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https://www.readbyqxmd.com/read/28337956/acute-renal-graft-versus-host-disease-in-a-murine-model-of-allogeneic-bone-marrow-transplantation
#1
Peter M Schmid, Abdellatif Bouazzaoui, Karin Schmid, Christoph Birner, Christian Schach, Lars S Maier, Ernst Holler, Dierk H Endemann
Acute kidney injury (AKI) is a very common complication after allogeneic bone marrow transplantation (BMT) and associated with poor prognosis. Generally kidneys are assumed to be no direct target of Graft-versus-Host Disease (GvHD), and renal impairment is often attributed to several other factors occurring in the early phase after BMT. Our study aimed to prove the existence of renal GvHD in a fully MHC-mismatched model of BALB/c mice conditioned and transplanted according to two different intensity protocols...
March 23, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28317149/association-between-variants-in-genes-involved-in-the-immune-response-and-prostate-cancer-risk-in-men-randomized-to-the-finasteride-arm-in-the-prostate-cancer-prevention-trial
#2
Danyelle A Winchester, Cathee Till, Phyllis J Goodman, Catherine M Tangen, Regina M Santella, Teresa L Johnson-Pais, Robin J Leach, Jianfeng Xu, S Lilly Zheng, Ian M Thompson, M Scott Lucia, Scott M Lippman, Howard L Parnes, William B Isaacs, Angelo M De Marzo, Charles G Drake, Elizabeth A Platz
BACKGROUND: We reported that some, but not all single nucleotide polymorphisms (SNPs) in select immune response genes are associated with prostate cancer, but not individually with the prevalence of intraprostatic inflammation in the Prostate Cancer Prevention Trial (PCPT) placebo arm. Here, we investigated whether these same SNPs are associated with risk of lower- and higher-grade prostate cancer in men randomized to finasteride, and with prevalence of intraprostatic inflammation among controls...
March 20, 2017: Prostate
https://www.readbyqxmd.com/read/28280693/risk-factors-and-outcomes-of-delayed-graft-function-in-renal-transplant-recipients-receiving-a-steroid-sparing-immunosuppression-protocol
#3
Michelle Willicombe, Anna Rizzello, Dawn Goodall, Vassilios Papalois, Adam G McLean, David Taube
AIM: To analyse the risk factors and outcomes of delayed graft function (DGF) in patients receiving a steroid sparing protocol. METHODS: Four hundred and twenty-seven recipients of deceased donor kidney transplants were studied of which 135 (31.6%) experienced DGF. All patients received monoclonal antibody induction with a tacrolimus based, steroid sparing immunosuppression protocol. RESULTS: Five year patient survival was 87.2% and 94.9% in the DGF and primary graft function (PGF) group respectively, P = 0...
February 24, 2017: World Journal of Transplantation
https://www.readbyqxmd.com/read/28259042/probiotic-treatment-reduces-depressive-like-behaviour-in-rats-independently-of-diet
#4
Anders Abildgaard, Betina Elfving, Marianne Hokland, Gregers Wegener, Sten Lund
The gut microbiota has recently emerged as an important regulator of brain physiology and behaviour in animals, and ingestion of certain bacteria (probiotics) therefore appear to be a potential treatment for major depressive disorder (MDD). However, some conceptual and mechanistical aspects need further elucidation. We therefore aimed at investigating whether the habitual diet may interact with the effect of probiotics on depression-related behaviour and further examined some potentially involved mechanisms underlying the microbe-mediated behavioural effects...
February 16, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28222797/melanoma-antigen-specific-effector-t-cell-cytokine-secretion-patterns-in-patients-treated-with-ipilimumab
#5
Yana G Najjar, Fei Ding, Yan Lin, Robert VanderWeele, Lisa H Butterfield, Ahmad A Tarhini
BACKGROUND: In a previously reported study, patients with regionally advanced melanoma were treated with neoadjuvant ipilimumab (ipi) (Tarhini in PLoS ONE 9(2): e87705, 3). Significant changes in circulating myeloid derived suppressor cells (MDSC), regulatory T cells (Treg) and peptide specific type I CD4(+) and CD8(+) T cells were noted at week 6 that correlated with clinical outcome. Characterization of antigen-specific effector T cell secreted cytokines may shed insights into ipi associated T cell activation and function...
