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Eugene Lin, Manjula Kurella Tamura, Maria E Montez-Rath, Glenn M Chertow
Introduction The use of administrative data to capture 30-day readmission rates in end-stage renal disease is challenging since Medicare combines claims from acute care, inpatient rehabilitation (IRF), and long-term care hospital stays into a single "Inpatient" file. For data prior to 2012, the United States Renal Data System does not contain the variables necessary to easily identify different facility types, making it likely that prior studies have inaccurately estimated 30-day readmission rates. Methods For this report, we developed two methods (a "simple method" and a "rehabilitation-adjusted method") to identify acute care, IRF, and long-term care hospital stays from United States Renal Data System claims data, and compared them to methods used in previously published reports...
October 20, 2016: Hemodialysis International
Lis N Velásquez, M Ayelén Milillo, M Victoria Delpino, Aldana Trotta, Pablo Fernández, Roberto G Pozner, Roland Lang, Luciana Balboa, Guillermo H Giambartolomei, Paula Barrionuevo
Brucella abortus is an intracellular pathogen capable of surviving inside of macrophages. The success of B. abortus as a chronic pathogen relies on its ability to orchestrate different strategies to evade the adaptive CD4(+) T cell responses that it elicits. Previously, we demonstrated that B. abortus inhibits the IFN-γ-induced surface expression of MHC class II (MHC-II) molecules on human monocytes, and this phenomenon correlated with a reduction in antigen presentation. However, the molecular mechanisms, whereby B...
October 20, 2016: Journal of Leukocyte Biology
Y Liu, L Huang, H Ye, X Lv
Interferon regulatory factor-7 (IRF-7) is involved in pulmonary infection and pneumonia. Here, a synthetic strategy that combined quantitative structure-activity relationship (QSAR)-based virtual screening and in vitro binding assay was described to identify new and potent mediator ligands of IRF-7 from natural products. In the procedure, a QSAR scoring function was developed and validated using Gaussian process (GP) regression and a structure-based set of protein-ligand affinity data. By integrating hotspot pocket prediction, pharmacokinetics profile analysis and molecular docking calculations, the scoring function was successfully applied to virtual screening against a large library of structurally diverse, drug-like natural products...
October 20, 2016: SAR and QSAR in Environmental Research
Yoshie Kametani, Shino Ohshima, Asuka Miyamoto, Atsuko Shigenari, Masaki Takasu, Noriaki Imaeda, Tatsuya Matsubara, Masafumi Tanaka, Takashi Shiina, Hiroshi Kamiguchi, Ryuji Suzuki, Hitoshi Kitagawa, Jerzy K Kulski, Noriaki Hirayama, Hidetoshi Inoko, Asako Ando
The class I major histocompatibility complex (MHC) presents self-developed peptides to specific T cells to induce cytotoxity against infection. The MHC proteins are encoded by multiple loci that express numerous alleles to preserve the variability of the antigen-presenting ability in each species. The mechanism regulating MHC mRNA and protein expression at each locus is difficult to analyze because of the structural and sequence similarities between alleles. In this study, we examined the correlation between the mRNA and surface protein expression of swine leukocyte antigen (SLA)-1*0401 after the stimulation of peripheral blood mononuclear cells (PBMCs) by Staphylococcus aureus superantigen toxic shock syndrome toxin-1 (TSST-1)...
2016: PloS One
Erica L Heipertz, Jourdan Harper, Wendy E Walker
IFN regulatory factor (IRF)3 plays a detrimental role in the cecal ligation and puncture (CLP) mouse model of sepsis. However, it is unclear which pathway activates IRF3 in this context. In this report we investigate two pathways that activate IRF3: the Stimulator of Interferon Genes (STING) pathway (which senses cytosolic DNA) and the TIR-domain-containing adapter-inducing interferon-β (TRIF) pathway (which sense dsRNA and LPS via Toll-like receptor (TLR) 3 and 4). Initially, we examine the impact of these pathways using a severe CLP model (∼90% mortality)...
October 17, 2016: Shock
Nicole C Droz, Stephanie D Mathew
After presenting with nonspecific symptoms, a 52-year-old female was found to have a 3.4 × 2.6 cm retroperitoneal mass resulting in hydronephrosis on abdominal computed tomography scan. After extensive workup including surgical debulking, excisional biopsy, and autoimmune panel, she was found to have idiopathic retroperitoneal fibrosis (IRF) with negative staining for immunoglogulin G4 (IgG4). Two years after presentation, the patient developed dyspnea, cough, and xerostomia. Repeat anti-Sjögren Syndrome A and anti-Sjögren Syndrome B titers and labial gland biopsy confirmed the diagnosis of concomitant Sjögren's syndrome (SS)...
