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https://www.readbyqxmd.com/read/28641141/rag2-involves-the-ig%C3%AE%C2%BA-locus-demethylation-during-b-cell-development
#1
Caijun Wu, Yanying Dong, Xiaohui Zhao, Ping Zhang, Mingzhe Zheng, Hua Zhang, Shichang Li, Yaofeng Jin, Yunfeng Ma, Huixun Ren, Yanhong Ji
The genes encoding the immunoglobulin κ light chain are assembled during B cell development by V(D)J recombination. For efficient rearrangement, the Igκ locus must undergo a series of epigenetic changes. One such epigenetic mark is DNA methylation. The mechanism that the Igκ locus is selectively demethylated at the pre-B cell stage has not previously been characterized. Here, we employed bisulfite DNA-modification assays to analyze the methylation status of the Igκ locus in primary pre-B cells from RAG-deficient mice with pre-rearranged Igh knock-in allele...
June 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28636758/fetal-overnutrition-and-offspring-insulin-resistance-and-%C3%AE-cell-function-the-exploring-perinatal-outcomes-among-children-epoch-study
#2
K A Sauder, C W Hockett, B M Ringham, D H Glueck, D Dabelea
AIMS: To examine the associations of intrauterine exposure to maternal diabetes and obesity with offspring insulin resistance, β-cell function and oral disposition index in a longitudinal observational study of ethnically diverse offspring. METHODS: A total of 445 offspring who were exposed (n=81) or not exposed (n=364) to maternal diabetes in utero completed two fasting blood measurements at mean (sd) ages of 10.5 (1.5) and 16.5 (1.2) years, respectively, and an oral glucose tolerance test at the second visit...
June 21, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/28635557/cellular-immune-responses-of-older-adults-to-four-influenza-vaccines-results-of-a-randomized-controlled-comparison
#3
Arun Kumar, Janet E McElhaney, Lisa Walrond, Terry D Cyr, Shahzma Merani, Tobias R Kollmann, Scott A Halperin, David W Scheifele
Cellular immunity is important for protection against the serious complications of influenza in older adults. As it is unclear if newer influenza vaccines elicit greater cellular responses than standard vaccines, we compared responses to two standard and two newer licensed trivalent inactivated vaccines (TIVs) in a randomized trial in older adults. Non-frail adults ≥65 years old were randomly assigned to receive standard subunit, MF59-adjuvanted subunit, standard split-virus or intradermal split-virus TIV...
June 21, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28632322/reduced-intensity-conditioning-allogeneic-transplantation-after-salvage-treatment-with-dt-pace-in-myeloma-patients-relapsing-early-after-autologous-transplant
#4
K Randall, M Kaparou, E Xenou, S Paneesha, B Kishore, A Kanellopoulos, R Lovell, K Holder, J Suhr, L Baker, L Ryan, E Nikolousis
OBJECTIVE: In this retrospective single center study we have looked into the transplant outcomes(overall survival OS, progression free survival PFS,GvHD) and the role of chimerism, DLI and pre-transplant characteristics in patients who had a suboptimal response (<12 months)to an autologous stem cell transplant for myeloma and underwent an Alemtuzumab T-cell depleted reduced intensity allograft(RIC). METHODS: 24 patients were salvaged with 2 cycles of DT-PACE and received a RIC transplant with Fludarabine, Melphalan and Alemtuzumab...
June 20, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28631160/role-of-imaging-in-the-follow-up-of-t2-t3-glottic-cancer-treated-by-transoral-laser-microsurgery
#5
Filippo Marchi, Cesare Piazza, Marco Ravanelli, Giovanna Gaggero, Giampiero Parrinello, Alberto Paderno, Pietro Perotti, Marta Filauro, Roberto Maroldi, Giorgio Peretti
An unblinded retrospective analysis of prospectively collected data was carried out on 138 patients affected by glottic pT2 and selected pT3 squamous cell carcinomas (SCC) treated by transoral laser microsurgery (TLM). The entire cohort was divided into two groups: Group A included 78 "high-risk" patients (pT2 with impaired vocal cord mobility, pT3 for anterior paraglottic and/or pre-epiglottic space invasion, presence of angioembolization, perineural spread, and positive lymph nodes in the neck) who underwent postoperative surveillance by endoscopy and imaging (CT or MR), while Group B included 60 "low-risk" patients (pT2 with absence of the above-mentioned features) who underwent endoscopic follow-up alone...
