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https://www.readbyqxmd.com/read/29150880/a-slowly-developed-severe-cutaneous-adverse-reaction-to-idelalisib
#1
L Huilaja, O Lindgren, M Soronen, T Siitonen, K Tasanen
Intracellular signal mediator phosphatidylinositol-3-kinase (PIK3K) -δ, an isoform of PIK3K, is expressed in hematopoietic cells especially in lymphoid lineage 1. Idelalisib is a novel PIK3K-δ targeted kinase inhibitor which is approved for relapsed follicular B-cell non-Hodgkin lymphoma as a monotherapy and in combination with rituximab, an anti-CD20 antibody, for relapsed chronic lymphocytic leukemia (CLL) 2. Only one case describing the clinical features of severe cutaneous adverse reaction (SCAR) of idelalisib in detail has been previously published 3...
November 17, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29150843/liver-fibrosis-is-associated-with-cutaneous-inflammation-in-the-imiquimod-induced-murine-model-of-psoriasiform-dermatitis
#2
P Vasseur, M Pohin, J F Jégou, L Favot, N Venisse, J Mcheik, F Morel, J C Lecron, C Silvain
BACKGROUND: Psoriasis associates several extra-cutaneous manifestations. Little is known about hepatic parameters specifically associated with psoriasis. OBJECTIVE: To study whether psoriasiform dermatitis is associated with liver injury. METHODS: We studied liver parameters of inflammation and fibrosis in a murine model of psoriasiform dermatitis induced by topical application of imiquimod for nine weeks. RESULTS: Topical treatment with imiquimod induced a form of psoriasiform dermatitis reminiscent of the human disorder, characterized by thickened and scaly skin, psoriasiform epidermal hyperplasia, altered keratinocyte differentiation, and cutaneous overexpression of interleukin-17A...
November 18, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29150659/ectopic-foxp3-expression-preserves-primitive-features-of-human-hematopoietic-stem-cells-while-impairing-functional-t-cell-differentiation
#3
F R Santoni de Sio, L Passerini, M M Valente, F Russo, L Naldini, M G Roncarolo, R Bacchetta
FOXP3 is the transcription factor ruling regulatory T cell function and maintenance of peripheral immune tolerance, and mutations in its coding gene causes IPEX autoimmune syndrome. FOXP3 is also a cell-cycle inhibitor and onco-suppressor in different cell types. In this work, we investigate the effect of ectopic FOXP3 expression on HSC differentiation and we challenged this approach as a possible HSC-based gene therapy for IPEX. FOXP3-expressing HSC showed reduced proliferation ability and increased maintenance of primitive markers in vitro in both liquid and OP9-ΔL1 co-cultures...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150639/in-vitro-maturation-and-in-vivo-integration-and-function-of-an-engineered-cell-seeded-disc-like-angle-ply-structure-daps-for-total-disc-arthroplasty
#4
J T Martin, S E Gullbrand, D H Kim, K Ikuta, C G Pfeifer, B G Ashinsky, L J Smith, D M Elliott, H E Smith, R L Mauck
Total disc replacement with an engineered substitute is a promising avenue for treating advanced intervertebral disc disease. Toward this goal, we developed cell-seeded disc-like angle ply structures (DAPS) and showed through in vitro studies that these constructs mature to match native disc composition, structure, and function with long-term culture. We then evaluated DAPS performance in an in vivo rat model of total disc replacement; over 5 weeks in vivo, DAPS maintained their structure, prevented intervertebral bony fusion, and matched native disc mechanical function at physiologic loads in situ...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150567/amplifying-ifn-%C3%AE-signaling-in-dendritic-cells-by-cd11c-specific-loss-of-socs1-increases-innate-immunity-to-infection-while-decreasing-adaptive-immunity
#5
Alejandro F Alice, Gwen Kramer, Shelly Bambina, Jason R Baird, Keith S Bahjat, Michael J Gough, Marka R Crittenden
Although prophylactic vaccines provide protective humoral immunity against infectious agents, vaccines that elicit potent CD8 T cell responses are valuable tools to shape and drive cellular immunity against cancer and intracellular infection. In particular, IFN-γ-polarized cytotoxic CD8 T cell immunity is considered optimal for protective immunity against intracellular Ags. Suppressor of cytokine signaling (SOCS)1 is a cross-functional negative regulator of TLR and cytokine receptor signaling via degradation of the receptor-signaling complex...
