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https://www.readbyqxmd.com/read/29333561/pharmacokinetics-of-the-b-cell-lymphoma-2-bcl-2-inhibitor-venetoclax-in-female-subjects-with-systemic-lupus-erythematosus
#1
Mukul Minocha, Jiewei Zeng, Jeroen K Medema, Ahmed A Othman
BACKGROUND AND OBJECTIVE: Venetoclax is an oral selective Bcl-2 inhibitor approved for the treatment of patients with chronic lymphocytic leukemia with 17p deletion. Mechanistic and preclinical evidence warranted evaluation of venetoclax for the treatment of systemic lupus erythematosus (SLE). This work characterized the pharmacokinetics of venetoclax in female subjects with SLE. METHODS: Single (10-500 mg) and multiple (30-600 mg) escalating doses of venetoclax or matching placebo were evaluated using randomized, double-blind, placebo-controlled designs (6 active and 2 placebo per dose with 73 unique SLE patients enrolled, 25 of whom enrolled twice)...
January 15, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29330755/-lymphoma-in-rheumatic-diseases
#2
REVIEW
A Rubbert-Roth, J T Bittenbring, G Assmann
Various systemic inflammatory diseases, such as rheumatoid arthritis (RA), Sjögren's syndrome and systemic lupus erythematosus (SLE) are associated with an increased risk for the development of lymphomas. Studies on patients with RA and Sjögren's syndrome have shown that there is a clear association of the incidence of lymphoma with the severity and activity of the disease and lymphomas in particular are diseases which preferentially occur in immunosuppressed patients; therefore, knowledge of the different lymphoma subtypes, their prognosis and treatment options are important for rheumatologists...
October 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/29330524/nf-%C3%AE%C2%BAb-inducing-kinase-is-a-therapeutic-target-for-systemic-lupus-erythematosus
#3
Hans D Brightbill, Eric Suto, Nicole Blaquiere, Nandhini Ramamoorthi, Swathi Sujatha-Bhaskar, Emily B Gogol, Georgette M Castanedo, Benjamin T Jackson, Youngsu C Kwon, Susan Haller, Justin Lesch, Karin Bents, Christine Everett, Pawan Bir Kohli, Sandra Linge, Laura Christian, Kathy Barrett, Allan Jaochico, Leonid M Berezhkovskiy, Peter W Fan, Zora Modrusan, Kelli Veliz, Michael J Townsend, Jason DeVoss, Adam R Johnson, Robert Godemann, Wyne P Lee, Cary D Austin, Brent S McKenzie, Jason A Hackney, James J Crawford, Steven T Staben, Moulay H Alaoui Ismaili, Lawren C Wu, Nico Ghilardi
NF-κB-inducing kinase (NIK) mediates non-canonical NF-κB signaling downstream of multiple TNF family members, including BAFF, TWEAK, CD40, and OX40, which are implicated in the pathogenesis of systemic lupus erythematosus (SLE). Here, we show that experimental lupus in NZB/W F1 mice can be treated with a highly selective and potent NIK small molecule inhibitor. Both in vitro as well as in vivo, NIK inhibition recapitulates the pharmacological effects of BAFF blockade, which is clinically efficacious in SLE...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29329127/cutis-laxa-acquisita-after-urticarial-vasculitis-in-sle-patients
#4
Kimberly B Golisch, Silvija P Gottesman, Patricia Ferrer, Keliegh S Culpepper
Cutis laxa is a rare connective tissue disease involving damage to dermal elastic fibers creating a clinical appearance of loose, sagging skin. The condition can be either acquired or genetic. Autoimmune diseases, neoplasms, infections, and medications have been proposed as the cause of, or in association with, the acquired form. In nearly 50% of cases, erythematous plaques present before the onset of cutis laxa. Separately, urticarial vasculitis and systemic lupus erythematosus have been linked to cutis laxa acquisita...
January 11, 2018: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/29328521/the-central-vein-sign-differentiates-ms-from-cns-inflammatory-vasculopathies
#5
Pietro Maggi, Martina Absinta, Matteo Grammatico, Luisa Vuolo, Giacomo Emmi, Giovanna Carlucci, Gregorio Spagni, Alessandro Barilaro, Anna Maria Repice, Lorenzo Emmi, Domenico Prisco, Vittorio Martinelli, Roberta Scotti, Niloufar Sadeghi, Gaetano Perrotta, Pascal Sati, Bernard Dachy, Daniel S Reich, Massimo Filippi, Luca Massacesi
OBJECTIVES: In multiple sclerosis (MS), MRI is a sensitive tool for detecting white matter lesions, but its diagnostic specificity is still suboptimal; ambiguous cases are frequent in clinical practice. Detection of perivenular lesions in the brain (the "central vein sign") improves the pathological specificity of MS diagnosis, but comprehensive evaluation of this MRI biomarker in MS-mimicking inflammatory and/or autoimmune diseases, such as CNS inflammatory vasculopathies, is missing...
