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https://www.readbyqxmd.com/read/28920498/an-update-on-biomarker-discovery-and-use-in-axial-spondyloarthritis
#1
Walter P Maksymowych
Evaluation of diagnosis, disease activity, and risk for joint damage all represent important unmet clinical needs in the management of axial spondyloarthritis that have been explored using biomarkers. Areas Covered: This review used the search terms biomarkers, ankylosing spondylitis, spondyloarthritis, spondyloarthropathy, pathogenesis, genetics, diagnostic tools, prognosis, to explore advances in biomarker development relevant to unmet clinical needs. Expert Commentary: Despite major advances in the identification of genetic risk markers, HLA-B*27 remains the only marker with clinical utility for diagnostic purposes...
September 16, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28919520/antibodies-against-citrullinated-alpha-enolase-peptides-in-primary-sjogren-s-syndrome
#2
Adrianos Nezos, Ilir Cinoku, Clio P Mavragani, Haralampos M Moutsopoulos
Citrullinated alpha enolase (CEP-1) has been designated as a major antigenic target of antibodies against citrullinated proteins (ACPA) in patients with rheumatoid arthritis (RA). Our aim is to determine the prevalence of anti-CEP-1 in a cohort of ACPA positive (ACPA+) primary Sjogren's syndrome (pSS) patients. Anti-CEP1 titers were determined by ELISA in sera from 15 ACPA+ and 45 ACPA- age/sex matched pSS; 12 ACPA+ RA patients and 30 healthy controls (HC). Increased anti-CEP-1 antibody titers were detected in nine out of the 15 (60%) ACPA+ pSS patients and 5 out of 12 (41...
September 14, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28918591/platform-model-describing-pharmacokinetic-properties-of-vc-mmae-antibody-drug-conjugates
#3
Matts Kågedal, Leonid Gibiansky, Jian Xu, Xin Wang, Divya Samineni, Shang-Chiung Chen, Dan Lu, Priya Agarwal, Bei Wang, Ola Saad, Neelima Koppada, Bernard M Fine, Jin Y Jin, Sandhya Girish, Chunze Li
Antibody-drug conjugates (ADCs) developed using the valine-citrulline-MMAE (vc-MMAE) platform, consist of a monoclonal antibody (mAb) covalently bound with a potent anti-mitotic toxin (MMAE) through a protease-labile vc linker. Recently, clinical data for a variety of vc-MMAE ADCs has become available. The goal of this analysis was to develop a platform model that simultaneously described antibody-conjugated MMAE (acMMAE) pharmacokinetic (PK) data from eight vc-MMAE ADCs, against different targets and tumor indications; and to assess differences and similarities of model parameters and model predictions, between different compounds...
September 16, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28911876/immunoglobulin-isotype-switching-of-antibodies-to-vimentin-is-associated-with-development-of-transplant-glomerulopathy-following-human-renal-transplantation
#4
Muthukumar Gunasekaran, Thin Thin Maw, Rowena Delos Santos, Surendra Shenoy, Jason Wellen, T Mohanakumar
BACKGROUND: Immune responses to tissue-restricted self-antigens are thought to play a role in chronic rejection after solid organ transplantation. De novo development of antibodies (Abs) to vimentin have been reported to be associated with interstitial fibrosis/tubular atrophy after kidney transplant, and it has been suggested that immunoglobulin isotype switching of Abs to vimentin may occur during this process. We aimed to determine the correlation between immunoglobulin isotype switching of Abs to vimentin and development of transplant glomerulopathy (TG) after kidney transplant, and to determine whether citrullinated modification of vimentin is required for de novo anti-vimentin development...
September 11, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28904640/short-term-dietary-methionine-supplementation-affects-one-carbon-metabolism-and-dna-methylation-in-the-mouse-gut-and-leads-to-altered-microbiome-profiles-barrier-function-gene-expression-and-histomorphology
#5
Isabelle R Miousse, Rupak Pathak, Sarita Garg, Charles M Skinner, Stepan Melnyk, Oleksandra Pavliv, Howard Hendrickson, Reid D Landes, Annie Lumen, Alan J Tackett, Nicolaas E P Deutz, Martin Hauer-Jensen, Igor Koturbash
BACKGROUND: Methionine, a central molecule in one-carbon metabolism, is an essential amino acid required for normal growth and development. Despite its importance to biological systems, methionine is toxic when administered at supra-physiological levels. The aim of this study was to investigate the effects of short-term methionine dietary modulation on the proximal jejunum, the section of the gut specifically responsible for amino acid absorption, in a mouse model. Eight-week-old CBA/J male mice were fed methionine-adequate (MAD; 6...