October 2016: Military Medicine
Ying Wang, Tao Liu, Ning Yang, Shuo Xu, Xingang Li, Donghai Wang
Glioblastoma (GBM) is a highly malignant brain tumor characterized by invasion tendency. Macrophage infiltration is associated with GBM invasion, but the mechanisms remain unclear. Hypoxia is an outstanding characteristic of GBM tissue. Hypoxia microenvironment modulates the biological behaviors of both tumor cells and infiltrated immune cells, including macrophages. In the present study, we analyzed the effects of hypoxia and macrophages on invasion of GBM cells and its potential mechanisms. We found that both hypoxia and macrophage supernatant promoted GBM cells invasion and matrix metalloproteinase (MMP)-9 expression, and hypoxia modulated the invasive activity of GBM cells by upregulating their CCR5 expression...
October 13, 2016: Oncology Reports
Yu Chen, Xiaoling Deng, Junfang Deng, Jiehua Zhou, Yuping Ren, Shengxuan Liu, Deborah J Prusak, Thomas G Wood, Xiaoyong Bao
Human metapneumovirus (hMPV) is a major cause of lower respiratory infection in young children. Repeated infections occur throughout life, but its immune evasion mechanisms are largely unknown. We recently found that hMPV M2-2 protein elicits immune evasion by targeting mitochondrial antiviral-signaling protein (MAVS), an antiviral signaling molecule. However, the molecular mechanisms underlying such inhibition are not known. Our mutagenesis studies revealed that PDZ-binding motifs, 29-DEMI-32 and 39-KEALSDGI-46, located in an immune inhibitory region of M2-2, are responsible for M2-2-mediated immune evasion...
October 13, 2016: Virology
Gabrielle M Harris, Janice Collins-McNeil, Qing Yang, Vu Q C Nguyen, Mark A Hirsch, Charles F Rhoads, Tami Guerrier, J George Thomas, Terrence M Pugh, Deanna Hamm, Carol Pereira, Janet Prvu Bettger
PURPOSE: To examine the prevalence of poststroke depression (PSD) among African American stroke survivors and the association of depression with functional status at inpatient rehabilitation facility (IRF) discharge. METHODS: Secondary data analysis was conducted of a patient cohort who received care at 3 IRFs in the United States from 2009 to 2011. Functional status was measured by the Functional Independence Measure (FIM). Multiple linear regression models were used to examine associations of PSD and FIM motor and cognitive scores...
October 6, 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Yuanyuan Guo, Zhiyin Yang, Shan Wu, Peng Xu, Yinbo Peng, Min Yao
The inflammatory response is essential for normal cutaneous wound healing. Macrophages, as critical inflammatory cells, coordinate inflammation and angiogenesis phases during wound healing. It has been reported that the transcription factor interferon regulatory factor 8 (IRF8), a member of the IRF family, plays a critical role in the development and function of macrophages and is associated with inflammation. However, the role of IRF8 in cutaneous wound healing and its underlying mechanism remain elusive. Through immunohistochemical (IHC) staining, we showed that IRF8 is involved in the wound repair process in mice and patients...
October 5, 2016: Inflammation
Seho Cha, Joonho Choe, Taegun Seo
Kaposi's sarcoma-associated herpesvirus (KSHV) is an etiological agent of Kaposi's sarcoma and primary effusion lymphoma. Like other herpesviruses, KSHV has two distinct life cycles: latent and lytic. Among KSHV latent genes, viral interferon regulatory factor 3 (vIRF3), which shares homology with cellular IRFs, is a multifunctional protein. To identify unknown functions of vIRF3, we performed luciferase-reporter assays in the presence of vIRF3. These analyses revealed that overexpression of vIRF3 inhibited T-cell factor (TCF)-dependent transcriptional activity...
October 28, 2016: Biochemical and Biophysical Research Communications
Fan-Bin Zhan, Han Liu, Rui-Fang Lai, Ivan Jakovlić, Wei-Min Wang
Interferon regulatory factors (irfs) are a family of genes that encode transcription factors with important roles in regulating the expression of Type I interferons (IFNs) and other genes associated with related pathways. irfs have multitudinous functions in growth, development and regulation of oncogenesis. In this study, three irf family members (irf2, irf7, irf9) were identified and characterized in Megalobrama amblycephala at the mRNA and amino acid levels. M. amblycephala irfs share a high sequence homology with other vertebrate irfs...
September 25, 2016: Developmental and Comparative Immunology
Kirill Alekseyev, Armando Iannicello, Nnabugo D Ozurumba, Shahrokh S Bemanian, Travis M Rosenkranz, Giuseppe Amore, Marc Ross, Adrian Cristian
No abstract text is available yet for this article.
September 2016: PM & R: the Journal of Injury, Function, and Rehabilitation
Ryo Hayakari, Tomoh Matsumiya, Fei Xing, Hidemi Yoshida, Makoto Hayakari, Tadaatsu Imaizumi
The cytoplasmic viral sensor retinoic acid-inducible gene-I (RIG-I), which is also known as an IFN-stimulated gene (ISG), senses viral RNA to activate antiviral signaling. It is therefore thought that RIG-I is regulated in a STAT1-dependent manner. Although RIG-I-mediated antiviral signaling is indispensable for the induction of an appropriate adaptive immune response, the mechanism underlying the regulation of RIG-I expression remains elusive. Here, we examined the direct regulation of RIG-I expression by interferon regulatory factor 3 (IRF-3), which is an essential molecule for antiviral innate immunity...
