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https://www.readbyqxmd.com/read/29458220/incidence-of-autoimmune-and-related-disorders-after-resolution-of-endogenous-cushing-syndrome-in-children
#1
Christina Tatsi, Meg Keil, Charalampos Lyssikatos, Elena Belyavskaya, Constantine A Stratakis, Maya B Lodish
Glucocorticoids are widely used for immunosuppression in autoimmune diseases. After the resolution of hypercortisolemia, the immune system recovers allowing for autoimmune diseases to manifest. Here we investigated the presence of autoimmune and related diseases that developed after cure of endogenous Cushing syndrome (CS) in children. We identified 129 children who were diagnosed and successfully treated for endogenous CS at the National Institutes of Health from 1997 until 2017, and who were followed for at least 6 months after treatment...
February 19, 2018: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29458219/clinical-endocrine-and-imaging-characteristics-of-patients-with-primary-hypophysitis
#2
Anna Angelousi, Carolina Cohen, Soledad Sosa, Karina Danilowicz, Lina Papanastasiou, Marina Tsoli, Aparna Pal, Georgios Piaditis, Ashley Grossman, Gregory Kaltsas
Primary hypophysitis (PH) is a rare disease with a poorly-defined natural history. Our aim was to characterise patients with PH at presentation and during prolonged follow-up. Observational retrospective study of 22 patients was conducted from 3 centres. In 14 patients, PH was confirmed histologically and in the remaining 8 clinically, after excluding secondary causes of hypophysitis. All patients had hormonal and imaging investigations before any treatment. Median follow up was 48 months (25-75%: 3-60). There was a female predominance with a female/male ratio: 3...
February 19, 2018: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29458130/impact-of-rna-polymerase-i-inhibitor-cx-5461-on-viral-kinase-dependent-and-independent-cytomegalovirus-replication
#3
Kristen N Westdorp, Scott S Terhune
Human cytomegalovirus (HCMV) infections cause congenital birth defects and disease in immunosuppressed individuals. Antiviral compounds can control infection yet their use is restricted due to concerns of toxicity and the emergence of drug resistant strains. We have evaluated the impact of an RNA Polymerase I (Pol I) inhibitor, CX-5461 on HCMV replication. CX-5461 inhibits Pol I-mediated ribosomal DNA transcription by binding G-quadruplex DNA structures and also activates cellular stress response pathways. The addition of CX-5461 at both early and late stages of the HCMV infection inhibited viral DNA synthesis and virus production...
February 16, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29458071/b-cells-in-operational-tolerance
#4
REVIEW
M Chesneau, R Danger, J-P Soulillou, S Brouard
Transplantation is currently the therapy of choice for endstage organ failure even though it requires long-term immunossuppresive therapy, with its numerous side effects, for acceptance of the transplanted organ. In rare cases however, patients develop operational tolerance, that is, graft survival without immunosuppression. Studies conducted on these patients reveal genetic, phenotypic, and functional signatures. They provide a better understanding of the immunological mechanisms involved in operational tolerance and define biomarkers that could be used to adapt immunosuppressive treatment to the individual, safely reduce immunosuppression doses, and ideally and safely guide immunosuppression withdrawal...
February 16, 2018: Human Immunology
https://www.readbyqxmd.com/read/29457839/brincidofovir-as-salvage-therapy-for-adenovirus-disease-in-intestinal-transplant-recipients
#5
Nimisha Sulejmani, Shunji Nagai, Mohamed Safwan, Michael D Rizzari, Mohammad Raoufi, Marwan S Abouljoud, Mayur Ramesh
Adenoviruses are double-stranded DNA viruses that typically cause mild self-limiting respiratory, ocular, and gastrointestinal infections. In immunocompromised patients, especially transplant recipients, the infection can be severe, with dissemination and multiorgan failure. In intestinal transplant recipients, the incidence is as high as 57%. To our knowledge, no standardized guidelines or United States Food and Drug Administration-approved medications exist for the treatment of adenovirus disease. We describe two isolated intestinal transplant recipients who developed adenovirus disease (viremia with viral enteritis) that was managed with a new experimental drug, brincidofovir (an oral lipid conjugate prodrug of cidofovir), as salvage therapy...