2017: Genes & Nutrition
https://www.readbyqxmd.com/read/28904082/a-relative-l-arginine-deficiency-contributes-to-endothelial-dysfunction-across-the-stages-of-the-menopausal-transition
#6
Jelena Klawitter, Kerry L Hildreth, Uwe Christians, Wendy M Kohrt, Kerrie L Moreau
Vascular endothelial function declines across the menopause transition in women. We tested the hypothesis that reduced availability of the endothelial nitric oxide synthase [eNOS] substrate L-arginine is an underlying mechanism to vascular endothelial dysfunction across menopause stages. Endothelial function (brachial artery flow-mediated dilation [FMD]) and plasma markers of L-arginine metabolism (citrulline, N(G)-mono-methyl-ւ-arginine [L-NMMA] asymmetric dimethylarginine [ADMA] and N(G)-N('G)-dimethyl-l-arginine [SDMA]), were measured in 129 women: 36 premenopausal (33 ± 7 years), 16 early- (49 ± 3 years) or 21 late- (50 ± 4 years) perimenopausal, and 21 early- (55 ± 3 years) or 35 late- (61 ± 4 years) postmenopausal...
September 2017: Physiological Reports
https://www.readbyqxmd.com/read/28899798/is-acpa-positivity-the-main-driver-for-rheumatoid-arthritis-treatment-pros-and-cons
#7
REVIEW
Stefano Alivernini, Mauro Galeazzi, Hagit Peleg, Barbara Tolusso, Elisa Gremese, Gianfranco Ferraccioli, Yaakov Naparstek
Rheumatoid Arthritis (RA) is an autoimmune chronic disease that is characterized by the positivity of various antibodies, the most specific being autoantibodies against citrullinated antigens (ACPA). Despite ACPA are not arthritogenic by themselves, ACPA positive individuals have high risk of RA development and ACPA positivity is associated with severe erosive phenotype and higher mortality rate compared to seronegative RA. Moreover, ACPA status is associated with favorable response to biologics targeting pathways involving autoantibody producing cells as B lymphocytes...
September 9, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28899001/a-role-for-autoantibodies-in-atherogenesis
#8
Rosebella A Iseme, Mark McEvoy, Brian Kelly, Linda Agnew, Frederick R Walker, Tonelle Handley, Christopher Oldmeadow, John Attia, Michael Boyle
An increased risk of cardiovascular disease (CVD) has long been recognized amongst people with autoimmune disease. It has been unclear whether this is due mainly to the ensuing treatment, particularly steroids, or whether some of this risk is due to the autoimmune process itself with subsequent inflammation. Indeed, a large body of evidence supports a role for chronic inflammation in atherogenesis, and autoantibodies have been identified as mediators in this complex inflammatory environment. Our aim is to carry out a systematic review of existing literature in order to formally establish the strength of the association between autoantibodies and atherosclerosis, amongst individuals without clinical autoimmune disease...
August 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28893245/age-dependent-redox-status-in-the-brain-stem-of-no-deficient-hypertensive-rats
#9
Miroslava Majzúnová, Zuzana Pakanová, Peter Kvasnička, Peter Bališ, Soňa Čačányiová, Ima Dovinová
BACKGROUND: The brain stem contains important nuclei that control cardiovascular function via the sympathetic nervous system (SNS), which is strongly influenced by nitric oxide. Its biological activity is also largely determined by oxygen free radicals. Despite many experimental studies, the role of AT1R-NAD(P)H oxidase-superoxide pathway in NO-deficiency is not yet sufficiently clarified. We determined changes in free radical signaling and antioxidant and detoxification response in the brain stem of young and adult Wistar rats during chronic administration of exogenous NO inhibitors...
September 11, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28892879/evaluation-of-anti-cyclic-citrullinated-peptide-autoantibodies-and-c-reactive-protein-in-common-autoimmune-skin-diseases-with-and-without-arthritis
#10
Bandana Kumari, Pawan Kumar, Radha Krishna Prasad Chaudhary
INTRODUCTION: Anti-Cyclic Citrullinated Peptides (CCPs) are a well known diagnostic and prognostic noble marker for rheumatoid arthritis. C-Reactive Protein (CRP) is an acute phase protein whose level rises in response to inflammation. AIM: This study was undertaken to show the role of the two markers (anti-CCPs and CRP) in autoimmune skin disorder and their association with associated arthritis in these disorder. MATERIALS AND METHODS: Serum anti-CCP antibodies and CRP was measured in 50 patients of autoimmune skin disease of which 28 were of psoriasis, 12 of Systemic Lupus Erythematosus (SLE) and 10 of Pemphigus Vulgaris (PV)...
