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Immunosuppression

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https://www.readbyqxmd.com/read/29352737/bronchiolitis-obliterans-syndrome-is-associated-with-increased-p-glycoprotein-expression-and-loss-of-glucocorticoid-receptor-from-steroid-resistant-pro-inflammatory-cd8-t-cells
#1
Greg Hodge, Sandra Hodge, Phan Tien Nguyen, Aeneas Yeo, Parama Sarkar, Arash Badiei, C L Holmes-Liew, Paul N Reynolds, Mark Holmes
Immunosuppressive therapy fails to suppress the production of pro-inflammatory cytokines, particularly by CD8+T cells, in stable lung transplant recipients and those undergoing chronic rejection, suggesting that some patients may become relatively resistant to immunosuppressants such as glucocorticoids (GC). We have shown loss of GC receptor (GCR) from the CD8+ cells, and we hypothesized that the drug membrane efflux pump, p-glycoprotein-1 (Pgp), may also be involved in lymphocyte steroid resistance following lung transplant...
January 20, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29352647/ifn-%C3%AE-and-tnf-%C3%AE-pre-licensing-protects-mesenchymal-stromal-cells-from-the-pro-inflammatory-effects-of-palmitate
#2
Lauren Boland, Anthony J Burand, Alex J Brown, Devlin Boyt, Vitor A Lira, James A Ankrum
The use of mesenchymal stromal cell (MSC) therapy for the treatment of type 2 diabetes (T2D) and T2D complications is promising; however, the investigation of MSC function in the setting of T2D has not been thoroughly explored. In our current study, we investigated the phenotype and function of MSCs in a simulated in vitro T2D environment. We show that palmitate, but not glucose, exposure impairs MSC metabolic activity with moderate increases in apoptosis, while drastically affecting proliferation and morphology...
December 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29352516/successful-hematopoietic-cell-transplantation-following-cardiac-transplantation-in-two-pediatric-patients
#3
Rachel Phelan, Angela R Smith, Paul J Orchard, Rebecca K Ameduri
We report two patients who underwent cardiac transplantation at a young age and subsequently required a HCT for varied indications. Despite the challenges associated with HCT following cardiac transplant, including need for altered immunosuppression, toxicities related to chemotherapy exposure, and infection risks, both patients are currently alive and well. There is a paucity of such successful cases documented in the literature, and these cases highlight the critical importance of an experienced, multidisciplinary team when caring for this patient population...
January 19, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29352515/principles-of-alemtuzumab-immunoablation-in-hematopoietic-cell-transplantation-for-non-malignant-diseases-in-children-a-review
#4
REVIEW
Gregory M T Guilcher, Ravi Shah, Shalini Shenoy
Alemtuzumab is a humanized mAb targeted to CD52. Alemtuzumab is highly immunosuppressive with the ability to deplete T and B cells (in addition to other immune cell lines). A growing understanding of the PKs, dosing, and timing of administration of alemtuzumab has allowed for the study of its use as a conditioning agent for allogeneic HCT. The highly immunosuppressive properties of the drug are particularly appealing in the setting of non-malignant HCT, where GVHD provides no clinical benefit and relapse of malignancy is not applicable...
January 19, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29352427/preserved-in-vitro-immunoreactivity-in-children-receiving-long-term-immunosuppressive-therapy-due-to-inflammatory-bowel-disease-or-autoimmune-hepatitis
#5
Teresa Schleker, Eva-Maria Jacobsen, Benjamin Mayer, Gudrun Strauss, Klaus-Michael Debatin, Carsten Posovszky
BACKGROUND: Children with inflammatory bowel disease (IBD) or autoimmune hepatitis (AIH) are at risk for severe infections. This is partially a result of their chronic disease condition but, moreover, a side effect of their immunosuppressive therapy. Currently, vaccinations with live vaccines are regarded as contraindicated under immunosuppressive therapy, mainly because of concerns about side effects and a lack of data showing an adequate immune reaction. As there is no systematic study on the individual immunoreactivity under immunosuppressive therapy in this patient group, we analyzed the lymphocyte subgroups and immunoreactivity of lymphocytes in children with IBD or AIH with and without immunosuppressive therapy in vitro...