February 19, 2018: Pharmacotherapy
https://www.readbyqxmd.com/read/29457705/regulation-of-specialised-metabolites-in-actinobacteria-expanding-the-paradigms
#6
Paul A Hoskisson, Lorena T Fernández-Martínez
The increase in availability of actinobacterial whole genome sequences has revealed huge numbers of specialised metabolite biosynthetic gene clusters, encoding a range of bioactive molecules such as antibiotics, antifungals, immunosuppressives and anticancer agents. Yet the majority of these clusters are not expressed under standard laboratory conditions in rich media conditions. Emerging data from studies of specialised metabolite biosynthesis suggest that the diversity of regulatory mechanisms is greater than previously thought and these act at multiple levels, through a range of signals such as nutrient limitation, intercellular signalling and competition with other organisms...
February 19, 2018: Environmental Microbiology Reports
https://www.readbyqxmd.com/read/29457215/the-effect-of-anaesthetic-technique-during-primary-breast-cancer-surgery-on-neutrophil-lymphocyte-ratio-platelet-lymphocyte-ratio-and-return-to-intended-oncological-therapy
#7
A Ní Eochagáin, D Burns, B Riedel, D I Sessler, D J Buggy
Inflammation and immunosuppression contribute to the pathogenesis of cancer. An increased neutrophil-lymphocyte ratio reflects these processes and is associated with adverse cancer outcomes. Whether anaesthetic technique for breast cancer surgery influences these factors, and potentially cancer recurrence, remains unknown. We conducted a secondary analysis in patients enrolled in an ongoing trial of anaesthetic technique on breast cancer recurrence. The primary hypothesis was that postoperative neutrophil-lymphocyte ratio is lower in patients allocated to receive propofol-paravertebral rather than inhalational agent-opioid anaesthesia for primary breast cancer surgery...
February 19, 2018: Anaesthesia
https://www.readbyqxmd.com/read/29457021/difficult-renal-pathological-classification-in-a-case-of-pediatric-nephrotic-syndrome
#8
Hiroshi Yamaguchi, Atsutoshi Shiratori, Taku Nakagawa, Kyoko Kanda, Shigeo Hara, Norishige Yoshikawa, Ryojiro Tanaka
The underlying histopathology is very important in determining patient management, as the histopathology usually has direct repercussions on the treatment response and clinical course. However, the impact of the method used to assess renal biopsies, i.e., light microscopy (LM), immunofluorescence (IF), and electron microscopy (EM), on the occurrence of a difficult biopsy classification in the native kidneys of pediatric nephrotic patients is unknown. A 12-month-old Japanese boy was diagnosed with nephrotic syndrome (NS); he was administered prednisolone (60 mg/m2 /day), and a continuous albumin infusion was started...
September 2017: Case Reports in Nephrology and Dialysis
https://www.readbyqxmd.com/read/29456648/immunosuppressive-effects-of-hydroxychloroquine-and-artemisinin-combination-therapy-via-the-nuclear-factor-%C3%AE%C2%BAb-signaling-pathway-in-lupus-nephritis-mice
#9
Ning Liang, Yanchun Zhong, Jie Zhou, Bihao Liu, Ruirui Lu, Yezhi Guan, Qi Wang, Chunlin Liang, Yu He, Yuan Zhou, Jianping Song, Jiuyao Zhou
Lupus nephritis (LN) is one of the most common and severe manifestations of systemic lupus erythematosus, leading to permanent renal damage and chronic kidney disease. Hydroxychloroquine (HCQ) serves a protective role against lupus-associated clinical manifestations and medical complications; however, it results in numerous adverse reactions, limiting its long-term use. The aim of the present study was to investigate the combined effect of HCQ and artemisinin (ART) on LN, and to elucidate the underlying mechanisms...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29456539/generation-of-human-immunosuppressive-myeloid-cell-populations-in-human-interleukin-6-transgenic-nog-mice
#10
Asami Hanazawa, Ryoji Ito, Ikumi Katano, Kenji Kawai, Motohito Goto, Hiroshi Suemizu, Yutaka Kawakami, Mamoru Ito, Takeshi Takahashi
The tumor microenvironment contains unique immune cells, termed myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) that suppress host anti-tumor immunity and promote tumor angiogenesis and metastasis. Although these cells are considered a key target of cancer immune therapy, in vivo animal models allowing differentiation of human immunosuppressive myeloid cells have yet to be established, hampering the development of novel cancer therapies. In this study, we established a novel humanized transgenic (Tg) mouse strain, human interleukin (hIL)-6-expressing NOG mice (NOG-hIL-6 transgenic mice)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29456529/challenges-and-opportunities-for-biomarkers-of-clinical-response-to-ahsct-in-autoimmunity
#11
Kristina M Harris, Tingting Lu, Noha Lim, Laurence A Turka
Autoimmunity represents a broad category of diseases that involve a variety of organ targets and distinct autoantigens. For patients with autoimmune diseases who fail to respond to approved disease-modifying treatments, autologous hematopoietic stem cell transplantation (AHSCT) after high-dose immunosuppressive therapy provides an alternative strategy. Although more than 100 studies have been published on AHSCT efficacy in autoimmunity, the mechanisms that confer long-term disease remission as opposed to continued deterioration or disease reactivation remain to be determined...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29456214/outcome-of-renal-transplant-recipients-with-cytomegalovirus-and-bk-polyomavirus-co-infection-nephropathy
#12
Anupma Kaul, Shashi Kumar, Dharmendra Bhaduaria, Vinita Agrawal, R K Sharma, Narayan Prasad, Amit Gupta, Rishi Kumar
Reactivation of cytomegalovirus (CMV) and BK polyomavirus (BKV) can result in virus-associated tubulointerstitial nephritis in renal allografts. All those renal biopsies reported as viral cytopathic were isolated and examined by two independent renal histopathologists from our institute and classified as CMV, BKV, and CMV-BKV coinfection-associated viral cytopathic changes with confirmation through polymerase chain reaction technology in either serum or urine or both. All twenty patients were categorized as 10 in CMV, four in BKV, and six were in CMV-BKV coinfection...
