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Richard Lindqvist, Filip Mundt, Jonathan D Gilthorpe, Silke Wölfel, Nelson O Gekara, Andrea Kröger, Anna K Överby
BACKGROUND: Neurotropic flaviviruses such as tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV), West Nile virus (WNV), and Zika virus (ZIKV) are causative agents of severe brain-related diseases including meningitis, encephalitis, and microcephaly. We have previously shown that local type I interferon response within the central nervous system (CNS) is involved in the protection of mice against tick-borne flavivirus infection. However, the cells responsible for mounting this protective response are not defined...
October 24, 2016: Journal of Neuroinflammation
Hongbo Chen, Yinan Yao, Yifan Wang, Hua Zhou, Tianxiang Xu, Jing Liu, Guocheng Wang, Yongfeng Zhang, Xiang Chen, Qingwei Liu, Peng Huang, Rongbin Yu
BACKGROUND: HLA-DM gene, which is related to antigen processing and presentation and located in the non-classical class-II region of human leukocyte antigen (HLA) region, may play a crucial role in chronic hepatitis C virus (HCV) infection treatment outcomes. The study was conducted to evaluate the role of the variant of several single nucleotide polymorphisms (SNPs) in HLA-DM gene in HCV treatment outcomes. METHODS: We genotyped four SNPs from the candidate genes (HLA-DMA and DMB) in 336 patients who were treated with pegylated interferon-alpha and ribavirin (PEG IFN-α/RBV)...
October 20, 2016: International Journal of Environmental Research and Public Health
Brenden Van Wyk, Marlene Snider, Erin Scruten, Sylvia van Drunen Littel-van den Hurk, Scott Napper
As a part of their pathogenic mechanism, many pathogens causing persistent infections, including bovine viral diarrhea virus (BVDV), immunosuppress their hosts, often by limiting the ability to either produce, or respond to, interferon. The objective of this study was to quantify the extent to which an acute infection of cattle with a non-cytopathic strain of BVDV induces interferon responses and to establish the functionality of these responses. Functionality of responses was investigated using a bovine specific peptide array to monitor kinase-mediated signal transduction activity within peripheral blood mononuclear cells (PBMCs) at time points corresponding to the interferon gamma (IFN-γ) and alpha (IFN-α) responsive phases of acute BVDV infection...
November 15, 2016: Veterinary Microbiology
Yuichi Arai, Keiichi Ito, Kazuyoshi Tachi, Akio Koga, Yusuke Shinchi, Ayako Masunaga, Makoto Isono, Tomohiko Asano
A 73-year-old male patient underwent a right nephrectomy for renal cell carcinoma in 2008, and interferon-alpha was initiated as adjuvant treatment. Computed tomography (CT) scans showed lymphadenopathy above the left diaphragm, and treatment with interferon-2 was subsequently initiated in 2009. Nasal bleeding manifested in February 2010, and CT scans showed a soft-tissue density mass mainly located in the ethmoid sinus. A biopsy of the lesion was performed, and metastatic renal cell carcinoma was diagnosed...
September 2016: Hinyokika Kiyo. Acta Urologica Japonica
Laurent Alric, Caroline Besson, Nathanael Lapidus, Juliette Jeannel, Jean-Marie Michot, Patrice Cacoub, Danielle Canioni, Stanislas Pol, Frédéric Davi, Pascaline Rabiega, Loic Ysebaert, Delphine Bonnet, Olivier Hermine
: Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHLs). Evaluation of the efficacy and safety profiles of different antiviral therapies in HCV patients with B-NHL is warranted. METHODS: First, we evaluated the sustained virologic response (SVR) and safety of Peg-interferon-alpha (Peg-IFN) + ribavirin +/- first protease inhibitors (PI1s) therapy in 61 HCV patients with B-NHL enrolled in a nationwide observational survey compared with 94 matched HCV-infected controls without B-NHL...
2016: PloS One
Gerson Dierley Keppeke, Monica Simon Prado, Eunice Nunes, Sandro Felix Perazzio, Silvia Helena Rodrigues, Maria Lucia Gomes Ferraz, Edward K L Chan, Luis Eduardo Coelho Andrade
Some HCV patients using ribavirin and interferon alpha (IFN-α) develop anti-rods and rings (RR) autoantibodies, the main target of which is inosine monophosphate dehydrogenase (IMPDH), the rate-determining enzyme in de novo GTP biosynthesis. In vitro inhibition of IMPDH by ribavirin induces RR formation. Here we investigate whether other commonly used drugs that interfere with GTP biosynthesis can induce RR structures in vitro and vivo and elicit generation of autoantibodies. HEp-2 cells treated for 24h with ribavirin, mycophenolic acid (MPA), azathioprine, methotrexate or acyclovir were positive for RR structures...
