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macrophagic activation syndrome

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https://www.readbyqxmd.com/read/28323963/an-antibody-to-notch2-reverses-the-osteopenic-phenotype-of-hajdu-cheney-mutant-male-mice
#1
Ernesto Canalis, Archana Sanjay, Jungeun Yu, Stefano Zanotti
Notch receptors play a central role in skeletal development and bone remodeling. Hajdu Cheney Syndrome (HCS), a disease characterized by osteoporosis and fractures, is associated with gain-of-NOTCH2 function mutations. To study HCS, we created a mouse model harboring a point 6955C>T mutation in the Notch2 locus upstream of the proline (P), glutamic acid (E), serine (S) and threonine (T) domain leading to a Q2319X change at the amino acid level. Notch2Q2319X heterozygous mutants exhibited cancellous and cortical bone osteopenia...
January 31, 2017: Endocrinology
https://www.readbyqxmd.com/read/28317816/hemophagocytic-syndrome-secondary-to-tuberculosis-at-24-week-gestation
#2
Alexandra Arteaga Fernández, David Fernández de Velasco Pérez, M C Jiménez Fournier, J C Moreno Del Prado, B Paraíso Torras, M L Cañete Palomo
Hemophagocytic syndrome is a life-threatening disease characterized by the uncontrolled activation of macrophages, resulting in hemophagocytosis of blood cells in the bone marrow. A 20-year-old gravida at 23-week and 5-day gestation was admitted to hospital to evaluate fever up to 104°F of unknown origin, moderate cytopenia, and elevated levels of liver enzymes. Bone marrow biopsy confirmed hemophagocytic syndrome, and polymerase chain reaction came back positive for Mycobacterium tuberculosis. Supportive care and tuberculosis treatment resulted in clinical improvement...
January 2017: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28301468/recessive-coding-and-regulatory-mutations-in-fblim1-underlie-the-pathogenesis-of-chronic-recurrent-multifocal-osteomyelitis-crmo
#3
Allison J Cox, Benjamin W Darbro, Ronald M Laxer, Gabriel Velez, Xinyu Bing, Alexis L Finer, Albert Erives, Vinit B Mahajan, Alexander G Bassuk, Polly J Ferguson
Chronic recurrent multifocal osteomyelitis (CRMO) is a rare, pediatric, autoinflammatory disease characterized by bone pain due to sterile osteomyelitis, and is often accompanied by psoriasis or inflammatory bowel disease. There are two syndromic forms of CRMO, Majeed syndrome and DIRA, for which the genetic cause is known. However, for the majority of cases of CRMO, the genetic basis is unknown. Via whole-exome sequencing, we detected a homozygous mutation in the filamin-binding domain of FBLIM1 in an affected child with consanguineous parents...
2017: PloS One
https://www.readbyqxmd.com/read/28298335/hyperglycemia-and-hyperinsulinemia-induced-insulin-resistance-causes-alterations-in-cellular-bioenergetics-and-activation-of-inflammatory-signaling-in-lymphatic-muscle
#4
Yang Lee, James D Fluckey, Sanjukta Chakraborty, Mariappan Muthuchamy
Insulin resistance is a well-known risk factor for obesity, metabolic syndrome (MetSyn) and associated cardiovascular diseases, but its mechanisms are undefined in the lymphatics. Mesenteric lymphatic vessels from MetSyn or LPS-injected rats exhibited impaired intrinsic contractile activity and associated inflammatory changes. Hence, we hypothesized that insulin resistance in lymphatic muscle cells (LMCs) affects cell bioenergetics and signaling pathways that consequently alter contractility. LMCs were treated with different concentrations of insulin or glucose or both at various time points to determine insulin resistance...
March 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28291245/tyrosine-kinase-inhibitor-bibf1120-ameliorates-inflammation-angiogenesis-and-fibrosis-in-ccl4-induced-liver-fibrogenesis-mouse-model
#5
Büsra Öztürk Akcora, Gert Storm, Jai Prakash, Ruchi Bansal
Hepatic fibrosis, a progressive chronic disease mainly caused by hepatitis viral infections, alcohol abuse or metabolic syndrome leading to liver dysfunction and is the growing cause of mortality worldwide. Tyrosine kinase inhibitor BIBF1120 (Nintedanib) has been evaluated in clinical trials for idiopathic pulmonary fibrosis and advanced Hepatocellular carcinoma, but has not been explored for liver fibrosis yet. In this study, we aimed to investigate the therapeutic effects and mechanism of BIBF1120 in liver fibrogenesis...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28268026/in-hospital-mortality-in-febrile-lupus-patients-based-on-2016-eular-acr-printo-classification-criteria-for-macrophage-activation-syndrome
#6
Sung Soo Ahn, Byung-Woo Yoo, Seung Min Jung, Sang-Won Lee, Yong-Beom Park, Jason Jungsik Song
OBJECTIVE: To evaluate the clinical significance of the 2016 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR)/Pediatric Rheumatology International Trials Organization (PRINTO) classification criteria for macrophage activation syndrome (MAS) in patients with febrile systemic lupus erythematosus (SLE). METHODS: We performed a retrospective analysis of SLE patients with fever, who were admitted to Severance Hospital between December 2005 and May 2016...
