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https://www.readbyqxmd.com/read/28212655/elderly-onset-hereditary-pulmonary-alveolar-proteinosis-and-its-cytokine-profile
#1
Masayuki Ito, Kazuyuki Nakagome, Hiromitsu Ohta, Keiichi Akasaka, Yoshitaka Uchida, Atsushi Hashimoto, Ayako Shiono, Toshinori Takada, Makoto Nagata, Jun Tohyama, Koichi Hagiwara, Minoru Kanazawa, Koh Nakata, Ryushi Tazawa
BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by surfactant accumulation, and is caused by disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. Abnormalities in CSF2 receptor alpha (CSF2RA) were reported to cause pediatric hereditary PAP. We report here the first case of CSF2RA-mutated, elderly-onset hereditary (h) PAP. CASE PRESENTATION: The patient developed dyspnea on exertion, and was diagnosed with PAP at the age of 77 years, based on findings from chest computed tomography scan and bronchoalveolar lavage...
February 17, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28212528/the-crispr-cas9%C3%A2-system-efficiently-reverts-the-tumorigenic-ability-of-bcr-abl-in-vitro-and-in-a-xenograft-model-of-chronic-myeloid-leukemia
#2
Ignacio García-Tuñón, María Hernández-Sánchez, José Luis Ordoñez, Veronica Alonso-Pérez, Miguel Álamo-Quijada, Rocio Benito, Carmen Guerrero, Jesús María Hernández-Rivas, Manuel Sánchez-Martín
CRISPR/Cas9 technology was used to abrogate p210 oncoprotein expression in the Boff-p210 cell line, a pro-B line derived from interlukin-3-dependent Baf/3, that shows IL-3-independence arising from the constitutive expression of BCR-ABL p210. Using this approach, pools of Boff-p210-edited cells and single edited cell-derived clones were obtained and functionally studied in vitro. The loss of p210 expression in Boff-p210 cells resulted in the loss of ability to grow in the absence of IL-3, as the Baf/3 parental line, showing significantly increased apoptosis levels...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28208123/analysis-of-acquired-mutations-in-transgenes-arising-in-ba-f3-transformation-assays-findings-and-recommendations
#3
Kevin Watanabe-Smith, Jamila Godil, Anupriya Agarwal, Cristina Tognon, Brian Druker
The identification and functional validation of potentially oncogenic mutations in leukemia is an essential step toward a future of personalized targeted therapy. To assess the oncogenic capacity of individual mutations, reliable and scalable in vitro experimental approaches are required. Since 1988, researchers have used the IL-3 dependent Ba/F3 transformation assay to validate the oncogenic potential of mutations to drive factor-independent growth. Here we report a previously unrecognized phenomenon whereby Ba/F3 cells, engineered to express weakly transforming mutations, present with additional acquired mutations in the expressed transgene following factor withdrawal...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28193842/experimental-arthritis-is-dependent-on-mouse-mast-cell-protease-5
#4
Richard L Stevens, H Patrick McNeil, Lislaine A Wensing, Kichul Shin, G William Wong, Philip M Hansbro, Steven A Krilis
The constitutive heparin+ (HP) mast cells (MCs) in mice express mouse MC protease (mMCP)-5 and carboxypeptidase A (mMC CPA). The amino acid sequence of mMCP-5 is most similar to that of human chymase-1, as is the nucleotide sequences of their genes and transcripts. Using a homologous recombination approach, a C57BL/6 mouse line was created that possessed a disrupted mMCP-5 gene. The resulting mice were fertile and had no obvious developmental abnormality. Lack of mMCP-5 protein did not alter the granulation of the IL-3/IL-9-dependent mMCP 2+ MCs in the jejunal mucosa of Trichinella spiralis-infected mice...
February 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28146632/antibody-targeted-cyclodextrin-based-nanoparticles-for-sirna-delivery-in-the-treatment-of-acute-myeloid-leukemia-physicochemical-characteristics-in-vitro-mechanistic-studies-and-ex-vivo-patient-derived-therapeutic-efficacy
#5
Jianfeng Guo, Eileen G Russell, Raphael Darcy, Thomas G Cotter, Sharon L McKenna, Mary R Cahill, Caitriona M O'Driscoll
Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and is associated with high relapse rates. It is known that leukemia stem cells (LSCs), a very small subpopulation of the total number of leukemic cells, maintain the leukemia phenotype (∼80-90% of AML remain the same as at first diagnosis), display chemotherapy resistance, and contribute to disease regeneration. Therefore, targeting LSCs could control the relapse of AML. Small interfering RNA (siRNA), an effector of the RNA interference (RNAi) pathway, can selectively downregulate any gene implicated in the pathology of disease, presenting great potential for treatment of AML...