October 13, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Áine M Prendergast, Andrea Kuck, Mieke van Essen, Simon Haas, Sandra Blaszkiewicz, Marieke A G Essers
In the bone marrow, endothelial cells are a major component of the hematopoietic stem cell vascular niche and are a first line of defense against inflammatory stress and infection. The primary response of an organism to infection involves the synthesis of immune-modulatory cytokines, including interferon alpha. In the bone marrow, interferon alpha induces rapid cell cycle entry of hematopoietic stem cells in vivo However, the effect of interferon alpha on bone marrow endothelial cells has not been described...
October 14, 2016: Haematologica
Barbara Spolaore, Samanta Raboni, Abhijeet Ajit Satwekar, Antonella Grigoletto, Anna Mero, Isabella Monia Montagner, Antonio Rosato, Gianfranco Pasut, Angelo Fontana
Interferon alpha (IFN α) subtypes are important protein drugs that have been used to treat infectious diseases and cancers. Here, we studied the reactivity of IFN α-2b to microbial transglutaminase (TGase) with the aim to obtain a site-specific conjugation of this protein drug. Interestingly, TGase allowed the production of two mono-derivatized isomers of IFN with high yields. Characterization by mass spectrometry of the two conjugates indicated that they are exclusively modified at the level of Gln101 if the protein is reacted in the presence of an amino containing ligand (i...
October 12, 2016: Bioconjugate Chemistry
Sabine Blum, Filipe Martins, Lorenzo Alberio
The discovery of JAK2 V617F mutation in the mid-2000s started to fill the gap between clinical presentation of polycythemia vera (PV), first described by Vaquez at the end of the 19th century, and spontaneous erythroid colony formation, reported by Prchal and Axelrad in the mid-1970s. The knowledge on this mutation brought an important insight to our understanding of PV pathogenesis and led to a revision of the World Health Organization diagnostic criteria in 2008. JAK-STAT is a major signaling pathway implicated in survival and proliferation of hematopoietic precursors...
2016: Journal of Blood Medicine
S Hraiech, J Bordes, J L Mège, X de Lamballerie, R Charrel, Y Bechah, B Pastorino, C Guervilly, J M Forel, M Adda, J M Rolain, H Lepidi, D Raoult, S Lehingue, L Papazian
OBJECTIVES: Cytomegalovirus (CMV) reactivation in intensive care unit patients may increase mortality and favour bacterial pneumonia. We developed a murine model to compare the severity of staphylococcal pneumonia after CMV reactivation and in CMV-negative mice. METHODS: Balb/c mice were primo-infected with murine cytomegalovirus (MCMV n=90) or received saline (control n=90). After latency, all mice underwent caecal ligation and puncture to trigger MCMV reactivation in MCMV primary-infected mice...
October 5, 2016: Clinical Microbiology and Infection
Marta Martin-Subero, Crisanto Diez-Quevedo
This paper aims to review the epidemiology and management of mental disorders in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients, the need for antiviral therapy in this specific population, and current treatment strategies for HIV/HCV patients with psychiatric and/or substance use disorders. This is a narrative review. Data was sourced from electronic databases and was not limited by language or date of publication. HIV infection has become a survivable chronic illness. Prevalence of HCV infection among HIV-infected patients is high ranging from 50% to 90%...
September 26, 2016: Psychiatry Research
Anne-Sylvia Sacri, Annelyse Bruwier, Geneviève Baujat, Sylvain Breton, Stéphane Blanche, Tracy A Briggs, Brigitte Bader-Meunier
Childhood-onset chronic and refractory cytopenias are rare and may be genetic in etiology. We report three pediatric cases of severe autoimmune thrombocytopenia or anemia associated with growth retardation and spastic diplegia with intracranial calcification. The identification of platyspondyly and metaphyseal lesions suggested a potential diagnosis of spondyloenchondrodysplasia (SPENCD), which was confirmed with the identification of biallelic ACP5 mutations. Two patients demonstrated elevated serum interferon alpha levels...
October 8, 2016: Pediatric Blood & Cancer
Murali Ganesan, Larisa Y Poluektova, Dean J Tuma, Kusum K Kharbanda, Natalia A Osna
BACKGROUND: Alcohol consumption exacerbates the pathogenesis of hepatitis C virus (HCV) infection and worsens disease outcomes. The exact reasons are not clear yet, but they might be partially attributed to the ability of alcohol to further suppress the innate immunity. Innate immunity is known to be already decreased by HCV in liver cells. METHODS: In this study, we aimed to explore the mechanisms of how alcohol metabolism dysregulates IFNα signaling (STAT1 phosphorylation) in HCV(+) hepatoma cells...
