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Citrulline

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https://www.readbyqxmd.com/read/29330439/induction-of-protein-citrullination-and-auto-antibodies-production-in-murine-exposed-to-nickel-nanomaterials
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/29305240/a-pilot-study-of-a-non-invasive-oral-nitrate-stable-isotopic-method-suggests-that-arginine-and-citrulline-supplementation-increases-whole-body-no-production-in-tanzanian-children-with-sickle-cell-disease
#12
Alphonce I Marealle, Mario Siervo, Sara Wassel, Les Bluck, Andrew M Prentice, Omary Minzi, Philip Sasi, Appolinary Kamuhabwa, Deogratias Soka, Julie Makani, Sharon E Cox
BACKGROUND: Low bioavailability of nitric oxide (NO) is implicated in the pathophysiology of sickle cell disease (SCD). We designed a nested pilot study to be conducted within a clinical trial testing the effects of a daily ready-to-use supplementary food (RUSF) fortified with arginine (Arg) and citrulline (Citr) vs. non-fortified RUSF in children with SCD. The pilot study evaluated 1) the feasibility of a non-invasive stable isotope method to measure whole-body NO production and 2) whether Arg+Citr supplementation was associated with increased whole-body NO production...
January 2, 2018: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29304522/the-pathophysiological-role-of-neutrophil-extracellular-traps-in-inflammatory-diseases
#13
Aldo Bonaventura, Luca Liberale, Federico Carbone, Alessandra Vecchié, Candela Diaz-Cañestro, Giovanni G Camici, Fabrizio Montecucco, Franco Dallegri
Neutrophil pathogen-killing mechanism termed neutrophil extracellular traps (NETs) has been recently identified. NETs consist of chromatin and histones along with serine proteases and myeloperoxidase and are induced by a great variety of infectious and non-infectious stimuli. NETosis is a kind of programmed neutrophil death characterized by chromatin decondensation and release of nuclear granular contents, mainly driven by peptidylarginine deiminase 4 citrullination of histones. Although classically related to the protection against infectious pathogens, nowadays NETs have been described as a player of several pathophysiological processes...
January 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29303709/cost-effectiveness-of-early-treatment-of-acpa-positive-rheumatoid-arthritis-patients-with-abatacept
#14
Aljoscha S Neubauer, Christof Minartz, Kirsten H Herrmann, Christoph G O Baerwald
OBJECTIVES: Studies have reported that the presence of elevated anti-citrullinated protein antibodies (ACPA)/RF levels, together with joint erosions, is associated with higher disease burden in terms of disability and mortality in rheumatoid arthritis (RA). Abatacept has been shown to be effective in this patient population with favourable comparative data against adalimumab. However, few studies have investigated the cost-effectiveness of abatacept in this population to similar treatments such as TNFs...
December 15, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29298553/conserved-citrullinating-exoenzymes-in-porphyromonas-species
#15
G Gabarrini, M A Chlebowicz, M E Vega Quiroz, A C M Veloo, J W A Rossen, H J M Harmsen, M L Laine, J M van Dijl, A J van Winkelhoff
Porphyromonas gingivalis is one of the major oral pathogens implicated in the widespread inflammatory disorder periodontitis. Moreover, in recent years, P. gingivalis has been associated with the autoimmune disease rheumatoid arthritis. The peptidylarginine deiminase enzyme of P. gingivalis (PPAD) is a major virulence factor that catalyzes the citrullination of both bacterial and host proteins, potentially contributing to production of anticitrullinated protein antibodies. Considering that these antibodies are very specific for rheumatoid arthritis, PPAD appears to be a link between P...
December 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/29290168/the-economic-burden-of-acpa-positive-status-among-patients-with-rheumatoid-arthritis
#16
Jason Shafrin, Mahlet Gizaw Tebeka, Kwanza Price, Chad Patel, Kaleb Michaud
BACKGROUND: Anticitrullinated protein antibodies (ACPAs) are serological biomarkers associated with early, rapidly progressing rheumatoid arthritis (RA), including more severe disease and joint damage. ACPA testing has become a routine tool for RA diagnosis and prognosis. Furthermore, treatment efficacy has been shown to vary by ACPA-positive status. However, it is not clear if the economic burden of patients with RA varies by ACPA status. OBJECTIVE: To determine if the economic burden of RA varies by patient ACPA status...