February 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28112181/il-3-and-ctla4-gene-polymorphisms-may-influence-the-tacrolimus-dose-requirement-in-chinese-kidney-transplant-recipients
#6
Mou-Ze Liu, Hai-Yan He, Yue-Li Zhang, Yong-Fang Hu, Fa-Zhong He, Jian-Quan Luo, Zhi-Ying Luo, Xiao-Ping Chen, Zhao-Qian Liu, Hong-Hao Zhou, Ming-Jie Shao, Ying-Zi Ming, Hua-Wen Xin, Wei Zhang
The highly variable pharmacokinetics and narrow therapeutic window of tacrolimus (TAC) has hampered its clinical use. Genetic polymorphisms may contribute to the variable response, but the evidence is not compelling, and the explanation is unclear. In this study we attempted to find previously unknown genetic factors that may influence the TAC dose requirements. The association of 105 pathway-related single nucleotide polymorphisms (SNPs) with TAC dose-adjusted concentrations (C0/D) was examined at 7, 30 and 90 d post-operation in 382 Chinese kidney transplant recipients...
January 23, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28108746/myeloid-derived-suppressor-cells-can-be-efficiently-generated-from-human-hematopoietic-progenitors-and-peripheral-blood-monocytes
#7
Sílvia Casacuberta-Serra, Marta Parés, Arantxa Golbano, Elisabet Coves, Carmen Espejo, Jordi Barquinero
Myeloid-derived suppressor cells (MDSCs) play an important role in controlling inflammation. As such, they are both a therapeutic target and, based on the administration of ex-vivo-generated MDSCs, a therapeutic tool. However, there are relatively few reports describing methods to generate human MDSCs, and most of them rely on cells obtained from peripheral blood monocytes. We investigated alternative approaches to the generation of MDSCs from hematopoietic progenitors and monocytes. Purified CD34(+) hematopoietic progenitors from apheresis products and CD14(+) cells isolated from buffy coats were cultured in the presence of different combinations of cytokines...
January 21, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28096423/trogocytosis-of-peptide-mhc-class-ii-complexes-from-dendritic-cells-confers-antigen-presenting-ability-on-basophils
#8
Kensuke Miyake, Nozomu Shiozawa, Toshihisa Nagao, Soichiro Yoshikawa, Yoshinori Yamanishi, Hajime Karasuyama
Th2 immunity plays important roles in both protective and allergic responses. Nevertheless, the nature of antigen-presenting cells responsible for Th2 cell differentiation remains ill-defined compared with the nature of the cells responsible for Th1 and Th17 cell differentiation. Basophils have attracted attention as a producer of Th2-inducing cytokine IL-4, whereas their MHC class II (MHC-II) expression and function as antigen-presenting cells are matters of considerable controversy. Here we revisited the MHC-II expression on basophils and explored its functional relevance in Th2 cell differentiation...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096272/anti-leukemia-efficacy-and-mechanisms-of-action-of-sl-101-a-novel-anti-cd123-antibody-conjugate-in-acute-myeloid-leukemia
#9
Lina Han, Jeffrey L Jorgensen, Christopher Brooks, Ce Shi, Qi Zhang, Graciela M Nogueras González, Antonio Cavazos, Rongqing Pan, Hong Mu, Sa Wang, Jin Zhou, Gheath Alatrash, Stefan O Ciurea, Michael Rettig, John F DiPersio, Jorge E Cortes, Xuelin Huang, Hagop Kantarjian, Michael Andreeff, Farhad Ravandi-Kashani, Marina Konopleva
PURPOSE: The persistence of leukemia stem cells (LSC)-containing cells after induction therapy may contribute to minimal residual disease (MRD) and relapse in acute myeloid leukemia (AML). We investigated the clinical relevance of CD34+CD123+ LSC-containing cells and anti-leukemia potency of a novel antibody-conjugate SL-101 in targeting CD123+ LSCs. Experimental Methods and Results: In a retrospective study on 86 newly diagnosed AML patients, we demonstrated that a higher proportion of CD34+CD123+ LSC-containing cells in remission was associated with persistent MRD, and predicted shorter relapse-free survival in patients with poor-risk cytogenetics...
