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Citrullination

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https://www.readbyqxmd.com/read/29341591/the-development-of-benzimidazole-based-clickable-probes-for-the-efficient-labeling-of-cellular-protein-arginine-deiminases-pads
#1
Venkatesh J Nemmara, Venkataraman Subramanian, Aaron Muth, Santanu Mondal, Ari J Salinger, Aaron J Maurais, Ronak Tilvawala, Eranthie Weerapana, Paul R Thompson
Citrullination is the post-translational hydrolysis of peptidyl-arginines to form peptidyl-citrulline, a reaction that is catalyzed by the protein arginine deiminases (PADs), a family of calcium-regulated enzymes. Aberrantly increased protein citrullination is associated with a slew of autoimmune diseases (e.g., rheumatoid arthritis (RA), multiple sclerosis, lupus, and ulcerative colitis) and certain cancers. Given the clear link between increased PAD activity and human disease, the PADs are therapeutically relevant targets...
January 17, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29341486/rheumatoid-arthritis-and-periodontal-disease-what-are-the-similarities-and-differences
#2
REVIEW
Rongbin Li, Cheng Tian, Arnold Postlethwaite, Yan Jiao, Franklin Garcia-Godoy, Debendra Pattanaik, Dongmei Wei, Weikuan Gu, Jianwei Li
Rheumatoid arthritis (RA) and periodontal disease (PD) are chronic inflammatory diseases that share similar osteoclasia, human leukocyte antigen-DR4 allelic genes and immunological profile, and characteristic cytokines. Smoking can contribute to more severe RA and PD; secretion of pro-inflammatory mediators destroys the soft synovial membrane and periodontium, respectively. Anti-citrullinated protein antibodies and anti-α-enolase antibody are characteristic of these two diseases. Some studies suggest that PD may be associated with RA...
December 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/29338885/concurrence-of-rheumatoid-arthritis-and-calcium-pyrophosphate-deposition-disease-a-case-collection-and-review-of-the-literature
#3
Viktoriya Sabchyshyn, Irina Konon, Lawrence M Ryan, Ann K Rosenthal
OBJECTIVE: Calcium pyrophosphate deposition disease (CPDD) is arthritis caused by calcium pyrophosphate (CPP) crystal deposition in joints. It is commonly associated with aging as well as a handful of metabolic syndromes. Recent epidemiologic studies suggest a positive association of CPDD and rheumatoid arthritis (RA). Yet how these diseases are related remains unclear. We set out to describe 21 well-characterized patients with both diagnoses. METHODS: Medical records of patients with both RA and CPDD identified at a single academic practice site were reviewed for age, gender, age of CPDD and RA onset, disease duration, joint involvement, and lab values including rheumatoid factor (RF), cyclic citrullinated peptide antibody (CCP), iron studies, and parathyroid hormone and calcium levels...
December 2, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/29337988/l-arginine-supplementation-reduces-mortality-and-improves-disease-outcome-in-mice-infected-with-trypanosoma-cruzi
#4
Sofía Carbajosa, Héctor O Rodríguez-Angulo, Susana Gea, Carlos Chillón-Marinas, Cristina Poveda, María C Maza, Diana Colombet, Manuel Fresno, Núria Gironès
Chagas disease caused by Trypanosoma cruzi is a neglected disease that affects about 7 million people in Latin America, recently emerging on other continents due to migration. As infection in mice is characterized by depletion of plasma L-arginine, the effect on infection outcome was tested in mice with or without L-arginine supplementation and treatment with 1400W, a specific inhibitor of inducible nitric oxide synthase (iNOS). We found that levels of L-arginine and citrulline were reduced in the heart and plasma of infected mice, whereas levels of asymmetric dimethylarginine, an endogenous iNOS inhibitor, were higher...
January 16, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29337196/nicorandil-and-theophylline-can-protect-experimental-rats-against-complete-freund-s-adjuvant-induced-rheumatoid-arthritis-through-modulation-of-jak-stat-rankl-signaling-pathway
#5
Ahmed Gaafar Ahmed Gaafar, Basim Anwar Shehata Messiha, Ahmed Mohamed Labib Abdelkafy
Signaling pathways are interesting fields of study of pathogenesis and treatment trials. We elucidated the possible protective effects of nicorandil (15mg/kg/day) and theophylline (20mg/kg/day) on experimentally-induced RA, focusing on the role of JAK (Janus Kinase) / STAT (Signal Transducer and Activator of Transcription) / RANKL (Receptor Activator of Nuclear factor-Kappa B Ligand) / cytokine signaling pathway. Four sets of experiments were performed. First, effect of test agents on normal animals was evaluated...
