all P<0...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28096374/phylogenetic-analysis-of-the-human-antibody-repertoire-reveals-quantitative-signatures-of-immune-senescence-and-aging
#3
Charles F A de Bourcy, Cesar J Lopez Angel, Christopher Vollmers, Cornelia L Dekker, Mark M Davis, Stephen R Quake
The elderly have reduced humoral immunity, as manifested by increased susceptibility to infections and impaired vaccine responses. To investigate the effects of aging on B-cell receptor (BCR) repertoire evolution during an immunological challenge, we used a phylogenetic distance metric to analyze Ig heavy-chain transcript sequences in both young and elderly individuals before and after influenza vaccination. We determined that BCR repertoires become increasingly specialized over a span of decades, but less plastic...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28092864/augmentation-of-humoral-and-cellular-immunity-in-response-to-tetanus-and-diphtheria-toxoids-by-supercritical-carbon-dioxide-extracts-of-hippophae-rhamnoides-l-leaves
#4
Bindhya Jayashankar, Divya Singh, Himanshi Tanwar, K P Mishra, Swetha Murthy, Sudipta Chanda, Jigni Mishra, R Tulswani, K Misra, S B Singh, Lilly Ganju
Hippophae rhamnoides L. commonly known as Seabuckthorn (SBT), a wild shrub of family Elaegnacea, has extensively used for treating various ailments like skin diseases, jaundice, asthma, lung troubles. SBT leaves have been reported to possess several pharmacological properties including immunomodulatory, antioxidant, anti-inflammatory, antimicrobial and tissue regeneration etc. The present study was undertaken to evaluate the adjuvant property of supercritical carbon dioxide extracts (SCEs 300ET and 350ET) of SBT leaves in balb/c mice immunized with Tetanus and Diphtheria toxoids...
January 13, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28092370/api5-confers-cancer-stem-cell-like-properties-through-the-fgf2-nanog-axis
#5
K-H Song, H Cho, S Kim, H-J Lee, S J Oh, S R Woo, S-O Hong, H S Jang, K H Noh, C H Choi, J-Y Chung, S M Hewitt, J-H Kim, M Son, S-H Kim, B I Lee, H-C Park, Y-K Bae, T W Kim
Immune selection drives the evolution of tumor cells toward an immune-resistant and cancer stem cell (CSC)-like phenotype. We reported that apoptosis inhibitor-5 (API5) acts as an immune escape factor, which has a significant role in controlling immune resistance to antigen-specific T cells, but its functional association with CSC-like properties remains largely unknown. In this study, we demonstrated for the first time that API5 confers CSC-like properties, including NANOG expression, the frequency of CD44-positive cells and sphere-forming capacity...
January 16, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28092143/human-leucocyte-antigen-adverse-drug-reaction-associations-from-a-perspective-of-ethnicity
#6
REVIEW
G S Ghattaoraya, D Middleton, E J M Santos, R Dickson, A R Jones, A Alfirevic
Whilst immune-mediated adverse drug reactions (ADRs) are rare, they are potentially life-threatening and present a major problem for clinicians. The underlying mechanisms that cause ADRs are not fully understood although genomewide association studies (GWAS) and case-control investigations have associated human leucocyte antigen (HLA) alleles as risk factors. There is evidence that a patient's ethnic background can have an impact on their risk of developing an ADR. This review summarizes the evidence related to HLA alleles and ADRs with particular focus on patient ethnicity...
February 2017: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/28090318/dengue-virus-antibodies-enhance-zika-virus-infection
#7
Lauren M Paul, Eric R Carlin, Meagan M Jenkins, Amanda L Tan, Carolyn M Barcellona, Cindo O Nicholson, Scott F Michael, Sharon Isern
For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases. Recent reports of severe disease associated with ZIKV have greatly heightened awareness. It is anticipated that ZIKV will continue to spread in the Americas and globally where competent Aedes mosquito vectors are found. Dengue virus (DENV), the most common mosquito-transmitted human flavivirus, is both well-established and the source of outbreaks in areas of recent ZIKV introduction...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28086979/b-cell-repertoires-in-hla-sensitized-kidney-transplant-candidates-undergoing-desensitization-therapy
#8
John F Beausang, H Christina Fan, Rene Sit, Maria U Hutchins, Kshama Jirage, Rachael Curtis, Edward Hutchins, Stephen R Quake, Julie M Yabu
BACKGROUND: Kidney transplantation is the most effective treatment for end-stage renal disease. Sensitization refers to pre-existing antibodies against human leukocyte antigen (HLA) protein and remains a major barrier to successful transplantation. Despite implementation of desensitization strategies, many candidates fail to respond. Our objective was to determine whether measuring B cell repertoires could differentiate candidates that respond to desensitization therapy. METHODS: We developed an assay based on high-throughput DNA sequencing of the variable domain of the heavy chain of immunoglobulin genes to measure changes in B cell repertoires in 19 highly HLA-sensitized kidney transplant candidates undergoing desensitization and 7 controls with low to moderate HLA sensitization levels...