January 2018: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/29456097/the-timing-of-early-therapeutic-strategies-has-a-significant-impact-on-crohn-s-disease-prognosis
#13
Cláudia Camila Dias, Francisco Portela, Samuel Fernandes, Paula Ministro, Paula Lago, Isadora Rosa, Luis Correia, Fernando Magro
BACKGROUND: Abdominal surgery and immunosuppressive pharmacological treatments are two different therapeutic options used to manage Crohn disease. This study aimed to determine whether the timing of these interventions had an impact on patients' prognosis. METHOD: This manuscript entails a retrospective analysis of a multicentric cohort involving 498 CD patients that had bowel surgery after diagnosis and prior to immunosuppression treatments. Two endpoints were considered: the occurrence of disabling disease and the need to undergo further bowel surgeries...
February 1, 2018: Digestive and Liver Disease
https://www.readbyqxmd.com/read/29456038/increase-of-natural-killer-cells-in-children-with-liver-transplantation-acquired-food-allergy
#14
F Mori, C Angelucci, A Cianferoni, S Barni, G Indolfi, A Casini, G Mangone, M Materassi, N Pucci, C Azzari, E Novembre
BACKGROUND: Transplantation-acquired food allergies (TAFA) are frequently reported and considered to be caused by immunosuppressive therapy. The aim of this study was to investigate the allergic and immunologic responses in children who had liver or kidney transplantations. METHODS: Twelve children receiving liver transplantations and 10 children receiving kidney transplantations were investigated. All children underwent the allergy work-up and in most of them, lymphocyte screening and serum cytokine measurements were also performed...
February 15, 2018: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/29455936/engineering-a-clinically-translatable-bioartificial-pancreas-to-treat-type-i-diabetes
#15
REVIEW
Gorka Orive, Dwaine Emerich, Ali Khademhosseini, Shinichi Matsumoto, R M Hernández, J L Pedraz, Tejal Desai, Riccardo Calafiore, Paul de Vos
Encapsulating, or immunoisolating, insulin-secreting cells within implantable, semipermeable membranes is an emerging treatment for type 1 diabetes. This approach can eliminate the need for immunosuppressive drug treatments to prevent transplant rejection and overcome the shortage of donor tissues by utilizing cells derived from allogeneic or xenogeneic sources. Encapsulation device designs are being optimized alongside the development of clinically viable, replenishable, insulin-producing stem cells, for the first time creating the possibility of widespread therapeutic use of this technology...
February 15, 2018: Trends in Biotechnology
https://www.readbyqxmd.com/read/29455927/fibroblast-heterogeneity-and-immunosuppressive-environment-in-human-breast-cancer
#16
Ana Costa, Yann Kieffer, Alix Scholer-Dahirel, Floriane Pelon, Brigitte Bourachot, Melissa Cardon, Philemon Sirven, Ilaria Magagna, Laetitia Fuhrmann, Charles Bernard, Claire Bonneau, Maria Kondratova, Inna Kuperstein, Andrei Zinovyev, Anne-Marie Givel, Maria-Carla Parrini, Vassili Soumelis, Anne Vincent-Salomon, Fatima Mechta-Grigoriou
Carcinoma-associated fibroblasts (CAF) are key players in the tumor microenvironment. Here, we characterize four CAF subsets in breast cancer with distinct properties and levels of activation. Two myofibroblastic subsets (CAF-S1, CAF-S4) accumulate differentially in triple-negative breast cancers (TNBC). CAF-S1 fibroblasts promote an immunosuppressive environment through a multi-step mechanism. By secreting CXCL12, CAF-S1 attracts CD4+ CD25+ T lymphocytes and retains them by OX40L, PD-L2, and JAM2. Moreover, CAF-S1 increases T lymphocyte survival and promotes their differentiation into CD25High FOXP3High , through B7H3, CD73, and DPP4...
