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Death clearance

Fariborz Mobarrez, Anna Vikerfors, Johanna T Gustafsson, Iva Gunnarsson, Agneta Zickert, Anders Larsson, David S Pisetsky, Håkan Wallén, Elisabet Svenungsson
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by circulating autoantibodies and the formation of immune complexes. In these responses, the selecting self-antigens likely derive from the remains of dead and dying cells, as well as from disturbances in clearance. During cell death/activation, microparticles (MPs) can be released to the circulation. Previous MP studies in SLE have been limited in size and differ regarding numbers and phenotypes. Therefore, to characterize MPs more completely, we investigated 280 SLE patients and 280 individually matched controls...
October 25, 2016: Scientific Reports
J N Sheets, M Iwanicki, J F Liu, B E Howitt, M S Hirsch, J A A Gubbels, R Drapkin, K A Egland
The cause of death among the majority of epithelial ovarian cancer (EOC) patients involves passive dissemination of cancer cells within the peritoneal cavity and subsequent implantation of cancer spheroids into adjacent organs. Thus, it is important to identify the factors that mediate EOC metastasis and implantation, including clearance of the mesothelium. Sushi domain containing 2 (SUSD2) encodes a type I transmembrane protein containing several functional domains inherent to adhesion molecules. Immunohistochemical analysis determined the presence of SUSD2 in several subtypes of EOC, with the strongest staining observed in high-grade serous ovarian carcinomas (HGSOCs)...
October 24, 2016: Oncogenesis
Xuehua Piao, Soh Yamazaki, Sachiko Komazawa-Sakon, Sanae Miyake, Osamu Nakabayashi, Takeyuki Kurosawa, Tetsuo Mikami, Minoru Tanaka, Nico Van Rooijen, Masaki Ohmuraya, Akira Oikawa, Yuko Kojima, Soichiro Kakuta, Yasuo Uchiyama, Masato Tanaka, Hiroyasu Nakano
: Tissue-resident macrophages and bone marrow (BM)-derived monocytes play a crucial role in the maintenance of tissue homeostasis; however, their contribution to recovery from acute tissue injury is not fully understood. To address this issue, we generated an acute murine liver injury model using hepatocyte-specific Cflar-deficient (Cflar(Hep-low) ) mice. Cellular FLICE-inhibitory protein (cFLIP) expression was downregulated in Cflar-deficient hepatocytes, which thereby increased susceptibility of hepatocytes to death receptor-induced apoptosis...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Zsolt Sziklavari, Michael Ried, Florian Zeman, Christian Grosser, Tamas Szöke, Reiner Neu, Rudolf Schemm, Hans-Stefan Hofmann
BACKGROUND: This retrospective study analyzed the effectiveness of intrathoracic negative pressure therapy for debilitated patients with empyema and compared the short-term and long-term outcomes of three different intrapleural vacuum-assisted closure (VAC) techniques. METHODS: We investigated 43 consecutive (pre)septic patients with poor general condition (Karnofsky index ≤ 50 %) and multimorbidity (≥ 3 organ diseases) or immunosuppression, who had been treated for primary, postoperative, or recurrent pleural empyema with VAC in combination with open window thoracostomy (OWT-VAC) with minimally invasive technique (Mini-VAC), and instillation (Mini-VAC-Instill)...
October 21, 2016: Journal of Cardiothoracic Surgery
Roxann Diez Gross, Ronit Gisser, Gregory Cherpes, Katie Hartman, Rishi Maheshwary
Prader-Willi Syndrome (PWS) is caused by a genetic imprinting abnormality resulting from the lack of expression of the paternal genes at 15q11-q13. Intellectual disability, low muscle tone, and life-threatening hyperphagia are hallmarks of the phenotype. The need for the Heimlich maneuver, death from choking, and pulmonary infection occur in a disproportionally high number of persons with PWS. The widely held belief is that eating behaviors are responsible for choking and aspiration; yet, no investigation had sought to determine if swallowing impairments were present in persons with PWS...
October 19, 2016: American Journal of Medical Genetics. Part A
Aditya K Sharma, Divya Arora, Lalit K Singh, Aakriti Gangwal, Andaleeb Sajid, Virginie Molle, Yogendra Singh, Vinay K Nandicoori
Protein phosphatases play vital roles in phosphorylation-mediated cellular signaling. While there are 11 serine/threonine protein kinases in Mycobacterium tuberculosis, only one serine/threonine phosphatase, PstP, has been identified. Although PstP has been biochemically characterized and multiple in vitro substrates identified, its physiological role has not yet been elucidated. In this study we have investigated the impact of PstP on cell growth and survival of the pathogen in the host. Overexpression of PstP led to elongated cells and partially compromised survival...
October 7, 2016: Journal of Biological Chemistry
Zhanna Kobalava
The burden of cardiovascular diseases (CVD) in general and heart failure (HF) in particular continues to increase worldwide. CVD are major contributors to death and morbidity and recognized as important drivers of healthcare expenditure. Chronic overactivity of the renin-angiotensin-aldosterone system (RAAS) plays a key role in human hypertension and HF pathophysiology. RAAS is fundamental in the overall regulation of cardiovascular homeostasis through the actions of hormones, which regulate vascular tone, and specifically blood pressure through vasoconstriction and renal sodium and water retention...