January 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28079473/protective-immunity-against-influenza-in-hla-a2-transgenic-mice-by-modified-vaccinia-virus-ankara-vectored-vaccines-containing-internal-influenza-proteins
#9
Giuseppina Di Mario, Ester Sciaraffia, Marzia Facchini, Francesco Gubinelli, Elisa Soprana, Maddalena Panigada, Valentina Bernasconi, Bruno Garulli, Antonio Siccardi, Isabella Donatelli, Maria R Castrucci
BACKGROUND: The emergence of novel strains of influenza A viruses with hemagglutinins (HAs) that are antigenically distinct from those circulating in humans, and thus have pandemic potential, pose concerns and call for the development of more broadly protective influenza vaccines. In the present study, modified vaccinia virus Ankara (MVA) encoding internal influenza antigens were evaluated for their immunogenicity and ability to protect HLA-A2.1 transgenic (AAD) mice from infection with influenza viruses...
January 12, 2017: Pathogens and Global Health
https://www.readbyqxmd.com/read/28077698/detection-of-antigenic-variants-of-swine-subtype-h3-influenza-a-viruses-from-clinical-samples
#10
Brigitte E Martin, Andrew S Bowman, Lei Li, Jacqueline M Nolting, David R Smith, Larry A Hanson, Xiu-Feng Wan
A large population of genetically and antigenically diverse influenza A viruses (IAVs) are circulating among the swine population, playing an important role in influenza ecology. Swine IAVs not only cause outbreaks among swine, but they can also be transmitted to humans, causing sporadic infections and even pandemic outbreaks. Antigenic characterization of swine IAVs are key to understanding the natural history of these viruses in swine and to selecting strains for effective vaccines. However, influenza outbreaks generally spread rapidly among swine, and the conventional methods for antigenic characterization require virus propagation, a time-consuming process that can significantly reduce the effectiveness of vaccination programs...
January 11, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28077675/post-hoc-assessment-of-the-immunogenicity-of-bioengineered-factor-viia-demonstrates-the-use-of-preclinical-tools
#11
Kasper Lamberth, Stine Louise Reedtz-Runge, Jonathan Simon, Ksenia Klementyeva, Gouri Shankar Pandey, Søren Berg Padkjær, Véronique Pascal, Ileana R León, Charlotte Nini Gudme, Søren Buus, Zuben E Sauna
Immunogenicity is an important consideration in the licensure of a therapeutic protein because the development of neutralizing anti-drug antibodies (ADAs) can affect both safety and efficacy. Neoantigens introduced by bioengineering of a protein drug are a particular cause for concern. The development of a bioengineered recombinant factor VIIa (rFVIIa) analog was discontinued after phase 3 trials because of the development of ADAs. The unmodified parent molecule (rFVIIa), on the other hand, has been successfully used as a drug for more than two decades with no reports of immunogenicity in congenital hemophilia patients with inhibitors...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28077654/neutralization-of-diverse-human-cytomegalovirus-strains-conferred-by-antibodies-targets-viral-gh-gl-pul128-131-pentameric-complex
#12
Sha Ha, Fengsheng Li, Matthew C Troutman, Daniel C Freed, Aimin Tang, John W Loughney, Dai Wang, I-Ming Wang, Josef Vlasak, David C Nickle, Richard R Rustandi, Melissa Hamm, Pete A DePhillips, Ningyan Zhang, Jason S McLellan, Hua Zhu, Stuart P Adler, Michael A McVoy, Zhiqiang An, Tong-Ming Fu
: Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection and developing a prophylactic vaccine is of high priority to public health. We recently reported a replication-defective human cytomegalovirus with restored pentameric complex gH/gL/pUL128-131 for prevention of congenital HCMV infection. While the quantity of vaccine-induced antibody responses can be measured in a viral neutralization assay, assessing the quality of such responses, including the ability of vaccine-induced antibodies to cross neutralize the field strains of HCMV, remains a challenge...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28065517/peritoneal-macrophage-heterogeneity-is-associated-with-different-peritoneal-dialysis-outcomes
#13
Chia-Te Liao, Robert Andrews, Leah E Wallace, Mohd Wajid A Khan, Ann Kift-Morgan, Nicholas Topley, Donald J Fraser, Philip R Taylor
Peritonitis remains the major obstacle for the maintenance of long-term peritoneal dialysis and dysregulated host peritoneal immune responses may compromise local anti-infectious defense, leading to treatment failure. Whilst, tissue mononuclear phagocytes, comprising macrophages and dendritic cells, are central to a host response to pathogens and the development of adaptive immune responses, they are poorly characterized in the human peritoneum. Combining flow cytometry with global transcriptome analysis, the phenotypic features and lineage identity of the major CD14(+) macrophage and CD1c(+) dendritic cell subsets in dialysis effluent were defined...