November 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29150562/the-role-of-mhc-e-in-t-cell-immunity-is-conserved-among-humans-rhesus-macaques-and-cynomolgus-macaques
#6
Helen L Wu, Roger W Wiseman, Colette M Hughes, Gabriela M Webb, Shaheed A Abdulhaqq, Benjamin N Bimber, Katherine B Hammond, Jason S Reed, Lina Gao, Benjamin J Burwitz, Justin M Greene, Fidel Ferrer, Alfred W Legasse, Michael K Axthelm, Byung S Park, Simon Brackenridge, Nicholas J Maness, Andrew J McMichael, Louis J Picker, David H O'Connor, Scott G Hansen, Jonah B Sacha
MHC-E is a highly conserved nonclassical MHC class Ib molecule that predominantly binds and presents MHC class Ia leader sequence-derived peptides for NK cell regulation. However, MHC-E also binds pathogen-derived peptide Ags for presentation to CD8(+) T cells. Given this role in adaptive immunity and its highly monomorphic nature in the human population, HLA-E is an attractive target for novel vaccine and immunotherapeutic modalities. Development of HLA-E-targeted therapies will require a physiologically relevant animal model that recapitulates HLA-E-restricted T cell biology...
November 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29150407/disease-trends-over-time-and-cd4-ccr5-t-cells-expansion-predict-carotid-atherosclerosis-development-in-patients-with-systemic-lupus-erythematosus
#7
A Baragetti, G A Ramirez, M Magnoni, K Garlaschelli, L Grigore, M Berteotti, I Scotti, E Bozzolo, A Berti, P G Camici, A L Catapano, A A Manfredi, E Ammirati, G D Norata
BACKGROUND AND AIM: Patients with Systemic Lupus Erythematosus (SLE) present increased cardiovascular mortality compared to the general population. Few studies have assessed the long-term development and progression of carotid atherosclerotic plaque in SLE patients. Our aim was to investigate the association of clinical and laboratory markers of disease activity and classical cardiovascular risk factors (CVRF) with carotid atherosclerosis development in SLE patients in a prospective 5-year study...
September 18, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29150290/premature-atherosclerosis-in-premenopausal-women-does-cytokine-balance-play-a-role
#8
Jo-Ann Eastwood, Doris A Taylor, B Delia Johnson, Micheline Resende, Barry L Sharaf, Bina Ahmed, Margo Minissian, Chrisandra Shufelt, Noel Bairey Merz
Contributory risk factors to premature coronary artery disease (CAD) in premenopausal women are poorly understood and data on this subset of women is lacking. There is growing evidence that the process of inflammation is a part of the atherosclerotic process. Mechanistic insights from animal work suggest that the profile of circulating cytokines reflects both endothelial integrity and the presence of immune and progenitor cells. Significant differences in pro- and anti-inflammatory cytokine concentrations between patients with and without CAD exist...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29150289/the-cause-of-multiple-sclerosis-is-autoimmune-attack-of-adenosyltransferase-thereby-limiting-adenosylcobalamin-production
#9
J L Boucher
The pathogenesis of multiple sclerosis (MS) begins with an infection by a bacterium from the class of bacteria that produce and utilize adenosylcobalamin (AdoCbl) and possess an adenosyl transferase enzyme (ATR); these bacteria are the exogenous antigens that cause MS. Human ATR is homologous to bacterial ATR and B cells produce anti-ATR antibodies as an autoimmune response thereby reducing the concentration of ATR and thus limiting production of AdoCbl, one of the two bioactive forms of vitamin B12. The next step in MS pathogenesis is a period of subclinical AdoCbl deficiency over a period of many years resulting in production of odd-carbon-number fatty acids that are incorporated into myelin rendering it antigenic...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29150240/dichotomous-expression-of-tnf-superfamily-ligands-on-antigen-presenting-cells-controls-post-priming-anti-viral-cd4-t-cell-immunity
#10
Yu-Han Chang, Kuan Chung Wang, Kuan-Lun Chu, Derek L Clouthier, Anh T Tran, Miguel S Torres Perez, Angela C Zhou, Ali A Abdul-Sater, Tania H Watts
T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4(+) T cell accumulation and control of chronic lymphocytic choriomeningitis virus (LCMV). We found that type I interferon (IFN-I) induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived APCs and CD80 and CD86 predominantly on classical dendritic cells (cDCs)...