June 19, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28628994/tio2-surfaces-support-neuron-growth-during-electric-field-stimulation
#6
M Canillas, B Moreno, E Chinarro, A M Rajnicek
TiO2 is proposed here for the first time as a substrate for neural prostheses that involve electrical stimulation. Several characteristics make TiO2 an attractive material: Its electrochemical behaviour as an insulator prevents surface changes during stimulation. Hydration creates -OH groups at the surface, which aid cell adhesion by interaction with inorganic ions and macromolecules in cell membranes. Its ability to neutralize reactive oxygen and nitrogen species that trigger inflammatory processes confers biocompatibility properties in dark conditions...
October 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28628091/the-btg2-prmt1-module-limits-pre-b-cell-expansion-by-regulating-the-cdk4-cyclin-d3-complex
#7
Elmar Dolezal, Simona Infantino, Friedel Drepper, Theresa Börsig, Aparajita Singh, Thomas Wossning, Gina J Fiala, Susana Minguet, Bettina Warscheid, David M Tarlinton, Hassan Jumaa, David Medgyesi, Michael Reth
Developing pre-B cells in the bone marrow alternate between proliferation and differentiation phases. We found that protein arginine methyl transferase 1 (PRMT1) and B cell translocation gene 2 (BTG2) are critical components of the pre-B cell differentiation program. The BTG2-PRMT1 module induced a cell-cycle arrest of pre-B cells that was accompanied by re-expression of Rag1 and Rag2 and the onset of immunoglobulin light chain gene rearrangements. We found that PRMT1 methylated cyclin-dependent kinase 4 (CDK4), thereby preventing the formation of a CDK4-Cyclin-D3 complex and cell cycle progression...
June 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28628088/an-individualised-risk-adapted-protocol-of-pre-and-post-transplant-zoledronic-acid-reduces-bone-loss-after-allogeneic-stem-cell-transplantation-results-of-a-phase-ii-prospective-trial
#8
A Grigg, B Butcher, B Khodr, A Bajel, M Hertzberg, S Patil, A B D'Souza, P Ganly, P Ebeling, E Wong
Bone loss occurs frequently following allogeneic haematopoietic stem cell transplantation (alloSCT). The Australasian Leukaemia and Lymphoma Group conducted a prospective phase II study of pretransplant zoledronic acid (ZA) and individualised post-transplant ZA to prevent bone loss in alloSCT recipients. Patients received ZA 4 mg before conditioning. Administration of post-transplant ZA from days 100 to 365 post alloSCT was determined by a risk-adapted algorithm based on serial bone density assessments and glucocorticoid exposure...
June 19, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28627620/protective-effect-of-human-serum-amyloid-p-on-ccl4-induced-acute-liver-injury-in-mice
#9
Min Cong, Weihua Zhao, Tianhui Liu, Ping Wang, Xu Fan, Qingling Zhai, Xiaoli Bao, Dong Zhang, Hong You, Tatiana Kisseleva, David A Brenner, Jidong Jia, Hui Zhuang
Human serum amyloid P (hSAP), a member of the pentraxin family, inhibits the activation of fibrocytes in culture and inhibits experimental renal, lung, skin and cardiac fibrosis. As hepatic inflammation is one of the causes of liver fibrosis, in the present study, we investigated the hepatoprotective effects of hSAP against carbon tetrachloride (CCl4)-induced liver injury. Our data indicated that hSAP attenuated hepatic histopathological abnormalities and significantly decreased inflammatory cell infiltration and pro-inflammatory factor expression...
June 14, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28624612/human-mast-cells-present-antigen-to-autologous-cd4-t-cells
#10
Sahar Lotfi-Emran, Brant R Ward, Quang T Le, Andrea L Pozez, Masoud H Manjili, Judith Woodfolk, Lawrence B Schwartz
BACKGROUND: Mast cells (MCs), the primary effector cell of the atopic response, participate in immune defense at host/environment interfaces, yet the mechanisms by which they interact with CD4(+)-T cells has been controversial. OBJECTIVE: We utilize in situ-matured primary human MCs and matched CD4(+)-T cells to diligently assess the ability of MCs to act as antigen-presenting cells. METHODS: We examined mature human skin-derived MCs by flow cytometry for expression of antigen-presenting molecules; for their ability to stimulate CD4(+)-T cells to express CD25 and proliferate when exposed to superantigen or to CMV antigen using matched T cells and MCs from CMV seropositive or seronegative donors; and for uptake of antigens...