January 5, 2017: Kidney International
https://www.readbyqxmd.com/read/28064419/pharmacokinetics-and-pharmacogenetics-of-carbamazepine-in-children
#14
Natasa Djordjevic, Slobodan M Jankovic, Jasmina R Milovanovic
Although carbamazepine is one of the oldest anticonvulsant drugs, it is still heavily utilized for treatment of epilepsy in children. The aim of this article was to review the current knowledge about pharmacokinetics and pharmacogenetics of carbamazepine in children. The literature for this review was systematically searched for in the MEDLINE and SCINDEKS databases. Oral bioavailability of carbamazepine in children is about 75-85%, and it is approximately 75-85% bound to plasma proteins. Apparent volume of distribution is 1...
January 7, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28062405/presence-of-multiple-spondyloarthritis-spa-features-is-important-but-not-sufficient-for-a-diagnosis-of-axial-spondyloarthritis-data-from-the-spondyloarthritis-caught-early-space-cohort
#15
Z Ez-Zaitouni, P A C Bakker, M van Lunteren, I J Berg, R Landewé, M van Oosterhout, M Lorenzin, D van der Heijde, F A van Gaalen
OBJECTIVES: Concerns have been raised about overdiagnosis of axial spondyloarthritis (axSpA). We investigated whether patients with chronic back pain (CBP) of short duration and multiple SpA features are always diagnosed with axSpA by the rheumatologist, and to what extent fulfilment of the Assessment of SpondyloArthritis International Society (ASAS) axSpA criteria is associated with an axSpA diagnosis. METHODS: Baseline data from 500 patients from the SPondyloArthritis Caught Early cohort which includes patients with CBP (≥3 months, ≤2 years, onset <45 years) were analysed...
January 6, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28061386/characterization-of-the-disassembly-and-reassembly-of-the-hbv-glycoprotein-surface-antigen-a-pliable-nanoparticle-vaccine-platform
#16
John R Gallagher, Udana Torian, Dustin M McCraw, Audray K Harris
While nanoparticle vaccine technology is gaining interest due to the success of vaccines like those for the human papillomavirus that is based on viral capsid nanoparticles, little information is available on the disassembly and reassembly of viral surface glycoprotein-based nanoparticles. One such particle is the hepatitis B virus surface antigen (sAg) that exists as nanoparticles. Here we show, using biochemical analysis coupled with electron microscopy, that sAg nanoparticle disassembly requires both reducing agent to disrupt intermolecular disulfide bonds, and detergent to disrupt hydrophobic interactions that stabilize the nanoparticle...
January 3, 2017: Virology
https://www.readbyqxmd.com/read/28057906/analysis-of-porcine-rotavirus-a-enterotoxin-gene-for-structure-function-relationship
#17
Sharad Saurabh, Shubhankar Sircar, Jobin Jose Kattoor, Souvik Ghosh, N Kobayashi, Krisztian Banyai, O R Vinod Kumar, Ujjawal De, Nihar Ranjan Sahoo, Kuldeep Dhama, Yashpal Singh Malik
Rotavirus (RV) infected piglets are presumed to be the latent sources of heterologous RV infection to humans and other animals. In RVs, non-structural protein 4 (NSP4) is the major virulence factor with pleiotropic properties. In this study, we analyzed nsp4 gene from porcine RVs, isolated from diarrheic and non-diarrheic cases, at different levels of protein folding to explore any correlation with their diarrhea inducing capabilities and evolution of nsp4 in porcine population. The full length nsp4 genes were amplified, cloned, sequenced and analyzed for antigenic epitopes, RotaC classification, homology, genetic relationship, modeling of NSP4 protein and prediction for post translational modification...