February 21, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28209780/microtubule-associated-protein-4-map4-controls-nanovesicle-dynamics-and-t-cell-activation
#6
Eugenio Bustos-Morán, Noelia Blas-Rus, Noa Martin-Cófreces, Francisco Sánchez-Madrid
The Immune Synapse (IS) is a specialized structure formed at the contact area between T lymphocytes and antigen-presenting cells (APC), essential for the adaptive immune response. Proper T cell activation requires its polarization towards the APC, which is highly dependent on the tubulin cytoskeleton. Microtubule associated protein-4 (MAP4) is a microtubule (MT)-stabilizing protein that controls MTs in physiological processes such as cell division, migration, vesicular transport or primary cilia formation. In this study, we have assessed the role of MAP4 in T cell activation...
February 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28202754/jak-stat-signaling-pathways-and-inhibitors-affect-reversion-of-envelope-mutated-hiv-1
#7
Yudong Quan, Hongtao Xu, Yingshan Han, Thibault Mesplède, Mark A Wainberg
HIV can spread by both cell-free and cell-to-cell transmission. Here, we show that numerous of the amino acid changes in Env that are close to the CD4 binding pocket can affect HIV replication. We generated a number of mutant viruses that were unable to infect T cells as cell-free viruses but were nevertheless able to infect certain T cell lines as cell-associated viruses, followed by reversion to wild type. However, the activation of JAK-STAT signaling pathways caused inhibition of such cell-to-cell infection as well as the reversion of multiple HIV Env mutants that displayed differences in ability to bind to the CD4 receptor...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28193233/tacrolimus-in-the-prevention-of-adverse-pregnancy-outcomes-and-diabetes-associated-embryopathies-in-obese-and-diabetic-mice
#8
Ahmad J H Albaghdadi, Melanie A Hewitt, Samantha M Putos, Michael Wells, Terence R S Ozolinš, Frederick W K Kan
BACKGROUND: T2DM is a high-risk pregnancy with adverse fetal and maternal outcomes including repeated miscarriages and fetal malformations. Despite the established association between placental insufficiency and poor maternal Th1-adaptability to the development of pregnancy complications in T2DM, there have been no established data to assess benefits of pre-pregnancy immunosuppression relative to gestational outcomes in T2DM. We hypothesized that pre-pregnancy macrolide immune suppression can re-establish normal placental development and uterine vascular adaptation in a mouse model of obesity-associated T2DM...
February 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28174320/isolation-of-luteal-endothelial-cells-and-functional-interactions-with-t-lymphocytes
#9
Sadhat S Walusimbi, Lindy Wetzel, David Townson, Joy Pate
The objectives of this study were to optimize the isolation of luteal endothelial cells (LEC) and examine their functional interactions with autologous T lymphocytes. Analysis by flow cytometry showed that the purity of LEC isolated by filtration was nearly 90% as indicated by Bandeiraea simplicifolia (BS)-1 lectin binding. LEC expressed mRNA for progesterone receptor (PGR), prostaglandin receptors (PTGFR, PTGER2 and 4, and PTGIR), tumor necrosis factor receptors (TNFRSF1A&B) and interleukin (IL) 1B receptors (IL1R1&2)...
February 7, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28145159/non-hla-gene-polymorphisms-in-juvenile-idiopathic-arthritis-associations-with-disease-outcome
#10
M Alberdi-Saugstrup, C Enevold, M Zak, S Nielsen, E Nordal, L Berntson, A Fasth, M Rygg, K Müller
OBJECTIVE: To test the hypothesis that non-HLA single-nucleotide polymorphisms (SNPs) associated with the risk of juvenile idiopathic arthritis (JIA) are risk factors for an unfavourable disease outcome at long-term follow-up. METHODS: The Nordic JIA cohort is a prospective multicentre study cohort of patients from the Nordic countries. In all, 193 patients met the inclusion criteria of having an 8 year follow-up assessment and available DNA sample. Seventeen SNPs met the inclusion criteria of having significant associations with JIA in at least two previous independent study cohorts...