January 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28053519/network-pharmacology-based-identification-of-key-pharmacological-pathways-of-yin-huang-qing-fei-capsule-acting-on-chronic-bronchitis
#10
Guohua Yu, Yanqiong Zhang, Weiqiong Ren, Ling Dong, Junfang Li, Ya Geng, Yi Zhang, Defeng Li, Haiyu Xu, Hongjun Yang
For decades in China, the Yin-Huang-Qing-Fei capsule (YHQFC) has been widely used in the treatment of chronic bronchitis, with good curative effects. Owing to the complexity of traditional Chinese herbal formulas, the pharmacological mechanism of YHQFC remains unclear. To address this problem, a network pharmacology-based strategy was proposed in this study. At first, the putative target profile of YHQFC was predicted using MedChem Studio, based on structural and functional similarities of all available YHQFC components to the known drugs obtained from the DrugBank database...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28044192/porcine-mast-cells-infected-with-h1n1-influenza-virus-release-histamine-and-inflammatory-cytokines-and-chemokines
#11
In Hong Lee, Hyun Soo Kim, Sang Heui Seo
Mast cells reside in many tissues, including the lungs, and might play a role in enhancing influenza virus infections in animals. In this study, we cultured porcine mast cells from porcine bone marrow cells with IL-3 and stem cell factor to study the infectivity and activation of the 2009 pandemic H1N1 influenza virus of swine origin. Porcine mast cells were infected with H1N1 influenza virus, without the subsequent production of infectious viruses but were activated, as indicated by the release of histamines...
January 2, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28039843/il-3-and-gm-csf-modulate-functions-of-splenic-macrophages-in-enu-induced-leukemia
#12
Ashish Kumar Singha, Bhaskar Bhattacharjee, Bhaskar Saha, Debasish Maiti
Leukemia is often accompanied by enhanced susceptibility to infection due to compromised B cell and T cell functions. The alterations in macrophage functions in leukemia remain less investigated. Herein, we examined macrophages for their functions and responsiveness to IL-3 and GM-CSF in ENU-induced leukemia in BALB/c mice. We observed that the macrophages from the leukemic mice had less phagocytic activity, reduced chemotactic activity in response to monocyte chemoattractant protein-1(MCP-1), and decreased expression of iNOS, GM-CSF, TLR2, TLR4, IFN-γ and TNF-α...
December 28, 2016: Cytokine
https://www.readbyqxmd.com/read/28038963/phosphorylated-cis-suppresses-the-epo-or-jak2-v617f-mutant-triggered-cell-proliferation-through-binding-to-epor
#13
Megumi Funakoshi-Tago, Takuro Moriwaki, Fumihito Ueda, Hiroomi Tamura, Tadashi Kasahara, Kenji Tago
The JAK2 V617F mutant-mediated aberrant signaling pathway is a hallmark of myeloproliferative neoplasms (MPNs). Although cytokine-inducible Src homology 2 protein (CIS) and suppressors of cytokine signaling (SOCS) are negative regulators of the JAK-STAT pathway, the functional role of CIS/SOCS family members in the JAK2 V617F mutant-induced oncogenic signaling pathway has not yet been elucidated. In this study, we found that the expression of CIS and SOCS1 was induced through the activation of signal transducer and activator of transcription 5 (STAT5) in not only the cells stimulated with Epo or IL-3 but also the cells transformed by the JAK2 V617F mutant...
February 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28036233/shared-and-distinct-aspects-of-the-sepsis-transcriptomic-response-to-fecal-peritonitis-and-pneumonia
#14
Katie L Burnham, Emma E Davenport, Jayachandran Radhakrishnan, Peter Humburg, Anthony C Gordon, Paula Hutton, Eduardo Svoren-Jabalera, Christopher Garrard, Adrian Vs Hill, Charles J Hinds, Julian C Knight
RATIONALE: Heterogeneity in the septic response has hindered efforts to understand pathophysiology and develop targeted therapies. Source of infection, with different causative organisms and temporal changes, might influence this heterogeneity. OBJECTIVES: To investigate individual and temporal variation in the transcriptomic response to sepsis due to fecal peritonitis, and to compare with community acquired pneumonia. METHODS: We performed genome-wide gene expression profiling in peripheral blood leukocytes for adult patients admitted to intensive care with sepsis due to fecal peritonitis (n=117) or community acquired pneumonia (n=126), and non-septic controls (n=10)...
December 30, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28031576/anti-colony-stimulating-factor-therapies-for-inflammatory-and-autoimmune-diseases
#15
REVIEW
John A Hamilton, Andrew D Cook, Paul P Tak
Granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF; also known as CSF1), granulocyte colony-stimulating factor (G-CSF) and interleukin-3 (IL-3) can each play a part in the host response to injury and infection, and there is burgeoning interest in targeting these CSFs in inflammatory and autoimmune disorders, as well as in cancer. For success in clinical medicine, therapeutic targeting will need to be delineated from current strategies. The individual CSFs have unique biological roles, suggesting that they could be used to target specific conditions...
29, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28000952/human-basophils-are-a-soucre-of-and-are-differentially-activated-by-il-31
#16
U Raap, M Gehring, S Kleiner, U Rüdrich, B Eiz-Vesper, H Haas, A Kapp, B F Gibbs
BACKGROUND: Basophils are important effector cells involved in the pathogenesis of inflammatory skin diseases including chronic urticaria which is associated by increased IL-31 serum levels. So far the effects of IL-31 on human basophils are unknown. OBJECTIVE: To analyse the functional role of IL-31 in basophil biology. METHODS: IL-31 expression was evaluated in skin samples derived from chronic spontaneous urticaria patients. Oncostatin M receptor (OSMR), IL-31 receptor A (RA) and IL-31 protein expressions were analysed on human basophils from healthy donors...
December 21, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28000949/il-3-up-regulates-and-activates-human-eosinophil-cd32-and-%C3%AE-m%C3%AE-2-integrin-causing-degranulation
#17
S Esnault, M W Johansson, E A Kelly, L Koenderman, D F Mosher, N N Jarjour
BACKGROUND: Eosinophils contribute to the pathogenesis of multiple diseases, including asthma. Treatment with antibodies targeting IL-5 or IL-5 receptor α reduces the frequency of asthma exacerbations. Eosinophil receptors for IL-5 share a common ß-chain with IL-3 and GM-CSF receptors. We recently reported that IL-3 is more potent than IL-5 or GM-CSF in maintaining the ERK/p90S6K/RPS6 ribosome-directed signaling pathway, leading to increased protein translation. OBJECTIVE: We aimed to determine disease-relevant consequences of prolonged eosinophil stimulation with IL-3...
December 21, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27999422/plasma-intermedin-level-indicates-severity-and-treatment-efficacy-of-septic-shock-in-sprague-dawley-sd-rats
#18
Su-Xian Yang, Yun-Xiu Chen, Jing Xu, Zhao-Hui Yang
BACKGROUND The aim of this study was to investigate the value of plasma intermedin (IMD) in assessing severity and treatment efficacy of septic shock. MATERIAL AND METHODS Healthy male Sprague-Dawley (SD) rats were chosen and divided into a normal control group (n=15) and a shock model group (n=27) that received intravenous injection of lipopolysaccharide (LPS). Then, 3 specimens were taken from each group. The shock model group rats were divided into an LPS group and a treatment group with 12 rats each. The treatment group received intravenous injection of compound sodium lactate solution...
December 21, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27980777/improved-b-cell-development-in-humanized-nod-scid-il2r%C3%AE-null-mice-transgenically-expressing-human-stem-cell-factor-granulocyte-macrophage-colony-stimulating-factor-and-interleukin-3
#19
Sonal Jangalwe, Leonard D Shultz, Anuja Mathew, Michael A Brehm
INTRODUCTION: Immunodeficient mice engrafted with human immune systems support studies of human hematopoiesis and the immune response to human-specific pathogens. A significant limitation of these humanized mouse models is, however, a severely restricted ability of human B cells to undergo class switching and produce antigen-specific IgG after infection or immunization. METHODS: In this study, we have characterized the development and function of human B cells in NOD-scid IL2Rγ(null) (NSG) mice transgenically expressing human stem cell factor (SCF), granulocyte macrophage colony-stimulating factor (GM-CSF), and IL-3 (NSG-SGM3) following engraftment with human hematopoietic stem cells, autologous fetal liver, and thymic tissues (bone marrow, liver, thymus or BLT model)...
December 2016: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/27935258/polyphenols-from-lonicera-caerulea-l-berry-attenuate-experimental-nonalcoholic-steatohepatitis-by-inhibiting-proinflammatory-cytokines-productions-and-lipid-peroxidation
#20
Shusong Wu, Satoshi Yano, Ayami Hisanaga, Xi He, Jianhua He, Kozue Sakao, De-Xing Hou
SCOPE: Nonalcoholic steatohepatitis (NASH) is a common disease, which is closely associated with inflammation and oxidative stress, and Lonicera caerulea L. polyphenols (LCP) are reported to possess both antioxidant and anti-inflammatory properties. This study aimed to investigate the protective effects and mechanisms of LCP on NASH in a high-fat diet plus carbon tetrachloride (CCL4 ) induced mouse model. METHODS AND RESULTS: Mice were fed with high-fat diet containing LCP (0...
December 9, 2016: Molecular Nutrition & Food Research
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