November 13, 2017: Immunity
https://www.readbyqxmd.com/read/29150238/a-t-cell-receptor-locus-harbors-a-malaria-specific-immune-response-gene
#11
Natalija Van Braeckel-Budimir, Stephanie Gras, Kristin Ladell, Tracy M Josephs, Lecia Pewe, Stina L Urban, Kelly L Miners, Carine Farenc, David A Price, Jamie Rossjohn, John T Harty
Immune response (Ir) genes, originally proposed by Baruj Benacerraf to explain differential antigen-specific responses in animal models, have become synonymous with the major histocompatibility complex (MHC). We discovered a non-MHC-linked Ir gene in a T cell receptor (TCR) locus that was required for CD8(+) T cell responses to the Plasmodium berghei GAP5040-48 epitope in mice expressing the MHC class I allele H-2D(b). GAP5040-48-specific CD8(+) T cell responses emerged from a very large pool of naive Vβ8...
November 10, 2017: Immunity
https://www.readbyqxmd.com/read/29149987/inhibition-of-porcine-endogenous-retrovirus-by-multi-targeting-micro-rna-against-long-terminal-region
#12
H-C Chung, V-G Nguyen, W-T Oh, T-M-L Huynh, H-J Moon, J-H Lee, H-K Kim, S-J Park, B-K Park
BACKGROUND: There might be much benefit in xenotransplantation, however, the risk of infections across species barriers remains, especially porcine endogenous retrovirus (PERV). To date, many attempts have been made to knock down active PERVs by inhibitory RNA (RNAi) and micro RNA (miRNA), which target different genes of PERV. There are a few studies that have explored whether targeting promoter regions of PERV could exert an inhibition effect. METHODS: miRNAs were automatically selected based on an online program BLOCK-iT RNAi Designer...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29149979/influence-of-oral-anaerobic-bacteria-on-hematopoietic-stem-cell-transplantation-patients-oral-mucositis-and-general-condition
#13
L Osakabe, A Utsumi, B Saito, Y Okamatsu, H Kinouchi, T Nakamaki, S Hironaka
OBJECTIVE: Oral mucositis (OM) caused by infection facilitated by myelosuppression and immunosuppression can be controlled through oral care. We investigated changes in oral anaerobic bacterial flora during the onset of OM with hematopoietic stem cell transplantation (HSCT). METHODS: This study included 19 patients who underwent HSCT. All received professional oral care before initiating the preparative regimen. We assessed OM, oral health and obtained microbial samples from the oral cavity during 5 assessment points: before initiating the preparative regimen; the day before HSCT (day 1); and at 7, 14, and 30 days after HSCT...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29149426/relationship-between-lat1-expression-and-resistance-to-chemotherapy-in-pancreatic-ductal-adenocarcinoma
#14
Bolag Altan, Kyoichi Kaira, Akira Watanabe, Norio Kubo, Pinjie Bao, Gantumur Dolgormaa, Erkhem-Ochir Bilguun, Kenichiro Araki, Yoshikatsu Kanai, Takehiko Yokobori, Tetsunari Oyama, Masahiko Nishiyama, Hiroyuki Kuwano, Ken Shirabe
PURPOSE: L-type amino acid transporter 1 (LAT1) is linked to tumor cell proliferation, angiogenesis, and survival in various human cancers. Although the expression of LAT1 was identified as a significant prognostic predictor after surgery in patients with pancreatic ductal adenocarcinoma (PDAC), little is known about the clinical significance of LAT1 as a chemotherapeutic resistance factor in PDAC. METHODS: A total of 110 patients with surgically resected PDAC were retrospectively reviewed as the training set...
November 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29149205/kir-content-genotypes-associate-with-carriage-of-hepatitis-b-surface-antigen-e-antigen-and-hbv-viral-load-in-gambians
#15
Louis-Marie Yindom, Maimuna Mendy, Christopher Bodimeade, Caroline Chambion, Peter Aka, Hilton C Whittle, Sarah L Rowland-Jones, Robert Walton
BACKGROUND: Hepatocellular carcinoma (HCC) causes over 800,000 deaths worldwide annually, mainly in low income countries, and incidence is rising rapidly in the developed world with the spread of hepatitis B (HBV) and C (HCV) viruses. Natural Killer (NK) cells protect against viral infections and tumours by killing abnormal cells recognised by Killer-cell Immunoglobulin-like Receptors (KIR). Thus genes and haplotypes encoding these receptors may be important in determining both outcome of initial hepatitis infection and subsequent chronic liver disease and tumour formation...