February 1, 2017: Scandinavian Journal of Rheumatology
https://www.readbyqxmd.com/read/28130496/induction-of-il21-in-peripheral-t-follicular-helper-cells-is-an-indicator-of-influenza-vaccine-response-in-a-previously-vaccinated-hiv-infected-pediatric-cohort
#11
Lesley R de Armas, Nicola Cotugno, Suresh Pallikkuth, Li Pan, Stefano Rinaldi, M Celeste Sanchez, Louis Gonzalez, Alberto Cagigi, Paolo Rossi, Paolo Palma, Savita Pahwa
HIV-infected patients of all ages frequently underperform in response to seasonal influenza vaccination, despite virologic control of HIV. The molecular mechanisms governing this impairment, as well as predictive biomarkers for responsiveness, remain unknown. This study was performed in samples obtained prevaccination (T0) from HIV-infected children who received the 2012-2013 seasonal influenza vaccine. Response status was determined based on established criterion for hemagglutination inhibition titer; participants with a hemagglutination titer ≥1:40 plus a ≥4-fold increase over T0 at 3 wk postvaccination were designated as responders...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28127976/galantamine-has-impact-on-immunity-in-mice-exposed-to-keyhole-limpet-hemocyanin
#12
M Pohanka, J Zakova, J Fusek
OBJECTIVES: In this work, we hypothesized whether galantamine could interact with the cholinergic anti-inflammatory pathway and modulate immunity this way. BACKGROUND: Galantamine is a drug used for the therapy of Alzheimer disease. The drug inhibits enzyme acetylcholinesterase in the central nervous system, which causes better availability of neurotransmitter acetylcholine. METHODS: In the experiment, we immunized BALB/c laboratory mice by keyhole limpet hemocyanin (KLH) in combination with galantamine in a dose 0...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28116088/radiotherapy-and-mva-muc1-il-2-vaccine-act-synergistically-for-inducing-specific-immunity-to-muc-1-tumor-antigen
#13
Gilda G Hillman, Lyndsey A Reich, Shoshana E Rothstein, Lisa M Abernathy, Matthew D Fountain, Kali Hankerd, Christopher K Yunker, Joseph T Rakowski, Eric Quemeneur, Philippe Slos
BACKGROUND: We previously demonstrated that tumor irradiation potentiates cancer vaccines using genetic modification of tumor cells in murine tumor models. To investigate whether tumor irradiation augments the immune response to MUC1 tumor antigen, we have tested the efficacy of tumor irradiation combined with an MVA-MUC1-IL2 cancer vaccine (Transgene TG4010) for murine renal adenocarcinoma (Renca) cells transfected with MUC1. METHODS: Established subcutaneous Renca-MUC1 tumors were treated with 8 Gy radiation on day 11 and peritumoral injections of MVA-MUC1-IL2 vector on day 12 and 17, or using a reverse sequence of vaccine followed by radiation...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28089909/immunosuppression-via-loss-of-il2r%C3%AE-enhances-long-term-functional-integration-of-hesc-derived-photoreceptors-in-the-mouse-retina
#14
Jie Zhu, Helen Cifuentes, Joseph Reynolds, Deepak A Lamba
Loss of photoreceptors is a common endpoint in degenerative retinal diseases. Human pluripotent stem cells provide a potential source for photoreceptor replacement, but, even in mouse models, the efficiency and efficacy of transplantation-based repair remains poor. In this study, we examined the degree to which immune rejection contributes to these disappointing outcomes using an immunodeficient IL2 receptor γ (IL2rγ)-null mouse model. Our results show that prevention of cell rejection in the normal and degenerating retinal environment significantly improves long-term survival and integration of hESC-derived donor retinal cells...
December 29, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/28076753/cd25-targeted-therapy-of-chemotherapy-resistant-leukemic-stem-cells-using-dr5-specific-trail-peptide
#15
Jayaprakasam Madhumathi, Surapally Sridevi, Rama Shanker Verma
Chemotherapy resistant leukemic stem cells (LSCs) are being targeted as a modern therapeutic approach to prevent disease relapse. LSCs isolated from methotrexate resistant side population (SP) of leukemic cell lines HL60 and MOLT4 exhibited high levels of CD25 and TRAIL R2/DR5 which are potential targets. Recombinant immunotoxin conjugating IL2α with TRAIL peptide mimetic was constructed for DR5 receptor specific targeting of LSCs and were tested in total cell population and LSCs. IL2-TRAIL peptide induced apoptosis in drug resistant SP cells from cell lines and showed potent cytotoxicity in PBMCs derived from leukemic patients with an efficacy of 81...
January 4, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28056941/neutrophil-lymphocyte-ratio-as-a-predictive-biomarker-for-response-to-high-dose-interleukin-2-in-patients-with-renal-cell-carcinoma
#16
James A Kuzman, David D Stenehjem, Joseph Merriman, Archana M Agarwal, Shiven B Patel, Andrew W Hahn, Anitha Alex, Dan Albertson, David M Gill, Neeraj Agarwal
BACKGROUND: Immunotherapy with high-dose interleukin-2 (HD-IL2) results in long-term survival in some metastatic renal cell carcinoma (mRCC) patients but has significant acute toxicities. Biomarkers predicting response to therapy are needed to better select patients most likely to benefit. NLR (absolute neutrophil count (ANC)/absolute lymphocyte count (ALC)) is a prognostic and predicative biomarker in various malignancies. The goal was to determine whether NLR can predict response to HD-IL2 in this setting...