September 26, 2016: Alcoholism, Clinical and Experimental Research
Giórgia de Souza Marasca, André Luiz Machado, Nélson Alexandre Kretzmann, Adaliany Cecília da Silva Souza, Angelo Alves de Mattos, Dimas Kliemann, Cristiane Valle Tovo, Ana Beatriz Gorini da Veiga
Background: Due to the high prevalence of co-infection by hepatitis C virus (HCV) and human immunodeficiency virus (HIV) and the severity of these infections, the understanding of the biological mechanisms involved in these processes, including viral behavior and host genetic profile, is of great importance for patient treatment and for public health policies.Some single nucleotide polymorphisms (SNPs) in the human genome, such as the SNP rs1045642 (C3435T) in the MDR1 gene, have been reported to be associated to the sustained virological response (SVR) to HCV treatment in HCV-HIV co-infected patients...
October 2016: Arquivos de Gastroenterologia
Yesim Ozguler, Gulen Hatemi, Serdal Ugurlu, Emire Seyahi, Melike Melikoglu, Sermin Borekci, Ersan Atahan, Gul Ongen, Vedat Hamuryudan
The use of anti-TNF agents is associated with an increased risk of tuberculosis (TB) and anti-TNF agents are stopped when active TB develops. However, discontinuation of treatment can result in flare of the underlying disease. The charts of 22 patients who developed active TB among a cohort of 2754 patients using anti-TNF agents between 2001 and 2013 were reviewed retrospectively. Patients restarting biologics during further follow-up were identified. One patient with miliary TB died within 1 month. A biologic agent was restarted in 16 of the remaining 21 patients (76 %)...
October 3, 2016: Rheumatology International
Tue Kruse Rasmussen
Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are lifelong diseases with increased mortality and chronic pains. They are both characterized by immunological imbalances causing the immune system attack and destroy the bodies own tissues (called autoimmune disease). The best treatment, we are currently able to offer these patients, cause significant side-effects and can not prevent significant loss of quality of life. At the heart of the disease mechanisms in RA and SLE are subsets of immune cells called T and B cells...
October 2016: Danish Medical Journal
Alessia Mennitto, Paolo Grassi, Raffaele Ratta, Elena Verzoni, Michele Prisciandaro, Giuseppe Procopio
Renal cell carcinoma (RCC) is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Cytokine-based immunotherapies, including interferon-α and interleukin-2, have been used for the treatment of metastatic RCC (mRCC). Long-term responses and complete remissions were observed, but durable clinical benefit efficacy in the overall population was limited and associated with significant toxicity. As a consequence, new generation agents targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways replaced interferon alpha (IFN-α)...
October 2016: Therapeutic Advances in Urology
Celalettin Ustun, Michel Arock, Hanneke C Kluin-Nelemans, Andreas Reiter, Wolfgang R Sperr, Tracy George, Hans-Peter Horny, Karin Hartmann, Karl Sotlar, Gandhi Damaj, Olivier Hermine, Srdan Verstovsek, Dean D Metcalfe, Jason Gotlib, Cem Akin, Peter Valent
Systemic mastocytosis is a heterogeneous disease characterized by the accumulation of neoplastic mast cells in the bone marrow and other organ organs/tissues. Mutations in KIT, most frequently KIT D816V, are detected in over 80% of all systemic mastocytosis patients. While most systemic mastocytosis patients suffer from an indolent disease variant, some present with more aggressive variants, collectively called "advanced systemic mastocytosis", which include aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic, clonal non mast cell-lineage disease, and mast cell leukemia...
October 2016: Haematologica
Chien-Cheng Liu, Yong-Jing Gao, Hao Luo, Temugin Berta, Zhen-Zhong Xu, Ru-Rong Ji, Ping-Heng Tan
It is well known that interferons (IFNs), such as type-I IFN (IFN-α) and type-II IFN (IFN-γ) are produced by immune cells to elicit antiviral effects. IFNs are also produced by glial cells in the CNS to regulate brain functions. As a proinflammatory cytokine, IFN-γ drives neuropathic pain by inducing microglial activation in the spinal cord. However, little is known about the role of IFN-α in regulating pain sensitivity and synaptic transmission. Strikingly, we found that IFN-α/β receptor (type-I IFN receptor) was expressed by primary afferent terminals in the superficial dorsal horn that co-expressed the neuropeptide CGRP...
September 27, 2016: Scientific Reports
A Florido-Rodriguez, J Eiris-Punal, F Barros-Angueira, L Toledo-Bravo de Laguna, A Santana-Artiles, I Sebastian-Garcia, A Santana-Rodriguez, J C Cabrera-Lopez
INTRODUCTION: Aicardi-Goutieres syndrome is a rare progressive subacute encephalopathy of early onset - generally in the first year of life - characterised by psychomotor retardation, microcephaly, alterations in the white matter of the brain, intracranial calcifications, pleocytosis and elevated levels of interferon alpha in the cerebrospinal fluid. It is associated to an increase in the expression of genes stimulated by interferon in peripheral blood, a fact known as the interferon signature...
October 1, 2016: Revista de Neurologia
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