January 4, 2017: Journal of Veterinary Science
https://www.readbyqxmd.com/read/28049560/a-recombinant-fusion-protein-displaying-murine-and-human-mhc-class-i-and-ii-specific-epitopes-protects-against-leishmania-amazonensis-infection
#18
Vívian T Martins, Daniela P Lage, Mariana C Duarte, Ana Maria R S Carvalho, Lourena E Costa, Tiago A O Mendes, Danniele L Vale, Daniel Menezes-Souza, Bruno M Roatt, Carlos A P Tavares, Manuel Soto, Eduardo A F Coelho
Tegumentary leishmaniasis (TL) constitutes a major public health problem with significant morbidity worldwide. Synthetic peptide-based vaccines are attractive candidates to protect against leishmaniasis, since T cell-specific epitopes can be delivery to antigen-presenting cells, leading to the generation of a Th1 cell-mediated immunity. In this context, the present study aims to evaluate the immunogenicity and protective efficacy of a vaccine composed of major histocompatibility complex class I and II-restricted epitopes derived from four Leishmania infantum proteins to protect mice against Leishmania amazonensis infection...
December 28, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/28045579/gut-microbiota-as-a-source-of-a-surrogate-antigen-that-triggers-autoimmunity-in-an-immune-privileged-site
#19
Carlos R Zárate-Bladés, Reiko Horai, Mary J Mattapallil, Nadim J Ajami, Matthew Wong, Joseph F Petrosino, Kikuji Itoh, Chi-Chao Chan, Rachel R Caspi
Recent discoveries on the role of commensal microbiota have significantly changed our understanding of human physiology. The host-microbiota interplay is now an important aspect to take into account to understand immune responses and immunological diseases. Autoimmune uveitis is a sight-threatening disease that arises without a known infectious etiology. It is unknown where and how autoreactive T cells become primed to trigger disease in the eye, which is an immune privileged site. We recently reported data supporting the notion that retina-specific T cells receive a signal in the gut from commensal microbiota-derived cross-reactive antigen(s) and trigger autoimmune uveitis in the R161H mouse model...
January 3, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28043905/association-of-liver-injury-from-specific-drugs-or-groups-of-drugs-with-polymorphisms-in-hla-and-other-genes-in-a-genome-wide-association-study
#20
Paola Nicoletti, Guruprasad P Aithal, Einar S Bjornsson, Raul J Andrade, Ashley Sawle, Marco Arrese, Huiman X Barnhart, Emmanuelle Bondon-Guitton, Paul H Hayashi, Fernando Bessone, Alfonso Carvajal, Ingolf Cascorbi, Elizabeth T Cirulli, Naga Chalasani, Anita Conforti, Sally A Coulthard, Mark J Daly, Christopher P Day, John F Dillon, Robert J Fontana, Jane I Grove, Pär Hallberg, Nelia Hernández, Luisa Ibáñez, Gerd A Kullak-Ublick, Tarja Laitinen, Dominique Larrey, M Isabel Lucena, Anke H Maitland-van der Zee, Jennifer H Martin, Mariam Molokhia, Munir Pirmohamed, Elizabeth E Powell, Shengying Qin, Jose Serrano, Camilla Stephens, Andrew Stolz, Mia Wadelius, Paul B Watkins, Aris Floratos, Yufeng Shen, Matthew R Nelson, Thomas J Urban, Ann K Daly
BACKGROUND & AIMS: We performed a genome-wide association study (GWAS) to identify genetic risk factors for drug-induced liver injury (DILI) from licensed drugs without previously reported genetic risk factors. METHODS: We performed a GWAS of 862 persons with DILI and 10588 population-matched controls. The first set of cases was recruited prior to May 2009 in Europe (n=137) or the USA (n=274). The second set of cases were identified from May 2009 through May 2013 from international collaborative studies performed in Europe, the USA and South America...
December 30, 2016: Gastroenterology
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