January 2018: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/29287593/upregulation-of-citrullination-pathway-from-autoimmune-to-idiopathic-lung-fibrosis
#17
Katerina D Samara, Athina Trachalaki, Eliza Tsitoura, Anastasios V Koutsopoulos, Eleni D Lagoudaki, Ismini Lasithiotaki, George Margaritopoulos, Panagiotis Pantelidis, Eleni Bibaki, Nikolaos M Siafakas, Nikolaos Tzanakis, Athol U Wells, Katerina M Antoniou
BACKGROUND: Increased protein citrullination and peptidylarginine deiminases (PADIs), which catalyze the citrullination process, are central in Rheumatoid arthritis pathogenesis and probably involved in the initial steps towards autoimmunity. Approximately, 10% of RA patients develop clinically significantly ILD. A possible shared role of protein citrullination in rheumatoid arthritis associated interstitial lung disease (RA-ILD), and idiopathic pulmonary fibrosis (IPF) pathogenesis remains unclear...
December 29, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29286527/experience-of-correcting-endothelial-dysfunction-in-children-residents-of-radioactively-contaminated-areas-by-nitric-oxide-potential-donator-citrulline
#18
Ye I Stepanova, I Ye Kolpakov, V M Zygalo, V Yu Vdovenko, V H Kondrashova, O S Leonovich, V V Kryzhanivska
OBJECTIVE: to determine the effectiveness of citrulline use for correcting endothelial dysfunction in children resi dents of radioactively contaminated areas. MATERIALS AND METHODS: A group of children residents of radioactively contaminated areas with the presence of clinical and paraclinical signs of endothelial dysfunction was selected to assess the effectiveness of correcting endothelial dysfunction by the usage of NO potential donator - citrulline according to the data of selective screen ing...
December 2017: Problemy Radiat︠s︡iĭnoï Medyt︠s︡yny Ta Radiobiolohiï
https://www.readbyqxmd.com/read/29282796/disease-causing-mutations-in-the-promoter-and-enhancer-of-the-ornithine-transcarbamylase-gene
#19
Yoon J Jang, Abigail L LaBella, Timothy P Feeney, Nancy Braverman, Mendel Tuchman, Hiroki Morizono, Nicholas Ah Mew, Ljubica Caldovic
The ornithine transcarbamylase (OTC) gene is on the X chromosome and its product catalyzes the formation of citrulline from ornithine and carbamylphosphate in the urea cycle. About 10-15% of patients, clinically diagnosed with OTC deficiency (OTCD), lack identifiable mutations in the coding region or splice junctions of the OTC gene on routine molecular testing. We collected DNA from such patients via retrospective review and by prospective enrollment. In nine of 38 subjects (24%), we identified a sequence variant in the OTC regulatory regions...
December 27, 2017: Human Mutation
https://www.readbyqxmd.com/read/29282299/an-anti-gdnf-family-receptor-alpha-1-gfra1-antibody-drug-conjugate-for-the-treatment-of-hormone-receptor-positive-breast-cancer
#20
Sunil Bhakta, Lisa M Crocker, Yvonne Chen, Meredith Hazen, Melissa M Schutten, Dongwei Li, Coenraad Kuijl, Rachana Ohri, Fiona Zhong, Kirsten Achilles Poon, Mary Ann T Go, Eric Cheng, Robert Piskol, Ron Firestein, Aimee Fourie-O'Donohue, Katherine R Kozak, Helga Raab, Jo-Anne Hongo, Deepak Sampath, Mark S Dennis, Richard H Scheller, Paul Polakis, Jagath R Junutula
Luminal A (hormone receptor-positive) breast cancer constitutes 70% of total breast cancer patients. In an attempt to develop a targeted therapeutic for this cancer indication, we have identified and characterized Glial cell line-Derived Neurotrophic Factor (GDNF) Family Receptor Alpha 1 (GFRA1) antibody-drug conjugates (ADC) using a cleavable valine-citrulline-MMAE (vcMMAE) linker-payload. RNAseq and immunohistochemistry analysis confirmed the abundant expression of GFRA1 in luminal A breast cancer tissues, while minimal or no expression was observed in most normal tissues...
December 27, 2017: Molecular Cancer Therapeutics
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