February 8, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28265004/gain-of-function-mutation-of-tristetraprolin-impairs-negative-feedback-control-of-macrophages-in-vitro-yet-has-overwhelmingly-anti-inflammatory-consequences-in-vivo
#7
John D O'Neil, Ewan A Ross, Michael L Ridley, Qize Ding, Tina Tang, Dalya R Rosner, Thomas Crowley, Deepak Malhi, Jonathan L Dean, Tim Smallie, Christopher D Buckley, Andrew R Clark
The mRNA destabilizing factor tristetraprolin (TTP) binds in a sequence-specific manner to the 3' untranslated regions of many pro-inflammatory mRNAs and recruits complexes of nucleases to promote rapid mRNA turnover. Mice lacking TTP develop a severe, spontaneous inflammatory syndrome characterized by over-expression of tumor necrosis factor and other inflammatory mediators. However, TTP also employs the same mechanism to inhibit the expression of the potent anti-inflammatory cytokine interleukin 10. Perturbation of TTP function may therefore have mixed effects on inflammatory responses, either increasing or decreasing the expression of pro-inflammatory factors via direct or indirect mechanisms...
March 6, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28264871/immune-microenvironment-in-microsatellite-instable-endometrial-cancers-hereditary-or-sporadic-origin-matters
#8
Janelle B Pakish, Qian Zhang, Zhongyuan Chen, Han Liang, Gary Chisholm, Ying Yuan, Samuel C Mok, Russell J Broaddus, Karen Lu, Melinda S Yates
PURPOSE: Recent studies show that colorectal tumors with high microsatellite instability (MSI-H) have increased immunogenicity and response to immunotherapy compared to microsatellite stable (MSS) tumors. It is not yet clear if MSI-H endometrial cancer (EC) may also benefit from these therapies. It is also unknown whether immune response is equivalent in MSI-H EC with sporadic or inherited Lynch syndrome origins. EXPERIMENTAL DESIGN: Multiplexed fluorescent immunohistochemistry (IHC) was used to compare matched MSI-H (n=60) and MSS (n=96) EC specimens by evaluating immune cell populations in tumor and stroma compartments...
March 6, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28263744/gpr120-in-adipocytes-has-differential-roles-in-the-production-of-pro-inflammatory-adipocytokines
#9
Arif Ul Hasan, Koji Ohmori, Takeshi Hashimoto, Kazuyo Kamitori, Fuminori Yamaguchi, Takahisa Noma, Junsuke Igarashi, Kazuhito Tsuboi, Masaaki Tokuda, Akira Nishiyama, Masakazu Kohno
How nutritional excess leads to inflammatory responses in metabolic syndrome is not well characterized. Here, we evaluated the effects of ω-3 polyunsaturated fatty acid specific G-protein coupled receptor 120 (GPR120) activation on inflammatory pathways in adipocytes, and the influence of this process on macrophage migration. Using 3T3-L1 adipocytes, we found that agonizing GPR120 using its synthetic ligand, GSK137647, attenuated both basal and lipopolysaccharide-induced production of interleukin-6 (IL-6) and C-C motif chemokine ligand 2 (CCL2)...
March 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28259232/guillain-barr%C3%A3-syndrome
#10
REVIEW
Eelco F M Wijdicks, Christopher J Klein
Guillain-Barré syndrome is an acute inflammatory immune-mediated polyradiculoneuropathy presenting typically with tingling, progressive weakness, and pain. Variants and formes frustes may complicate recognition. The best known variant is the sensory ataxic form of Miller Fisher syndrome, which also affects the oculomotor nerves and the brain stem. Divergent pathologic mechanisms lead to demyelinating, axonal, or mixed demyelinating-axonal damage. In the demyelinating form, yet to be identified antigens are inferred by complement activation, myelin destruction, and macrophage-activated cleanup...