January 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29336646/anti-cyclic-citrullinated-peptide-antibodies-other-common-autoantibodies-and-smoking-as-risk-factors-for-lymphoma-in-patients-with-rheumatoid-arthritis
#6
E Baecklund, C Backlin, J Rönnelid, R Toes, Twj Huizinga, E Åhlin, J Askling, F H Hochberg, L Klareskog, J Kay, K E Smedby
OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of lymphoma. There is no biomarker to indicate future lymphoma risk in RA and it is not known whether factors associated with an increased risk of RA also confer an increased risk of lymphoma. We investigated whether anti-cyclic citrullinated peptide (CCP) antibodies, other autoantibodies, and smoking, are associated with lymphoma development in RA. METHOD: From two population-based case-control studies, the Scandinavian Lymphoma Etiology (SCALE) study and the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) I study, we identified lymphoma cases with a validated RA diagnosis (n = 50), to whom we matched study participants with RA but no lymphoma (n = 261), lymphoma but no RA (n = 257), and neither RA nor lymphoma (n = 233)...
January 16, 2018: Scandinavian Journal of Rheumatology
https://www.readbyqxmd.com/read/29336618/rheumatoid-arthritis-a-single-center-egyptian-experience
#7
B R Sakr, M M Elfishawi, M H ElArousy, A K Hatw, A N AbdulKarim, A B Tammam, A N Kotp, M E Hamed, I E Genedy, E D El Desouky, Z O Nawito
OBJECTIVE: Demonstration of rheumatoid arthritis (RA) characteristics in a large cohort of Egyptian patients. METHODS: Retrospective analysis of data of 3219 RA patients attending the Rheumatology outpatient clinic, Kasr Alainy Hospital, Cairo University; from January 1995 till December 2015. RESULTS: Mean age at disease onset was 36.1 ±13.4 years; 2774 (84%) were females and mean disease duration was 12.9 ±7.9 years. Regarding number of joint affected at disease onset; polyarticular pattern was found in 77...
January 16, 2018: Immunological Investigations
https://www.readbyqxmd.com/read/29336365/il1f7-gene-polymorphism-is-not-associated-with-rheumatoid-arthritis-susceptibility-in-the-northern-chinese-han-population-a-case-control-study
#8
Xiao-Ying Zhang, Yu Zuo, Chun Li, Xin Tu, Hu-Ji Xu, Jian-Ping Guo, Zhan-Guo Li, Rong Mu
BACKGROUND: Interleukin (IL)-37, also called IL1F7, is a natural inhibitor of inflammatory and immune responses. It is involved in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the role of IL1F7 gene polymorphism in RA susceptibility in a large cohort of patients. METHODS: Five selected single-nucleotide polymorphisms in IL1F7 genes (rs2723186, rs3811046, rs4241122, rs4364030, and rs4392270) were genotyped by TaqMan Allelic Discrimination in Northern Chinese Han population...
January 20, 2018: Chinese Medical Journal
https://www.readbyqxmd.com/read/29335340/anticitrullinated-protein-antibodies-induce-inflammatory-gene-expression-profile-in-peripheral-blood-cells-from-ccp-positive-patients-with-ra
#9
Smadar Gertel, Gidi Karmon, Eszter Szarka, Ora Shovman, Esther Houri-Levi, Edna Mozes, Yehuda Shoenfeld, Howard Amital
OBJECTIVE: Anticitrullinated protein antibodies (ACPA) have major diagnostic significance in rheumatoid arthritis (RA). ACPA are directed against different citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen. The presence of ACPA is associated with joint damage and extraarticular manifestations, suggesting that ACPA may have a significant role in the pathogenesis of RA. METHODS: To verify the effect of ACPA on RA-immune cells, peripheral blood mononuclear cells (PBMC) from cyclic citrullinated peptide (CCP)-positive patients with RA and healthy controls were cocultured in vitro with ACPA...