June 14, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28622539/features-of-amygdala-in-patients-with-mesial-temporal-lobe-epilepsy-and-hippocampal-sclerosis-an-mri-volumetric-and-histopathological-study
#11
Yoko Nakayama, Hiroshi Masuda, Hiroshi Shirozu, Yosuke Ito, Takefumi Higashijima, Hiroki Kitaura, Yukihiko Fujii, Akiyoshi Kakita, Masafumi Fukuda
OBJECTIVE: It is well-known that there is a correlation between the neuropathological grade of hippocampal sclerosis (HS) and neuroradiological atrophy of the hippocampus in mesial temporal lobe epilepsy (mTLE) patients. However, there is no strict definition or criterion regarding neuron loss and atrophy of the amygdala neighboring the hippocampus. We examined the relationship between HS and neuronal loss in the amygdala. MATERIALS AND METHODS: Nineteen mTLE patients with neuropathological proof of HS were assigned to Group A, while seven mTLE patients without HS were assigned to Group B...
May 22, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28621839/evaluation-of-hemodynamic-performance-of-a-combined-ecls-and-crrt-circuit-in-seven-positions-with-a-simulated-neonatal-patient
#12
Elizabeth Profeta, Kaitlyn Shank, Shigang Wang, Christian O'Connor, Allen R Kunselman, Karl Woitas, John L Myers, Akif Ündar
As it is common for patients treated with extracorporeal life support (ECLS) to subsequently require continuous renal replacement therapy (CRRT), and neonatal patients encounter limitations due to lack of access points, inclusion of CRRT in the ECLS circuit could provide advanced treatment for this population. The objective of this study was to evaluate an alternative neonatal ECLS circuit containing either a Maquet RotaFlow centrifugal pump or Maquet HL20 roller pump with one of seven configurations of CRRT using the Prismaflex 2000 System...
June 16, 2017: Artificial Organs
https://www.readbyqxmd.com/read/28620394/vitamin-d-counteracts-mycobacterium-tuberculosis-induced-cathelicidin-downregulation-in-dendritic-cells-and-allows-th1-differentiation-and-ifn%C3%AE-secretion
#13
Anna K O Rode, Martin Kongsbak, Marie M Hansen, Daniel Villalba Lopez, Trine B Levring, Anders Woetmann, Niels Ødum, Charlotte M Bonefeld, Carsten Geisler
Tuberculosis (TB) presents a serious health problem with approximately one-third of the world's population infected with Mycobacterium tuberculosis in a latent state. Experience from the pre-antibiotic era and more recent clinical studies have established a beneficial role of sunlight and vitamin D in patients with TB. At the same time, experimental data have shown that Th1 cells through production of IFNγ are crucial for cathelicidin release by macrophages, bacterial killing, and containment of M. tuberculosis in granulomas...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28620384/measuring-leukocyte-adhesion-to-primary-endothelial-cells-after-photon-and-charged-particle-exposure-with-a-dedicated-laminar-flow-chamber
#14
Nadine Erbeldinger, Felicitas Rapp, Svetlana Ktitareva, Philipp Wendel, Anna S Bothe, Till Dettmering, Marco Durante, Thomas Friedrich, Bianca Bertulat, Stephanie Meyer, M C Cardoso, Stephanie Hehlgans, Franz Rödel, Claudia Fournier
The vascular endothelium interacts with all types of blood cells and is a key modulator of local and systemic inflammatory processes, for example, in the adhesion of blood leukocytes to endothelial cells (EC) and the following extravasation into the injured tissue. The endothelium is constantly exposed to mechanical forces caused by blood flow, and the resulting shear stress is essential for the maintenance of endothelial function. Changes in local hemodynamics are sensed by EC, leading to acute or persistent changes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28618941/molecular-interplay-of-pro-inflammatory-transcription-factors-and-non-coding-rnas-in-esophageal-squamous-cell-carcinoma
#15
REVIEW
Gopinath M Sundaram, Pallaval Veera Bramhachari
Esophageal squamous cell carcinoma is the sixth most common cancer in the developing world. The aggressive nature of esophageal squamous cell carcinoma, its tendency for relapse, and the poor survival prospects of patients diagnosed at advanced stages, represent a pressing need for the development of new therapies for this disease. Chronic inflammation is known to have a causal link to cancer pre-disposition. Nuclear factor kappa B and signal transducer and activator of transcription 3 are transcription factors which regulate immunity and inflammation and are emerging as key regulators of tumor initiation, progression, and metastasis...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28616701/predictive-value-of-pd-l1-based-on-mrna-level-in-the-treatment-of-stage-iv-melanoma-with-ipilimumab
#16
C Brüggemann, M C Kirchberger, S M Goldinger, B Weide, A Konrad, M Erdmann, D Schadendorf, R S Croner, L Krähenbühl, K C Kähler, C Hafner, W Leisgang, F Kiesewetter, R Dummer, G Schuler, M Stürzl, L Heinzerling
INTRODUCTION: PD-L1 is established as a predictive marker for therapy of non-small cell lung cancer with pembrolizumab. Furthermore, PD-L1 positive melanoma has shown more favorable outcomes when treated with anti-PD1 antibodies and dacarbazine compared to PD-L1 negative melanoma. However, the role of PD-L1 expression with regard to response to checkpoint inhibition with anti-CTLA-4 is not clear, yet. In addition, the lack of standardization in the immunohistochemical assessment of PD-L1 makes the comparison of results difficult...