March 2017: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/28251009/idiopathic-pulmonary-hemosiderosis-in-a-child-with-recurrent-macrophage-activation-syndrome-secondary-to-systemic-juvenile-idiopathic-arthritis
#11
Kenan Barut, Sezgin Sahin, Amra Adrovic, Velat Sen, Ozgur Kasapcopur
Macrophage activation syndrome, a severe complication of systemic juvenile idiopathic arthritis and other inflammatory diseases, represents one of the most important rheumatological emergencies. Delayed diagnosis could lead to life-threatening complications. Pulmonary hemosiderosis has been classically characterized by a triad of anemia, hemoptysis, and lung infiltrates on chest radiogram. Although the majority of patients of pulmonary hemosiderosis are considered idiopathic, secondary hemosiderosis associated with known diseases could be seen...
2017: Case Reports in Pediatrics
https://www.readbyqxmd.com/read/28249676/murine-recombinant-angiotensin-converting-enzyme-2-attenuates-kidney-injury-in-experimental-alport-syndrome
#12
Eun Hui Bae, Fei Fang, Vanessa R Williams, Ana Konvalinka, Xiaohua Zhou, Vaibhav B Patel, Xuewen Song, Rohan John, Gavin Y Oudit, York Pei, James W Scholey
Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase in the renin-angiotensin system that catalyzes the breakdown of angiotensin II to angiotensin 1-7. We have reported that ACE2 expression in the kidney is reduced in experimental Alport syndrome but the impact of this finding on disease progression has not been studied. Accordingly, we evaluated effects of murine recombinant ACE2 treatment in Col4a3 knockout mice, a model of Alport syndrome characterized by proteinuria and progressive renal injury...
February 26, 2017: Kidney International
https://www.readbyqxmd.com/read/28249038/microvesicles-released-from-fat-laden-cells-promote-activation-of-hepatocellular-nlrp3-inflammasome-a-pro-inflammatory-link-between-lipotoxicity-and-non-alcoholic-steatohepatitis
#13
Stefania Cannito, Elisabetta Morello, Claudia Bocca, Beatrice Foglia, Elisa Benetti, Erica Novo, Fausto Chiazza, Mara Rogazzo, Roberto Fantozzi, Davide Povero, Salvatore Sutti, Elisabetta Bugianesi, Ariel E Feldstein, Emanuele Albano, Massimo Collino, Maurizio Parola
Non-Alcoholic Fatty Liver Disease (NAFLD) is a major form of chronic liver disease in the general population in relation to its high prevalence among overweight/obese individuals and patients with diabetes type II or metabolic syndrome. NAFLD can progress to steatohepatitis (NASH), fibrosis and cirrhosis and end-stage of liver disease but mechanisms involved are still incompletely characterized. Within the mechanisms proposed to mediate the progression of NAFLD, lipotoxicity is believed to play a major role...
2017: PloS One
https://www.readbyqxmd.com/read/28248832/pathophysiology-of-pediatric-multiple-organ-dysfunction-syndrome
#14
Joseph A Carcillo, Bradley Podd, Rajesh Aneja, Scott L Weiss, Mark W Hall, Timothy T Cornell, Thomas P Shanley, Lesley A Doughty, Trung C Nguyen
OBJECTIVE: To describe the pathophysiology associated with multiple organ dysfunction syndrome in children. DATA SOURCES: Literature review, research data, and expert opinion. STUDY SELECTION: Not applicable. DATA EXTRACTION: Moderated by an experienced expert from the field, pathophysiologic processes associated with multiple organ dysfunction syndrome in children were described, discussed, and debated with a focus on identifying knowledge gaps and research priorities...
March 2017: Pediatric Critical Care Medicine
https://www.readbyqxmd.com/read/28247848/relation-of-cytokine-profile-to-clinical-and-hemodynamic-features-in-young-patients-with-congenital-heart-disease-and-pulmonary-hypertension
#15
Leína Zorzanelli, Nair Maeda, Mariana Clavé, Ana Thomaz, Filomena Galas, Marlene Rabinovitch, Antonio Lopes
In congenital heart disease, severity of pulmonary hypertension and operability is defined by noninvasive parameters (clinical history, physical examination, and echocardiography) and sometimes, cardiac catheterization. We investigated how circulating levels of inflammatory mediators correlate with such parameters in a young pediatric population (age, 2.0 months to 3.1 years) and the effects of preoperative pulmonary vasodilator therapy with sildenafil. Cytokines were analyzed in serum using chemiluminescence signals...