January 15, 2018: Journal of Rheumatology
https://www.readbyqxmd.com/read/29330439/induction-of-protein-citrullination-and-auto-antibodies-production-in-murine-exposed-to-nickel-nanomaterials
#10
Bashir M Mohamed, Noreen T Boyle, Anja Schinwald, Bruno Murer, Ronan Ward, Omar K Mahfoud, Tatsiana Rakovich, Kieran Crosbie-Staunton, Steven G Gray, Ken Donaldson, Yuri Volkov, Adriele Prina-Mello
Citrullination, or the post-translational deimination of polypeptide-bound arginine, is involved in several pathological processes in the body, including autoimmunity and tumorigenesis. Recent studies have shown that nanomaterials can trigger protein citrullination, which might constitute a common pathogenic link to disease development. Here we demonstrated auto-antibody production in serum of nanomaterials-treated mice. Citrullination-associated phenomena and PAD levels were found to be elevated in nanomaterials -treated cell lines as well as in the spleen, kidneys and lymph nodes of mice, suggesting a systemic response to nanomaterials injection, and validated in human pleural and pericardial malignant mesothelioma (MM) samples...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330273/rheumatoid-disease-an-unusual-cause-of-relapsing-meningoencephalitis
#11
Sian K Alexander, Maria Di Cicco, Ute Pohl, Alberto Cifelli
A 73-year-old man presented with three episodes of dysphasia and disinhibited behaviour, a single seizure and transient ischaemic attack-like events characterised by right arm and/or leg weakness. These episodes were separated by month-long asymptomatic intervals. Medical history included rheumatoid arthritis, which was clinically quiescent on leflunomide.Repeated cerebrospinal fluid examination showed a persistent lymphocytosis with mildly reduced glucose and elevated protein; oligoclonal bands and viral PCR were negative...
January 12, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29325226/citrullinated-histone-h3-a-biomarker-of-neutrophil-extracellular-trap-formation-predicts-the-risk-of-venous-thromboembolism-in-cancer-patients
#12
Lisa-Marie Mauracher, Florian Posch, Kimberly Martinod, Ella Grilz, Thomas Däullary, Lena Hell, Christine Brostjan, Christoph Zielinski, Cihan Ay, Denisa D Wagner, Ingrid Pabinger, Johannes Thaler
BACKGROUND: Neutrophil extracellular traps (NETs) are decondensed chromatin fibers which might play a role in the prothrombotic state of cancer patients. OBJECTIVES: Here we investigated whether citrullinated histone H3 (H3Cit), a biomarker for NET formation, cell-free DNA (cfDNA), and nucleosomes predict venous thromboembolism (VTE) in cancer patients. PATIENTS/METHODS: Nine-hundred-forty-six patients with newly-diagnosed cancer or progression after remission were enrolled in this prospective observational cohort study...
January 11, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29324871/citrullinated-histone-h3-as-a-novel-prognostic-blood-marker-in-patients-with-advanced-cancer
#13
Charlotte Thålin, Staffan Lundström, Cedric Seignez, Maud Daleskog, Annika Lundström, Peter Henriksson, Thomas Helleday, Mia Phillipson, Håkan Wallén, Mélanie Demers
Citrullinated histone H3 (H3Cit) is a central player in the neutrophil release of nuclear chromatin, known as neutrophil extracellular traps (NETs). NETs have been shown to elicit harmful effects on the host, and were recently proposed to promote tumor progression and spread. Here we report significant elevations of plasma H3Cit in patients with advanced cancer compared with age-matched healthy individuals. These elevations were specific to cancer patients as no increase was observed in severely ill and hospitalized patients with a higher non-malignant comorbidity...
2018: PloS One
https://www.readbyqxmd.com/read/29317506/the-interplay-between-citrullination-and-hla-drb1-polymorphism-in-shaping-peptide-binding-hierarchies-in-rheumatoid-arthritis
#14
Yi Tian Ting, Jan Petersen, Sri H Ramarathinam, Stephen W Scally, Khai L Loh, Ranjeny Thomas, Anish Suri, Daniel G Baker, Anthony W Purcell, Hugh H Reid, Jamie Rossjohn
The HLA-DRB1 locus is strongly associated with rheumatoid arthritis (RA) susceptibility, whereupon citrullinated self-peptides bind to HLA-DR molecules bearing the shared epitope (SE) amino acid motif.  However, the differing propensity for citrullinated/non-citrullinated self-peptides to bind given HLA-DR allomorphs remains unclear.  Here, we used a fluorescence polarisation assay to determine a hierarchy of binding affinities of 34 self-peptides implicated in RA against three HLA-DRB1 allomorphs (HLA-DRB1*04:01/*04:04/*04:05) each possessing the SE motif...
January 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29314830/x-ray-structures-of-the-proprotein-convertase-furin-bound-with-substrate-analog-inhibitors-reveal-substrate-specificity-determinants-beyond-the-s4-pocket
#15
Sven O Dahms, Kornelia Hardes, Torsten Steinmetzer, Manuel E Than
The proprotein convertase (PC) furin is a highly specific serine protease modifying and thereby activating proteins in the secretory pathway by proteolytic cleavage. Its substrates are involved in many diseases including cancer and infections caused by bacteria and viruses. Understanding furin's substrate specificity is of crucial importance for the development of pharmacologically applicable inhibitors. Using protein X-ray crystallography we investigated the extended substrate binding site of furin in complex with three peptide derived inhibitors at up to 1...