January 19, 2018: Molecular and Cellular Pediatrics
https://www.readbyqxmd.com/read/29352246/u-box-ubiquitin-ligase-ppil2-suppresses-breast-cancer-invasion-and-metastasis-by-altering-cell-morphology-and-promoting-snai1-ubiquitination-and-degradation
#6
Zhaojun Jia, Miao Wang, Shujing Li, Xiahui Li, Xiao-Yan Bai, Zhaowei Xu, Yangyang Yang, Bowen Li, Yanan Li, Huijian Wu
Metastasis is the leading cause of breast cancer fatalities. To develop new therapeutic strategies, the mechanisms underlying breast cancer invasion and metastasis need to be further investigated. Peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) is a U-box-type E3 ubiquitin ligase belonging to the cyclophilin family. Proteins within this family are the major cytosolic binding proteins of the immunosuppressant drug cyclosporine A (CsA). Although PPIL2 has been reported to potentially be involved in cell migration, its role in breast cancer is still unclear...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352190/autophagy-promotes-msc-mediated-vascularization-in-cutaneous-wound-healing-via-regulation-of-vegf-secretion
#7
Y An, W J Liu, P Xue, Y Ma, L Q Zhang, B Zhu, M Qi, L Y Li, Y J Zhang, Q T Wang, Y Jin
Vascularization deficiency caused a lot of diseases, such as diabetes ulcer and myocardial infarction. Mesenchymal stem cells (MSCs), with the self-renewal and multipotent differentiation capacities, have been used for many diseases treatment through regulation microenvironment. Numerous studies reported that MSCs transplantation could largely improve cutaneous wound healing via paracrine secretion of growth factors. However, whether MSCs take part in the angiogenesis process directly remains elusive. Previous study proved that autophagy inhibited immunosuppressive function of MSCs and prevented the degradation of MSCs function in inflammatory and senescent microenvironment...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352050/lxr-agonism-depletes-mdscs-to-promote-antitumor-immunity
#8
(no author information available yet)
LXR activation reduces immunosuppressive MDSCs to activate antitumor cytotoxic T cells.
January 19, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29351990/saa3-is-a-key-mediator-of-the-protumorigenic-properties-of-cancer-associated-fibroblasts-in-pancreatic-tumors
#9
Magdolna Djurec, Osvaldo Graña, Albert Lee, Kevin Troulé, Elisa Espinet, Lavinia Cabras, Carolina Navas, María Teresa Blasco, Laura Martín-Díaz, Miranda Burdiel, Jing Li, Zhaoqi Liu, Mireia Vallespinós, Francisco Sanchez-Bueno, Martin R Sprick, Andreas Trumpp, Bruno Sainz, Fátima Al-Shahrour, Raul Rabadan, Carmen Guerra, Mariano Barbacid
Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of abundant desmoplastic stroma primarily composed of cancer-associated fibroblasts (CAFs). It is generally accepted that CAFs stimulate tumor progression and might be implicated in drug resistance and immunosuppression. Here, we have compared the transcriptional profile of PDGFRα+ CAFs isolated from genetically engineered mouse PDAC tumors with that of normal pancreatic fibroblasts to identify genes potentially implicated in their protumorigenic properties...
January 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29351806/isolated-septic-arthritis-of-hip-joint-a-rare-presentation-of-melioidosis-a-case-report
#10
N P Weerasinghe, H M M Herath, T M U Liyanage
BACKGROUND: Despite, Sri Lanka lies in the melioidosis endemic belt between 5°N and 10°N surrounded by countries known to have endemic melioidosis for many years, comparatively fewer cases of melioidosis infection have been reported in Sri Lanka. Melioidosis has a wide spectrum of clinical presentation, ranging from severe pneumonia to abscess formation in various organs. Isolated septic arthritis, which is a rare but well-recognized manifestation of melioidosis, could be the sole presenting problem in some patients with melioidosis...