February 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29455908/increased-degradation-of-atp-is-driven-by-memory-regulatory-t-cells-in-kidney-transplantation-tolerance
#17
Maxim Durand, Florian Dubois, Cécile Dejou, Eugénie Durand, Richard Danger, Mélanie Chesneau, Carole Brosseau, Pierrick Guerif, Jean-Paul Soulillou, Nicolas Degauque, Jean-François Eliaou, Magali Giral, Nathalie Bonnefoy, Sophie Brouard
Regulatory T cells were recently proposed as the central actor in operational tolerance after renal transplantation. Tolerant patients harbor increased FoxP3hi memory Treg frequency and increased demethylation in the Foxp3 Treg-specific demethylated region when compared to stable kidney recipients and exhibit greater memory Treg suppressive capacities and higher expression of the ectonucleotidase CD39. However, in this particular and unique situation the mechanisms of action of Tregs were not identified. Thus, we analyzed the ability of memory Tregs to degrade extracellular ATP in tolerant patients, healthy volunteers, and patients with stable graft function under immunosuppression and determined the role of immunosuppressive drugs on this process...
February 15, 2018: Kidney International
https://www.readbyqxmd.com/read/29455558/investigational-immunosuppressants-in-early-stage-clinical-trials-for-the-treatment-of-multiple-sclerosis
#18
Alberto Gajofatto, Marco Turatti
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system with an immune mediated pathogenesis. Several therapies that suppress or modulate diverse immune system functions have been used for decades with the aim of modifying the disease course. However, these treatments have either limited efficacy or potentially serious adverse events that prevent first-line use on large scale. Areas covered. The aim of the present article is to review ongoing or recently completed clinical trials investigating immunosuppressive drugs for MS...
February 19, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29455458/diagnosis-presentation-and-initial-severity-of-autoimmune-hepatitis-aih-in-patients-attending-28-hospitals-in-the-uk
#19
Victoria Gordon, Ratul Adhikary, Victoria Appleby, Debasis Das, James Day, Toby Delahooke, Selena Dixon, David Elphick, Claire Hardie, Barbara Hoeroldt, Patricia Hooper, John Hutchinson, Rebecca Jones, Faisal Khan, Guruprasad P Aithal, John McGonigle, Andrew Nelson, Alick Nkhoma, Stavroula Pelitari, Martin Prince, Annell Prosser, Vinay Sathanarayana, Sophia Savva, Naina Shah, Sushma Saksena, Sreedhari Thayalasekaran, Deven Vani, Andrew Yeoman, Dermot Gleeson
BACKGROUND AND AIMS: There is limited information regarding patients with AIH outside relatively few large centres. We describe here the presenting features of patients with AIH, collected as part of an audit involving 28 UK hospitals. METHODS: Patients (incident since 1/1/2007 or prevalent since 1/1/2000) were >18 years and either met 1999 International AIH Group (IAIHG) diagnostic criteria (n=1164), or received immunosuppressive therapy for clinically diagnosed AIH (n=103)...
February 17, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29455288/mycophenolate-mofetil-protects-septic-mice-via-the-dual-inhibition-of-inflammatory-cytokines-and-pd-1
#20
Shun-Wei Huang, Hao Chen, Mei-Ling Lu, Jin-Long Wang, Rong-Li Xie, Bing Zhao, Ying Chen, Zhi-Wei Xu, Jian Fei, En-Qiang Mao, Er-Zhen Chen
Due to the imbalance between hyper-inflammation and hypo-inflammation, which are characterized by excessive cytokine productions and programmed death 1 (PD-1) upregulation, respectively, sepsis remains a highly lethal inflammatory syndrome with limited effective therapies. Mycophenolate mofetil (MMF), an immunosuppressant, has been reported to attenuate various inflammatory diseases. However, the role of MMF in sepsis therapy remains to be elucidated. C57BL-6J mice underwent cecal ligation and puncture (CLP) and were treated either with or without MMF...
February 17, 2018: Inflammation
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