January 9, 2018: Biochemistry
https://www.readbyqxmd.com/read/29314318/two-novel-cps1-mutations-in-a-case-of-carbamoyl-phosphate-synthetase-1-deficiency-causing-hyperammonemia-and-leukodystrophy
#16
Xihui Chen, Lijuan Yuan, Mao Sun, Qingbo Liu, Yuanming Wu
BACKGROUND: Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is a rare autosomal recessive disorder of the urea cycle, mostly characterized by hyperammonemia and the concomitant leukodystrophy. The onset of CPS1D can be at any age, and the clinical manifestations are variable and atypical. Genetic tests are indispensable for accurate diagnosis of CPS1D on the basis of biochemical tests. METHODS: Blood tandem mass spectrometric analysis and urea organic acidemia screening were performed on a Chinese neonatal patient with low activity, recurrent seizures, and hyperammonemia...
January 4, 2018: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/29310063/global-arginine-bioavailability-ratio-is-decreased-in-patients-with-major-depressive-disorder
#17
Toni Ali-Sisto, Tommi Tolmunen, Heimo Viinamäki, Pekka Mäntyselkä, Minna Valkonen-Korhonen, Heli Koivumaa-Honkanen, Kirsi Honkalampi, Anu Ruusunen, Jatin Nandania, Vidya Velagapudi, Soili M Lehto
BACKGROUND: Major depressive disorder (MDD) is characterized by increased oxidative and nitrosative stress. We compared nitric oxide metabolism, i.e., the global arginine bioavailability ratio (GABR) and related serum amino acids, between MDD patients and non-depressed controls, and between remitted and non-remitted MDD patients. METHODS: Ninety-nine MDD patients and 253 non-depressed controls, aged 20-71 years, provided background data via questionnaires. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry to determine the serum levels of ornithine, arginine, citrulline, and symmetric and asymmetric dimethylarginine...
December 27, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29309057/macrophage-extracellular-trap-formation-promoted-by-platelet-activation-is-a-key-mediator-of-rhabdomyolysis-induced-acute-kidney-injury
#18
Koshu Okubo, Miho Kurosawa, Mako Kamiya, Yasuteru Urano, Akari Suzuki, Kazuhiko Yamamoto, Koji Hase, Koichiro Homma, Junichi Sasaki, Hiroaki Miyauchi, Tatsuo Hoshino, Matsuhiko Hayashi, Tanya N Mayadas, Junichi Hirahashi
Rhabdomyolysis is a serious syndrome caused by skeletal muscle injury and the subsequent release of breakdown products from damaged muscle cells into systemic circulation. The muscle damage most often results from strenuous exercise, muscle hypoxia, medications, or drug abuse and can lead to life-threatening complications, such as acute kidney injury (AKI). Rhabdomyolysis and the AKI complication can also occur during crush syndrome, an emergency condition that commonly occurs in victims of natural disasters, such as earthquakes, and man-made disasters, such as wars and terrorism...
January 8, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29308319/citrullinated-%C3%AE-enolase-is-an-effective-target-for-anti-cancer-immunity
#19
Katherine Cook, Ian Daniels, Peter Symonds, Tracy Pitt, Mohamed Gijon, Wei Xue, Rachael Metheringham, Lindy Durrant, Victoria Brentville
Targeting post-translationally modified epitopes may provide a new strategy for generating tumor specific immune responses. Citrullination is the post-translational modification of arginine to citrulline catalyzed by peptidylarginine deaminase (PAD) enzymes. Presentation of citrullinated peptides on MHC-II has been associated with autophagy. Tumors upregulate autophagy and present citrullinated peptides in response to stresses including nutrient deprivation, oxygen deprivation, redox stress and DNA damage, making them good targets for immune attack...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29308281/case-series-monoarticular-rheumatoid-arthritis
#20
Jeffrey Sarazin, Elena Schiopu, Rajaie Namas
Objective: Monoarticular presentation of rheumatoid arthritis is infrequent and has been previously reported to involve large joints such as the hip and knee joints. Here we report a case series of four patients presenting to the University of Michigan in 2015 with monoarticular rheumatoid arthritis, one with small and three with large joint involvement. Material and Methods: In total, four patients with monoarticular rheumatoid arthritis were treated in the Division of Rheumatology, University of Michigan...
December 2017: European Journal of Rheumatology
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