2016: PloS One
Zacharey Guinn, Anna T Lampe, Deborah M Brown, Thomas M Petro
Interferon Regulatory Factor (IRF)3 is a crucial transcription factor during innate immune responses. Here we show IRF3 also has a role in adaptive T cell immune responses. Expression of IFN-γ, IL-17, and Granzyme B (GrB) during in vitro T cell responses was impaired when either dendritic cells (DCs) or T cells were derived from IRF3KO mice. Unexpectedly, IRF3-dependent NK-activating molecule (INAM), which is an NK cell activating factor of the DC innate immune response, was induced during the T cell response...
September 4, 2016: Cellular Immunology
Christian H Gabriel, Fridolin Gross, Martin Karl, Heike Stephanowitz, Anna Floriane Hennig, Melanie Weber, Stefanie Gryzik, Ivo Bachmann, Katharina Hecklau, Jürgen Wienands, Johannes Schuchhardt, Hanspeter Herzel, Andreas Radbruch, Eberhard Krause, Ria Baumgrass
Transcription factors of the nuclear factor of activated T cell (NFAT)-family are essential for antigen-specific T cell activation and differentiation. Their cooperative DNA binding with other transcription factors, such as AP1-proteins (FOS, JUN, JUNB), FOXP3, IRFs and EGR1, dictate the gene regulatory action of NFATs. To identify as yet unknown interaction partners of NFAT, we purified biotin tagged NFATc1/αA, NFATc1/βC and NFATc2/C protein-complexes and analyzed their components by SILAC-based mass spectrometry...
September 16, 2016: Journal of Biological Chemistry
Tae Whan Kim, Seunghee Hong, Yin Lin, Elise Murat, HyeMee Joo, Taeil Kim, Virginia Pascual, Yong-Jun Liu
Type I IFNs are crucial mediators of human innate and adaptive immunity and are massively produced from plasmacytoid dendritic cells (pDCs). IFN regulatory factor (IRF)7 is a critical regulator of type I IFN production when pathogens are detected by TLR 7/9 in pDC. However, hyperactivation of pDC can cause life-threatening autoimmune diseases. To avoid the deleterious effects of aberrant pDC activation, tight regulation of IRF7 is required. Nonetheless, the detailed mechanisms of how IRF7 transcription is regulated in pDC are still elusive...
September 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
David Millrine, Mami Tei, Yohannes Gemechu, Tadamitsu Kishimoto
Immunomodulatory drugs (IMiDs) are a family of compounds derived from thalidomide. Binding of the IMiD molecule to the Lon protease Cereblon initiates the degradation of substrates via the ubiquitin proteasome pathway. Here, we show that Cereblon forms a complex with Rabex-5, a regulator of immune homeostasis. Treatment with lenalidomide prevented the association of Cereblon with Rabex-5. Conversely, mutation of the IMiD binding site increased Cereblon-Rabex-5 coimmunoprecipitation. The thalidomide binding region of Cereblon therefore regulates the formation of this complex...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
Moses Okpeku, Ali Esmailizadeh, Adeniyi C Adeola, Liping Shu, Yesheng Zhang, Yangzi Wang, Timothy M Sanni, Ikhide G Imumorin, Sunday O Peters, Jiajin Zhang, Yang Dong, Wen Wang
The immune systems are fundamentally vital for evolution and survival of species; as such, selection patterns in innate immune loci are of special interest in molecular evolutionary research. The interferon regulatory factor (IRF) gene family control many different aspects of the innate and adaptive immune responses in vertebrates. Among these, IRF3 is known to take active part in very many biological processes. We assembled and evaluated 1356 base pairs of the IRF3 gene coding region in domesticated goats from Africa (Nigeria, Ethiopia and South Africa) and Asia (Iran and China) and the wild goat (Capra aegagrus)...
2016: PloS One
Hirotomo Nakaoka, Masaki Mogi, Jun Suzuki, Harumi Kan-No, Li-Juan Min, Jun Iwanami, Masatsugu Horiuchi
We previously reported interferon regulatory factor (IRF) 1 plays physiological roles in "growth"-regulated angiotensin II type 2 (AT2) receptor expression in fibroblasts. Here, we investigated whether IRF-1 is involved in attenuation of vascular remodeling in association with AT2 receptor upregulation. Neointimal area in injured artery after 14 days of cuff placement was significantly increased in IRF-1 knockout mice (IRF-1KO) and AT2 receptor knockout mice (AT2KO) compared with wild-type mice (WT: C57BL/6J)...
October 2016: Journal of the American Society of Hypertension: JASH
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