July 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28889152/anti-carbamylated-protein-antibodies-in-rheumatoid-arthritis-patients-and-their-association-with-rheumatoid-factor
#11
Maizatul A Othman, Wan Syamimee W Ghazali, Wan Zuraida W A Hamid, Kah K Wong, Nurul K Yahya
To evaluate levels of anti-carbamylated protein (anti-CarP) antibodies in rheumatoid arthritis (RA) patients and to determine their association with serological parameters and disease activity. Methods: A cross-sectional study involving 105 multiethnic RA patients (48 rheumatoid factor [RF]-positive and 57 RF-negative patients) was conducted at Hospital Universiti Sains Malaysia, Kelantan, Malaysia, from January 2015 to February 2016. Fifty healthy controls (HCs) were included. C-reactive protein (CRP), RF, anti-cyclic citrullinated peptide (anti-CCP) and anti-CarP antibodies were measured...
September 2017: Saudi Medical Journal
https://www.readbyqxmd.com/read/28886586/a-murine-ig-light-chain-transgene-reveals-igkv3-gene-contributions-to-anti-collagen-types-iv-and-ii-specificities
#12
Amy G Clark, Inge M Worni-Schudel, Francesca M Korte, Mary H Foster
A subset of autoimmune diseases result from autoantibodies targeting epitopes on matrix collagen. The most extensively studied are anti-glomerular basement membrane glomerulonephritis (or its systemic counterpart Goodpasture's disease) that destroys kidneys and lungs, and rheumatoid arthritis that leads to disabling arthritis. Autoantibodies in these disorders bind evolutionarily conserved conformational epitopes on the noncollagenous domain 1 (NC1) of the alpha3 chain of type IV [alpha3(IV)NC1] collagen in glomerular and alveolar basement membranes, and on native or citrullinated type II collagen (CII) in joint cartilage, respectively...
September 5, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28882619/variable-domain-glycosylation-of-acpa-igg-a-missing-link-in-the-maturation-of-the-acpa-response
#13
Ayla C Kempers, Lise Hafkenscheid, Hans Ulrich Scherer, René E M Toes
Anti-citrullinated Protein Antibodies (ACPA) are excellent markers for Rheumatoid arthritis (RA) and are postulated to have a pathogenic role in the disease process. A multistep model for the evolution of the ACPA response in RA was proposed in which an initial break of tolerance causes, as "first hit", "silent" production of ACPA without any clinical symptoms. The model further proposes that the ACPA immune response matures upon a certain (unknown) trigger, a "second hit", which leads to epitope spreading, an increase in ACPA titres and extended isotype usage before clinical RA manifestations...
September 4, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28881747/excessive-matrix-metalloprotease-mediated-degradation-of-interstitial-tissue-type-i-collagen-independently-predicts-short-term-survival-in-an-observational-study-of-postmenopausal-women-diagnosed-with-cancer
#14
Nicholas Willumsen, Cecilie L Bager, Stephanie N Kehlet, Katrine Dragsbaek, Jesper S Neergaard, Henrik B Hansen, Anne-Christine Bay-Jensen, Diana J Leeming, Allan Lipton, Claus Christiansen, Morten Karsdal
Extensive tissue remodeling mediated by matrix metalloproteases (MMPs) is an important part of cancer. The aim of this study was to investigate whether serum biomarkers reflecting MMP-mediated degradation of type I collagen (C1M), type IV collagen (C4M) and citrullinated vimentin (VICM) were predictive of cancer-specific mortality. Between 1999 and 2001, 5855 Danish postmenopausal women participated in The Prospective Epidemiologic Risk Factor (PERF I) study. Demographics and serum samples were collected at enrolment...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877324/t786c-mutation-in-the-endothelial-nitric-oxide-synthase-gene-in-patients-with-primary-osteonecrosis
#15
Amir M Khan, Joshua Choi, Richard A Freiberg, Charles J Glueck, Naila Goldenberg, Ping Wang
Mutations in the T786C endothelial nitric oxide synthase gene (eNOS) are associated with osteonecrosis and Prinzmetal's angina. Nitric oxide is necessary for bone health and ameliorates Prinzmetal's angina. This study compared mutations of T786C eNOS in 146 patients with primary osteonecrosis, 114 patients with Prinzmetal's angina, and 83 normal control subjects. Patients with osteonecrosis had more mutant eNOS alleles than control subjects (42% vs 22%, respectively; P<.0001) but had the same number of mutant alleles as patients with Prinzmetal's angina (42% vs 41%, respectively; P=...