January 19, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29350834/proton-pump-inhibitors-elevate-infection-rate-in-cardiothoracic-surgery-patients-by-influencing-pmn-function-in-vitro-and-in-vivo
#11
Carolin Maria Haas, Martina Maywald, Andreas Goetzenich, Christian Stoppe, Lothar Rink
Proton-pump inhibitors (PPI) as pantoprazole are highly effective acid suppressive agents that belong to the world's most sold medication. However, they are pronounced to have immunosuppressive aspects. In our study, a negative influence of PPI on functions of polymorphonuclear cells in vitro like phagocytosis, oxidative burst, chemotaxis, and killing activity was shown, whereas formation of neutrophil extracellular traps (NET)osis remained unaffected. Pantoprazole stimulation additionally reduced the production of the proinflammatory cytokine IL-1β in whole blood assay as well as the production of IL-2 and IFN-γ after whole blood stimulation with phytohaemagglutinin...
January 19, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29350748/protective-effect-of-chitosan-oligosaccharides-against-cyclophosphamide-induced-immunosuppression-and-irradiation-injury-in-mice
#12
Xingchen Zhai, Xin Yang, Pan Zou, Yong Shao, Shoujun Yuan, A M Abd El-Aty, Jing Wang
Chitosan oligosaccharides (COS), hydrolyzed products of chitosan, was found to display various biological activities. Herein, we assessed the immunostimulatory activity of COS both in in vitro and in vivo studies. In vitro cytotoxicity studies to murine macrophage RAW264.7 revealed that COS is safe even at the maximum tested concentration of 1000 μg/mL. It also stimulates the production of nitric oxide (NO) and tumor necrosis factor (TNF-α) and enhances the phagocytosis in COS-stimulated RAW264.7. We have shown that the COS could significantly (P < 0...
January 19, 2018: Journal of Food Science
https://www.readbyqxmd.com/read/29350682/conditional-replication-of-oncolytic-viruses-based-on-detection-of-oncogenic-mrna
#13
REVIEW
M Renteln
Recently, split intein-based detection sensors for RNA have been developed that can target custom sequences in a modular fashion. If multi-region, multi-sample sequencing were to be applied to a patient's cancer, truncal (i.e., earliest-occurring) mutations could be identified and could serve as targets for these sense-and-respond modules. The next step would be to utilize an effective vector for treatment. A hyper-virulent herpes simplex virus could possibly serve as this vector, with concurrent immunosuppression to allow for unhindered infection of the tumor regions...
January 19, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29350534/discovery-of-tetrahydroisoquinoline-containing-cxcr4-antagonists-with-improved-in-vitro-admet-properties
#14
Eric J Miller, Edgars Jecs, Valarie M Truax, Brooke M Katzman, Yesim A Tahirovic, Robert J Wilson, Katie M Kuo, Michelle B Kim, Huy H Nguyen, Manohar T Saindane, Huanyu Zhao, Tao Wang, Chi S Sum, Mary Ellen Cvijic, Gretchen M Schroeder, Lawrence J Wilson, Dennis C Liotta
CXCR4 is a 7-transmembrane receptor expressed by hematopoietic stem cells and progeny, as well as by ≥ 48 different cancers types. CXCL12, the only chemokine ligand of CXCR4, is secreted within the tumor microenvironment, providing sanctuary for CXCR4+ tumor cells from immune surveillance and chemotherapeutic elimination by 1) stimulating pro-survival signaling and 2) recruiting CXCR4+ immunosuppressive leukocytes. Additionally, distant CXCL12-rich niches attract and support CXCR4+ metastatic growths. Accordingly, CXCR4 antagonists can potentially obstruct CXCR4-mediated pro-survival signaling, recondition the CXCR4+ leukocyte infiltrate from immunosuppressive to immunoreactive, and inhibit CXCR4+ cancer cell metastasis...
January 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29350416/acute-hemorrhagic-lesions-in-an-immunosuppressed-patient
#15
Irene Salgüero Fernández, Mercedes Sigüenza Sanz, Rita Cabeza Martinez, Fernándo Alfageme Roldan, Laura Nájera Botello, Gastón Roustan Gullón
No abstract text is available yet for this article.