June 14, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28615926/mechanistic-modelling-of-drug-induced-liver-injury-investigating-the-role-of-innate-immune-responses
#17
Lisl Km Shoda, Christina Battista, Scott Q Siler, David S Pisetsky, Paul B Watkins, Brett A Howell
Drug-induced liver injury (DILI) remains an adverse event of significant concern for drug development and marketed drugs, and the field would benefit from better tools to identify liver liabilities early in development and/or to mitigate potential DILI risk in otherwise promising drugs. DILIsym software takes a quantitative systems toxicology approach to represent DILI in pre-clinical species and in humans for the mechanistic investigation of liver toxicity. In addition to multiple intrinsic mechanisms of hepatocyte toxicity (ie, oxidative stress, bile acid accumulation, mitochondrial dysfunction), DILIsym includes the interaction between hepatocytes and cells of the innate immune response in the amplification of liver injury and in liver regeneration...
2017: Gene Regulation and Systems Biology
https://www.readbyqxmd.com/read/28615446/lysosome-mediated-degradation-of-a-distinct-pool-of-lipid-droplets-during-hepatic-stellate-cell-activation
#18
Maidina Tuohetahuntila, Martijn R Molenaar, Bart Spee, Jos F Brouwers, Richard Wubbolts, Martin Houweling, Cong Yan, Hong Du, Brian C VanderVen, Arie B Vaandrager, J Bernd Helms
Activation of hepatic stellate cells (HSCs) is a critical step in the development of liver fibrosis. During activation, HSCs lose their lipid droplets (LDs) containing triacylglycerols (TAGs), cholesteryl esters (CEs) and retinyl esters (REs). We previously provided evidence for the presence of two distinct LD pools, a pre-existing and a dynamic LD pool. Here we investigate the mechanisms of neutral lipid metabolism in the pre-existing LD pool. To investigate the involvement of lysosomal degradation of neutral lipids, we studied the effect of lalistat, a specific lysosomal acid lipase (LAL/Lipa) inhibitor on LD degradation in HSCs during activation in vitro The LAL-inhibitor increased the levels of TAG, CE and RE in both rat and mouse HSCs...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28615039/interleukin-21-promotes-thymopoiesis-recovery-following-hematopoietic-stem-cell-transplantation
#19
Aurélie Tormo, Fatemeh Khodayarian, Yun Cui, Edouard Al-Chami, Reem Kanjarawi, Beatriz Noé, Huijie Wang, Moutih Rafei
BACKGROUND: Impaired T cell reconstitution remains a major deterrent in the field of bone marrow (BM) transplantation (BMT) due to pre-conditioning-induced damages inflicted to the thymi of recipient hosts. Given the previously reported thymo-stimulatory property of interleukin (IL)-21, we reasoned that its use post-BMT could have a profound effect on de novo T cell development. METHODS: To evaluate the effect of IL-21 on de novo T cell development in vivo, BM derived from RAG2p-GFP mice was transplanted into LP/J mice...
June 14, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28614765/drug-delivery-systems-improving-chemical-and-physical-properties-of-anticancer-drugs-currently-investigated-for-treatment-of-solid-tumors
#20
R Aleksandrowicz, B Taciak, M Krol
Cancer is the second leading cause of death worldwide. Conventional cancer treatment like chemotherapy do not fulfil the expectations of both patients and physicians and there is a pressing need for a new kind of therapies that will increase drug delivery to the tumor mass. Standard chemotherapy does not show either specific tumor-targeting, or selective mode of action for cancer cells. Moreover, tumor microenvironments additionally disturb drug perfusion and diffusion. Currently approved anticancer drugs have many limitations and therefore special delivery systems improving their chemical and physical properties are beneficial...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
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