September 6, 2017: Orthopedics
https://www.readbyqxmd.com/read/28873598/-1-h-hr-mas-nmr-based-metabolomics-study-of-different-persimmon-cultivars-diospyros-kaki-during-fruit-development
#16
Alan Diego da Conceição Santos, Flávia Aparecida Fonseca, Lívia Macedo Dutra, Maria de Fátima Costa Santos, Leociley Rocha Alencar Menezes, Francinete Ramos Campos, Noemi Nagata, Ricardo Ayub, Andersson Barison
(1)H HR-MAS NMR spectroscopy was used to track the metabolic changes throughout the whole development of astringent ('Giombo') and non-astringent ('Fuyu') cultivars of persimmon (Diospyros kaki). The NMR data revealed the low concentration of amino acids (threonine, alanine, citrulline and GABA) and organic acids (malic acid). In addition, the signals of carbohydrates (sucrose, glucose and fructose) seemed to play the most important role in the fruit development. In both cultivars, the growth was characterized by fluctuating sucrose concentration along with a constant increase in both glucose and fructose...
January 15, 2018: Food Chemistry
https://www.readbyqxmd.com/read/28871954/-elevated-serum-il-25-levels-in-rheumatoid-arthritis-patients-with-bone-erosion-and-interstitial-lung-disease
#17
Jinyue Lu, Minglian DA, Yuchen Feng, Yuanyuan Liu, Sigong Zhang, Haili Shen
Objective To detect the serum levels of IL-25 and IL-17 in rheumatoid arthritis (RA) patients and investigate the potential relationship with bone erosion and concomitant interstitial lung disease (ILD). Methods The study enrolled a total of 117 RA patients and 56 healthy subjects as controls. The serum levels of IL-25 and IL-17 were determined by ELISA, and rheumatoid factor (RF) was detected by turbidimetric immunoassay, anticyclic citrullinated peptide (anti-CCP) antibody as well as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also tested...
August 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28870033/-the-expression-and-clinical-significance-of-proprotein-convertase-subtilisin-kexin-9-in-rheumatoid-arthritis
#18
Q Du, X J Yu, H J Li, S Q Guan, Z Y Zhang, Y F Mei
Objective: To assess the expression and significance of proprotein convertase subtilisin kexin 9 (PCSK9) in patients with rheumatoid arthritis (RA). Methods: Sixty-five RA patients and forty-seven healthy controls were recruited in this study. The body mass index (BMI) and serum total cholesterol(TC), triglyceride(TG), high density lipoprotein(HDL), lipoprotein a, low density lipoprotein(LDL), very low density lipoprotein(VLDL), apolipoprotein A(ApoA), apolipoprotein B(ApoB) and the ratio of LDL-C/HDL-C were tested...
September 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28868581/in-human-brain-ornithine-transcarbamylase-otc-immunoreactivity-is-strongly-expressed-in-a-small-number-of-nitrergic-neurons
#19
Hans-Gert Bernstein, Hendrik Dobrowolny, Gerburg Keilhoff, Johann Steiner
There is recent evidence for ornithine transcarbamylase (OTC) expression in adult human brain. We decided to immunocytochemically map OTC throughout brain, and to further characterize OTC-immunopositive neurons. By using double immunolabeling technique for OTC and neuronal nitric oxide synthase (nNOS) OTC protein expression was revealed in a small subset of nitrergic (nNOS) neurons. Since citrulline (the reaction product of OTC) enhances the bioavailability of L-arginine, the substrate of nNOS, it is conceivable that OTC activity supports NO production in nitrergic neurons...
September 3, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28867511/glutamine-and-citrulline-concentrations-reflect-nitric-oxide-synthesis-in-the-human-nervous-system
#20
I Pérez-Neri, J Ramírez-Bermúdez, C Ojeda-López, S Montes, J L Soto-Hernández, C Ríos
INTRODUCTION: Although citrulline is produced by nitric oxide (NO) synthase upon activation of the NMDA glutamate receptor, nitrite and nitrate (NOx) concentration is considered the best marker of NO synthesis, as citrulline is also metabolised by other enzymes. This study analyses the correlation between human cerebrospinal fluid NOx and citrulline concentrations in order to determine the extent to which citrulline reflects NO synthesis and glutamatergic neurotransmission. METHODS: Participants were patients with acute neurological diseases undergoing lumbar puncture (n=240)...
August 31, 2017: Neurología: Publicación Oficial de la Sociedad Española de Neurología
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