September 2016: Journal of Hypertension
Chrisovalantis Papadopoulos, Philipp Kirchner, Monika Bug, Daniel Grum, Lisa Koerver, Nina Schulze, Robert Poehler, Alina Dressler, Sven Fengler, Khalid Arhzaouy, Vanda Lux, Michael Ehrmann, Conrad C Weihl, Hemmo Meyer
Rupture of endosomes and lysosomes is a major cellular stress condition leading to cell death and degeneration. Here, we identified an essential role for the ubiquitin-directed AAA-ATPase, p97, in the clearance of damaged lysosomes by autophagy. Upon damage, p97 translocates to lysosomes and there cooperates with a distinct set of cofactors including UBXD1, PLAA, and the deubiquitinating enzyme YOD1, which we term ELDR components for Endo-Lysosomal Damage Response. Together, they act downstream of K63-linked ubiquitination and p62 recruitment, and selectively remove K48-linked ubiquitin conjugates from a subpopulation of damaged lysosomes to promote autophagosome formation...
October 17, 2016: EMBO Journal
Hajera Amatullah, Yuexin Shan, Brittany L Beauchamp, Patricia L Gali, Sahil Gupta, Tatiana Maron-Gutierrez, Edwin R Speck, Alison E Fox-Robichaud, Jennifer L Y Tsang, Shirley H J Mei, Tak W Mak, Patricia Rm Rocco, John W Semple, Haibo Zhang, Pingzhao Hu, John C Marshall, Duncan J Stewart, Mary-Ellen Harper, Patricia C Liaw, W Conrad Liles, Claudia C Dos Santos
RATIONALE & OBJECTIVES: Effective and rapid bacterial clearance is a fundamental determinant of outcome(s) in sepsis. DJ-1 is a well-established reactive oxygen species (ROS) scavenger. As cellular ROS status is pivotal to inflammation and bacterial killing, we determined the role of DJ-1 in bacterial sepsis. METHODS: We used cell and murine models with gain and loss of function experiments, plasma and cells from septic patients. MEASUREMENTS & RESULTS: Stimulation of bone marrow derived macrophages (BMM) with endotoxin resulted in increased DJ-1 mRNA and protein expression...
October 13, 2016: American Journal of Respiratory and Critical Care Medicine
I-Chih Chen, Chao-Chin Yu, Yi-Hsuan Wu, Ting-Hsing Chao
BACKGROUND: Inflammation plays an important role in the pathogenesis of cardiovascular disease in patients with advanced chronic kidney disease (CKD). Neutrophil-to-lymphocyte ratio (NLR), an inflammatory biomarker, has not been evaluated in patients who have advanced CKD with peripheral artery disease (PAD) undergoing percutaneous transluminal angioplasty (PTA), especially in Taiwan. METHODS: We retrospectively evaluated 148 advanced CKD (creatinine clearance rate ≤ 30 mL/min/1...
September 2016: Acta Cardiol Sin
Lisa Brennan, Josef Khoury, Marc Kantorow
Age-related cataract is associated with oxidative stress and death of lens epithelial cells (LECs) whose survival is dependent on functional mitochondrial populations. Oxidative stress-induced depolarization/damage of LEC mitochondria results in increased reactive oxygen species (ROS) levels and cell death suggesting the need for a LEC mechanism to remove mitochondria depolarized/damaged upon oxidative stress exposure to prevent ROS release and LEC death. To date, a mechanism(s) for removal of depolarized/damaged LEC mitochondria has yet to be identified and the importance of eliminating oxidative stress-damaged mitochondria to prevent LEC ROS release and death has not been established...
October 1, 2016: Biochimica et Biophysica Acta
Seung-Kee Min, Young Hwan Kim, Jin Hyun Joh, Jin Mo Kang, Ui Jun Park, Hyung-Kee Kim, Jeong-Hwan Chang, Sang Jun Park, Jang Yong Kim, Jae Ik Bae, Sun Young Choi, Chang Won Kim, Sung Il Park, Nam Yeol Yim, Yong Sun Jeon, Hyun-Ki Yoon, Ki Hyuk Park
Lower extremity deep vein thrombosis is a serious medical condition that can result in death or major disability due to pulmonary embolism or post-thrombotic syndrome. Appropriate diagnosis and treatment are required to improve symptoms and salvage the affected limb. Early thrombus clearance rapidly resolves symptoms related to venous obstruction, restores valve function and reduces the incidence of post-thrombotic syndrome. Recently, endovascular treatment has been established as a standard method for early thrombus removal...