January 5, 2017: BMC Urology
https://www.readbyqxmd.com/read/27999747/immune-response-and-long-term-clinical-outcome-in-advanced-melanoma-patients-vaccinated-with-tumor-mrna-transfected-dendritic-cells
#17
Jon Amund Kyte, Steinar Aamdal, Svein Dueland, Stein Sæbøe-Larsen, Else Marit Inderberg, Ulf Erik Madsbu, Eva Skovlund, Gustav Gaudernack, Gunnar Kvalheim
The most effective anticancer immune responses are probably directed against patient-specific neoantigens. We have developed a melanoma vaccine targeting this individual mutanome based on dendritic cells (DCs) loaded with autologous tumor-mRNA. Here, we report a phase I/II trial evaluating toxicity, immune response and clinical outcome in 31 metastatic melanoma patients. The first cohort (n = 22) received the vaccine without any adjuvant; the next cohort (n = 9) received adjuvant IL2. Each subject received four weekly intranodal or intradermal injections, followed by optional monthly vaccines...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27992487/changes-in-host-cytokine-patterns-of-tb-patients-with-different-bacterial-loads-detected-using-16s-rrna-analysis
#18
Rhiannon Heslop, Adama L Bojang, Sheikh Jarju, Joseph Mendy, Sarah Mulwa, Ousman Secka, Francis S Mendy, Olumuyiwa Owolabi, Beate Kampmann, Jayne S Sutherland
BACKGROUND: Tuberculosis (TB) has overtaken HIV as the biggest infectious disease killer, with the majority of deaths occurring in sub-Saharan Africa. However it is unknown how differences in bacterial load alter host immune profiles in the sputum and blood of TB patients. METHODS: 16S ribosomal RNA analysis was used to determine bacterial load in sputum samples obtained from 173 patients with active TB (57 pre-treatment and 116 post-treatment). Host analyte concentrations in sputum and Mycobacterium tuberculosis (Mtb) antigen stimulated whole blood assay supernatants were analysed using multiplex cytokine arrays...
2016: PloS One
https://www.readbyqxmd.com/read/27989104/dna-demethylation-of-the-foxp3-enhancer-is-maintained-through-modulation-of-ten-eleven-translocation-and-dna-methyltransferases
#19
Varun Sasidharan Nair, Mi Hye Song, Myunggon Ko, Kwon Ik Oh
Stable expression of Foxp3 is ensured by demethylation of CpG motifs in the Foxp3 intronic element, the conserved non-coding sequence 2 (CNS2), which persists throughout the lifespan of regulatory T cells (Tregs). However, little is known about the mechanisms on how CNS2 demethylation is sustained. In this study, we found that Ten-Eleven-Translocation (Tet) DNA dioxygenase protects the CpG motifs of CNS2 from re-methylation by DNA methyltransferases (Dnmts) and prevents Tregs from losing Foxp3 expression under inflammatory conditions...
December 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27986689/hla-b-57-and-ifnl4-related-polymorphisms-are-associated-with-protection-against-hiv-1-disease-progression-in-controllers
#20
B Dominguez-Molina, L Tarancon-Diez, S Hua, C Abad-Molina, E Rodriguez-Gallego, K Machmach, F Vidal, C Tural, S Moreno, J M Goñi, E Ramírez de Arellano, M Del Val, M F Gonzalez-Escribano, J Del Romero, C Rodriguez, L Capa, P Viciana, J Alcamí, X G Yu, B D Walker, Manuel Leal, M Lichterfeld, E Ruiz-Mateos
BACKGROUND: HIV-1-controllers maintain HIV-1 viremia at low levels (normally <2000 HIV-RNA copies/mL) without antiretroviral treatment. However, some HIV-1-controllers have evidence of immunologic progression with marked CD4(+)T-cell decline. We investigated host genetic factors associated with protection against CD4(+)T-cell loss in HIV-1-controllers. METHODS: We analysed the association of interferon lambda 4 (IFNL4)-related polymorphisms and HLA-B haplotypes within Long Term Non-Progressor HIV-1-controllers ((LTNP-C), defined by maintaining CD4(+)T-cells counts >500 cells/mm(3) for more than 7 years after HIV-1 diagnosis) versus non-LTNP-C, who developed CD4(+)T-cells counts <500 cells/mm(3) Both a Spanish study cohort (n=140) and an international validation cohort (n=914) were examined...
December 16, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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