2017: PloS One
https://www.readbyqxmd.com/read/29147611/chloroquine-supplementation-increases-the-cytotoxic-effect-of-curcumin-against-her2-neu-overexpressing-breast-cancer-cells-in-vitro-and-in-vivo-in-nude-mice-while-counteracts-it-in-immune-competent-mice
#16
L Masuelli, M Granato, M Benvenuto, R Mattera, R Bernardini, M Mattei, G d'Amati, G D'Orazi, A Faggioni, R Bei, M Cirone
Autophagy is usually a pro-survival mechanism in cancer cells, especially in the course of chemotherapy, thus autophagy inhibition may enhance the chemotherapy-mediated anti-cancer effect. However, since autophagy is strongly involved in the immunogenicity of cell death by promoting ATP release, its inhibition may reduce the immune response against tumors, negatively influencing the overall outcome of chemotherapy. In this study, we evaluated the in vitro and in vivo anti-cancer effect of curcumin (CUR) against Her2/neu overexpressing breast cancer cells (TUBO) in the presence or in the absence of the autophagy inhibitor chloroquine (CQ)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147608/the-prognostic-role-of-tumor-infiltrating-t-lymphocytes-in-squamous-cell-carcinoma-of-the-head-and-neck-a-systematic-review-and-meta-analysis
#17
REVIEW
Emma J de Ruiter, Marc L Ooft, Lot A Devriese, Stefan M Willems
Background - The presence of tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment is associated with an improved prognosis and a better response to therapy in different types of cancer. In this systematic review and meta-analysis, we investigated the prognostic value of T cells in head and neck squamous cell carcinoma (HNSCC). Methods - In a systematic review, Pubmed and Embase were searched for publications that investigated the prognostic value of T cells in HNSCC. A meta-analysis was performed including all studies assessing the association between CD3+, CD4+, CD8+, and FoxP3+ TILs and overall survival (OS), disease-free survival (DFS), or locoregional control (LRC)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29146735/reduced-dnmt3a-increases-gdf5-expression-with-suppressed-satellite-cell-differentiation-and-impaired-skeletal-muscle-regeneration
#18
Yukino Hatazawa, Yusuke Ono, Yuma Hirose, Sayaka Kanai, Nobuharu L Fujii, Shuichi Machida, Ichizo Nishino, Takahiko Shimizu, Masaki Okano, Yasutomi Kamei, Yoshihiro Ogawa
DNA methylation is an epigenetic mechanism regulating gene expression. In this study, we observed that DNA methyltransferase 3a (Dnmt3a) expression is decreased after muscle atrophy. We made skeletal muscle-specific Dnmt3a knockout mice (Dnmt3a-KO mice). The regeneration capacity after muscle injury was markedly decreased in Dnmt3a-KO mice. Diminished mRNA and protein expression of Dnmt3a were observed in skeletal muscles as well as in satellite cells, which are important for muscle regeneration, in Dnmt3a-KO mice...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146734/humanized-mice-in-studying-efficacy-and-mechanisms-of-pd-1-targeted-cancer-immunotherapy
#19
Minan Wang, Li-Chin Yao, Mingshan Cheng, Danying Cai, Jan Martinek, Chong-Xian Pan, Wei Shi, Ai-Hong Ma, Ralph W De Vere White, Susan Airhart, Edison T Liu, Jacques Banchereau, Michael A Brehm, Dale L Greiner, Leonard D Shultz, Karolina Palucka, James G Keck
Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, non-obese diabetic (NOD).Cg-Prkdc(scid)IL2rg(tm1Wjl) /Sz (null; NSG) mice were transplanted with human (h)CD34(+) hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patient-derived xenografts [PDX; nonsmall cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft (CDX)...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146716/dynamic-contrast-enhanced-mri-derived-intracellular-water-lifetime-%C3%AF-i-a-prognostic-marker-for-patients-with-head-and-neck-squamous-cell-carcinomas
#20
S Chawla, L A Loevner, S G Kim, W-T Hwang, S Wang, G Verma, S Mohan, V LiVolsi, H Quon, H Poptani
BACKGROUND AND PURPOSE: Shutter-speed model analysis of dynamic contrast-enhanced MR imaging allows estimation of mean intracellular water molecule lifetime (a measure of cellular energy metabolism) and volume transfer constant (a measure of hemodynamics). The purpose of this study was to investigate the prognostic utility of pretreatment mean intracellular water molecule lifetime and volume transfer constant in predicting overall survival in patients with squamous cell carcinomas of the head and neck and to stratify p16-positive patients based upon survival outcome...
November 16, 2017: AJNR. American Journal of Neuroradiology
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