September 2016: Vascular Specialist International
Erika N Guerrero, Haibo Wang, Joy Mitra, Pavana M Hegde, Sara E Stowell, Nicole F Liachko, Brian C Kraemer, Ralph M Garruto, K S Rao, Muralidhar L Hegde
Amyotrophic lateral sclerosis (ALS), a common motor neuron disease affecting two per 100,000 people worldwide, encompasses at least five distinct pathological subtypes, including, ALS-SOD1, ALS-C9orf72, ALS-TDP-43, ALS-FUS and Guam-ALS. The etiology of a major subset of ALS involves toxicity of the TAR DNA-binding protein-43 (TDP-43). A second RNA/DNA binding protein, fused in sarcoma/translocated in liposarcoma (FUS/TLS) has been subsequently associated with about 1% of ALS patients. While mutations in TDP-43 and FUS have been linked to ALS, the key contributing molecular mechanism(s) leading to cell death are still unclear...
September 28, 2016: Progress in Neurobiology
Meghan T Walsh, M Mahmood Hussain
Homozygous familial hypercholesterolemia (HoFH) is a polygenic disease arising from defects in the clearance of plasma low-density lipoprotein (LDL), which results in extremely elevated plasma LDL cholesterol (LDL-C) and increased risk of atherosclerosis, coronary heart disease, and premature death. Conventional lipid-lowering therapies, such as statins and ezetimibe, are ineffective at lowering plasma cholesterol to safe levels in these patients. Other therapeutic options, such as LDL apheresis and liver transplantation, are inconvenient, costly, and not readily available...
October 1, 2016: Critical Reviews in Clinical Laboratory Sciences
Uriel Trahtemberg, Amir Grau, Adi Tabib, Mizhir Atallah, Alon Krispin, Dror Mevorach
Human monocyte-derived dendritic cells (mdDCs) are versatile cells that are used widely for research and experimental therapies. Although different culture conditions can affect their characteristics, there are no known subpopulations. Since monocytes differentiate into dendritic cells (DCs) in a variety of tissues and contexts, we asked whether they can give rise to different subpopulations. In this work we set out to characterize two human mdDC subpopulations that we identified and termed small (DC-S) and large (DC-L)...
2016: PloS One
Ine Jorgensen, Joseph P Lopez, Stefan A Laufer, Edward A Miao
Inflammasomes activate caspase-1, initiating a lytic form of programmed cell death termed pyroptosis, which is an important innate immune defense mechanism against intracellular infections. We recently demonstrated in a mouse infection model of pyroptosis that instead of releasing bacteria into the extracellular space, bacteria remain trapped within the pyroptotic cell corpse, termed the pore-induced intracellular trap (PIT). This trapping mediates efferocytosis of the PIT and associated bacteria by neutrophils; bacteria are subsequently killed via neutrophil ROS...
September 28, 2016: European Journal of Immunology
Suzanne M Boyle, Yimei Li, F P Wilson, Joel D Glickman, Harold I Feldman
♦ Background: Total body water (V) is an imprecise metric for normalization of dialytic urea clearance (Kt). This poses a risk of early mortality/technique failure (TF). We examined differences in the distribution of peritoneal Kt/V when V was calculated with actual weight (AW), ideal weight (IW), and adjusted weight (ADW). We also examined the associations of these Kt/V measurements, Kt/body surface area (BSA), and non-normalized Kt with mortality and TF. ♦ Methods: This is a retrospective cohort study of 534 incident peritoneal dialysis (PD) patients from the Dialysis Morbidity and Mortality Study Wave 2 linked with United States Renal Data System through 2010...
September 28, 2016: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
Daniel W Summers, Daniel A Gibson, Aaron DiAntonio, Jeffrey Milbrandt
Axon injury in response to trauma or disease stimulates a self-destruction program that promotes the localized clearance of damaged axon segments. Sterile alpha and Toll/interleukin receptor (TIR) motif-containing protein 1 (SARM1) is an evolutionarily conserved executioner of this degeneration cascade, also known as Wallerian degeneration; however, the mechanism of SARM1-dependent neuronal destruction is still obscure. SARM1 possesses a TIR domain that is necessary for SARM1 activity. In other proteins, dimerized TIR domains serve as scaffolds for innate immune signaling...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Mina M G Youssef, Diane Cameron, Philip H Pucher, Sisse Olsen, Douglas Ferguson
BACKGROUND: Management of micrometastasis in the sentinel node is a controversial topic. Most of the guidelines don't recommend further axillary treatment if micrometastasis are the only finding in the sentinel node. However, some evidence suggests that micrometastasis have significant effect on long term outcomes and therefore indicate systemic treatment. METHOD: Retrospective cohort study reviewing the management of patients with micrometastasis in the sentinel nodes...
September 23, 2016: Breast: Official Journal of the European Society of Mastology
J X Zhang, M Yin, X M Chen, C Li, D W Wu, S F Ding, B F Du, H P Guo, W D Qin, H N Yang, H Wang
Objective: To investigate the predictive value of early lactate area for mortality in elderly patients with septic shock. Methods: From January 2012 to December 2013, a prospective study was conducted in the Department of Critical Care Medicine, Qilu Hospital of Shandong University. A total of 115 septic shock patients with age ≥65 years were included in the study. Serum lactate was measured every 6 hours, the lactate indicators, including early lactate area, APACHE Ⅱ score etc were recorded. Results: The overall 28-day mortality rate was 67...
September 6, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
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