January 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28245284/metabolically-distinct-weight-loss-by-10-12-cla-and-caloric-restriction-highlight-the-importance-of-subcutaneous-white-adipose-tissue-for-glucose-homeostasis-in-mice
#16
Laura J den Hartigh, Shari Wang, Leela Goodspeed, Tomasz Wietecha, Barbara Houston, Mohamed Omer, Kayoko Ogimoto, Savitha Subramanian, G A Nagana Gowda, Kevin D O'Brien, Karl J Kaiyala, Gregory J Morton, Alan Chait
BACKGROUND: Widely used as a weight loss supplement, trans-10,cis-12 conjugated linoleic acid (10,12 CLA) promotes fat loss in obese mice and humans, but has also been associated with insulin resistance. OBJECTIVE: We therefore sought to directly compare weight loss by 10,12 CLA versus caloric restriction (CR, 15-25%), an acceptable healthy method of weight loss, to determine how 10,12 CLA-mediated weight loss fails to improve glucose metabolism. METHODS: Obese mice with characteristics of human metabolic syndrome were either supplemented with 10,12 CLA or subjected to CR to promote weight loss...
2017: PloS One
https://www.readbyqxmd.com/read/28241868/dynamic-changes-in-bronchoalveolar-macrophages-and-cytokines-during-infection-of-pigs-with-a-highly-or-low-pathogenic-genotype-1-prrsv-strain
#17
Patricia Renson, Nicolas Rose, Mireille Le Dimna, Sophie Mahé, André Keranflec'h, Frédéric Paboeuf, Catherine Belloc, Marie-Frédérique Le Potier, Olivier Bourry
Porcine reproductive and respiratory syndrome virus (PRRSV) replicates primarily in pulmonary alveolar macrophages (PAMs) and the resulting lung damage is influenced by strain virulence. To better understand the pathogenesis of PRRSV infection, we performed a longitudinal study of the PAM population and lung cytokines in specific pathogen-free pigs infected either with the highly pathogenic Lena strain or with the low pathogenic Finistere strain in comparison to uninfected pigs. Bronchoalveolar lavage fluid (BALF) and blood were collected to follow viral, cellular and cytokine changes in lung with respect to clinical signs and systemic events...
February 27, 2017: Veterinary Research
https://www.readbyqxmd.com/read/28240747/antibodies-against-nonstructural-protein-1-protect-mice-from-dengue-virus-induced-mast-cell-activation
#18
Ya-Ting Chu, Shu-Wen Wan, Yu-Chang Chang, Chien-Kuo Lee, Betty A Wu-Hsieh, Robert Anderson, Yee-Shin Lin
Dengue virus (DENV) infection causes dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). DHF/DSS patients have been reported to have increased levels of urinary histamine, chymase, and tryptase, which are major granule-associated mediators from mast cells. Previous studies also showed that DENV-infected human mast cells induce production of proinflammatory cytokines and chemokines, suggesting a role played by mast cells in vascular perturbation as well as leukocyte recruitment. In this study, we show that DENV but not UV-inactivated DENV enhanced degranulation of mast cells and production of chemokines (MCP-1, RANTES, and IP-10) in a mouse model...
February 27, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28236433/regulators-of-mitochondrial-quality-control-differ-in-subcutaneous-fat-of-metabolically-healthy-and-unhealthy-obese-monkeys
#19
Kylie Kavanagh, Ashley T Davis, Diane E Peters, Andre C LeGrand, Manish S Bharadwaj, Anthony J A Molina
OBJECTIVE: Obesity exists with and without accompanying cardiometabolic disease, termed metabolically unhealthy obesity (MUO) and healthy obesity (MHO), respectively. Underlying differences in the ability of subcutaneous (SQ) fat to respond to nutrient excess are emerging as a key pathway. This study aimed to document the first spontaneous animal model of MHO and MUO and differences in SQ adipose tissue. METHODS: Vervet monkeys (Chlorocebus aethiops; N = 171) were screened for metabolic syndrome...
February 25, 2017: Obesity
https://www.readbyqxmd.com/read/28236156/antimalarial-myopathy-in-a-systemic-lupus-erythematosus-patient-with-quadriparesis-and-seizures-a-case-based-review
#20
REVIEW
Kashif Jafri, Hengameh Zahed, Katherine D Wysham, Sarah Patterson, Amber L Nolan, Matthew D Bucknor, R Krishna Chaganti
Weakness, seizures, and encephalopathy have a broad differential diagnosis in patients with systemic lupus erythematosus (SLE). We present a case of a 26-year-old female with a recent diagnosis of SLE who experienced a clinical deterioration with quadriparesis, seizures, and encephalopathy. Her quadriparesis was found to be secondary to biopsy-proven hydroxychloroquine-induced myopathy with concomitant inflammatory myopathy. Her seizures and encephalopathy were suspected to be multifactorial in the setting of sepsis and critical illness with possible contributions from neuropsychiatric manifestations of SLE and macrophage activation syndrome...
February 24, 2017: Clinical Rheumatology
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