January 19, 2018: International Journal of Dermatology
https://www.readbyqxmd.com/read/29350347/low-birth-weight-is-a-conditioning-factor-for-podocyte-alteration-and-steroid-dependance-in-children-with-nephrotic-syndrome
#16
Giovanni Conti, Dominique De Vivo, Claudia Fede, Stefania Arasi, Angela Alibrandi, Roberto Chimenz, Domenico Santoro
BACKGROUND: Low birth weight (LBW) is associated with reduced nephron endowment. Clinical-pathologic features of post adaptive focal segmental glomerulosclerosis (FSGS) have been observed in subjects with prematurity and very LBW. METHODS: We aimed to investigate the correlation between LBW and outcome in a cohort of 89 children with idiopathic nephrotic syndrome (NS) (2-12 years-old at onset, followed for > 3 years), of whom 21 with LBW (birth weight < 10th percentile for gestational age, gender, ethnicity, and maternal parity or birth weight < 2500 g)...
January 19, 2018: Journal of Nephrology
https://www.readbyqxmd.com/read/29350178/use-of-rifabutin-to-treat-tuberculosis-in-a-cardiac-transplant-recipient-a-case-report%C3%A2
#17
Maya Takayoshi, Kyoichi Wada, Yuka Terada, Sachi Matsuda, Kazuki Nakagita, Akira Oita, Mitsutaka Takada, Aki Shionoiri, Haruki Sunami, Seiko Nakajima, Kensuke Kuroda, Takuma Sato, Osamu Seguchi, Masanobu Yanase, Norihide Fukushima
OBJECTIVE: Tuberculosis is an important concern following organ transplantation. Unfortunately, several antituberculosis drugs interact with immunosuppressants. This report describes our experience with rifabutin (RBT) in the treatment of acute tuberculosis in a cardiac transplant recipient. CASE: A 61-year-old cardiac transplant recipient developed tuberculosis meningitis during treatment of miliary tuberculosis. RBT was given for 27 days concomitantly with cyclosporine (CsA)...
January 19, 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29349774/the-vaccine-adjuvant-alum-promotes-il-10-production-that-suppresses-th1-responses
#18
Ewa Oleszycka, Sean McCluskey, Fiona A Sharp, Natalia Muñoz-Wolf, Emily Hams, Aoife L Gorman, Padraic G Fallon, Ed C Lavelle
The effectiveness of many vaccines licensed for clinical use relates to the induction of neutralising antibodies, facilitated by the inclusion of vaccine adjuvants, particularly alum. However, the ability of alum to preferentially promote humoral rather than cellular, particularly Th1-type responses, is not well understood. We demonstrate that alum activates immunosuppressive mechanisms following vaccination, which limit its capacity to induce Th1 responses. One of the key cytokines limiting excessive immune responses is IL-10...
January 19, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29349763/immune-checkpoint-blockade-for-breast-cancer
#19
April Swoboda, Rita Nanda
An effective antitumor immune response requires interaction between cells of the adaptive and innate immune system. Three key elements are required: generation of activated tumor-directed T cells, infiltration of activated T cells into the tumor microenvironment, and killing of tumor cells by activated T cells. Tumor immune evasion can occur as a result of the disruption of each of these three key T cell activities, resulting in three distinct cancer-immune phenotypes. The immune inflamed phenotype, characterized by the presence of a robust tumor immune infiltrate, suggests impaired activated T cell killing of tumor cells related to the presence of inhibitory factors...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29349658/the-il-10-producing-regulatory-b-cells-b10-cells-and-regulatory-t-cell-subsets-in-neuromyelitis-optica-spectrum-disorder
#20
Eun Bin Cho, Hye-Jin Cho, Jin Myoung Seok, Ju-Hong Min, Eun-Suk Kang, Byoung Joon Kim
B cells contribute to the pathogenesis of neuromyelitis optica (NMO) by producing Aquaporin 4-specific autoantibodies (AQP4-ab); on the other hand, there are certain B cells that suppress immune responses by producing regulatory cytokines, such as IL-10. In this study, we investigated the presence of IL-10-producing Breg cells among lymphocyte subsets. Twenty-two seropositive NMO spectrum disorder (NMOSD) patients (29 samples) and 13 healthy controls (HCs) (14 samples) were enrolled. All NMOSD patients have received one or more immunosuppressive drugs...
January 19, 2018: Neurological Sciences
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