January 12, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29328507/genetics-of-immune-mediated-inflammatory-diseases
#6
REVIEW
Trixy David, Stephanie Ling, Anne Barton
Immune-mediated inflammatory diseases (IMIDs) are characterised by dysregulation of the normal immune response, which leads to inflammation. Together, they account for a high disease burden in the population, given that they are usually chronic conditions with associated co-morbidities. Examples include systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease and type 1 diabetes. Since the advent of genome-wide association studies, evidence of considerable genetic overlap in the loci predisposing to a wide range of IMIDs has emerged...
January 12, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29328425/bioinformatics-analysis-of-the-cdk2-functions-in-neuroblastoma
#7
Lijuan Bo, Bo Wei, Zhanfeng Wang, Daliang Kong, Zheng Gao, Zhuang Miao
The present study aimed to elucidate the potential mechanism of cyclin-dependent kinase 2 (CDK2) in neuroblastoma progression and to identify the candidate genes associated with neuroblastoma with CDK2 silencing. The microarray data of GSE16480 were obtained from the gene expression omnibus database. This dataset contained 15 samples: Neuroblastoma cell line IMR32 transfected with CDK2 shRNA at 0, 8, 24, 48 and 72 h (n=3 per group; total=15). Significant clusters associated with differentially expressed genes (DEGs) were identified using fuzzy C‑Means algorithm in the Mfuzz package...
December 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29325582/urinary-angiostatin-cxcl4-and-vcam-1-as-biomarkers-of-lupus-nephritis
#8
Chi Chiu Mok, Samar Soliman, Ling Yin Ho, Fatma A Mohamed, Faten Ismail Mohamed, Chandra Mohan
BACKGROUND: The aim was to study urinary angiostatin, CXC chemokine ligand 4 (CXCL4) and vascular cell adhesion molecule-1 (VCAM-1) as biomarkers of renal disease in systemic lupus erythematosus (SLE). METHOD: Patients who fulfilled ≥ 4 American College of Rheumatology (ACR) criteria for SLE with active renal, active non-renal or inactive disease, and a group of healthy controls were studied. Urine samples were assayed for angiostatin, CXCL4 and VCAM-1 by ELISA, and normalized by creatinine...
January 11, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29325492/illness-perception-is-significantly-determined-by-depression-and-anxiety-in-systemic-lupus-erythematosus
#9
K Nowicka-Sauer, A Hajduk, H Kujawska-Danecka, D Banaszkiewicz, Ż Smoleńska, Z Czuszyńska, J Siebert
Objectives Illness perception is a cognitive representation influencing physical and psychological functioning and adherence in patients with rheumatic disease. Studies exploring illness perception in systemic lupus erythematosus (SLE) are still scarce and none of them have investigated factors determining illness perception. We aimed to assess illness perception and to identify psychological, clinical and sociodemographic factors that might influence illness perception in SLE. Methods The study involved 80 patients with SLE (87...
January 1, 2018: Lupus
https://www.readbyqxmd.com/read/29325308/-opportunistic-infection-in-systemic-lupus-erythematosus-patients-the-disease-spectrum-and-the-characteristics-of-peripheral-lymphocyte-subsets
#10
L Qin, Z F Qiu, J Xie, T R Geng, J L Zhao, L Wan, T S Li
Objective: To investigate the common opportunistic infections and the characteristics of peripheral lymphocyte subsets in patients with systemic lupus erythematosus (SLE). Methods: From December 2013 to December 2016, peripheral lymphocyte subsets were consecutively detected by flow cytometry in treated SLE patients with or without opportunistic infections (OIs) . The lymphocyte subsets in healthy donors were used as normal control group. Results: A total of 145 treated SLE patients were enrolled including 108 with OIs and 37 without OIs...
January 1, 2018: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/29324237/dna-induction-of-mdm2-promotes-proliferation-of-human-renal-mesangial-cells-and-alters-peripheral-b-cells-subsets-in-pediatric-systemic-lupus-erythematosus
#11
Chen-Xing Zhang, Ji Chen, Li Cai, Jing Wu, Jia-Yuan Wang, Lan-Fang Cao, Wei Zhou, Tong-Xin Chen
The study is aimed to investigate the role of MDM2 in the pathogenesis of lupus nephritis (LN) in pediatric SLE (pSLE). We confirmed that MDM2 expression was increased in peripheral blood mononuclear cells (PBMCs) as well as renal specimen of SLE compared with that of controls by western blot and immunofluorescence staining. Percentage of apoptotic and necrotic CD4+T, CD8+T and B cells were detected by flow cytometry respectively and levels of plasma cell free DNA (cfDNA) were quantified in SLE and healthy controls (HC)...
January 8, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29323451/microvascular-involvement-in-systemic-sclerosis-and-systemic-lupus-erythematosus
#12
Didem Saygin, Kristin Highland, Adriano R Tonelli
Microvascular changes play central roles in the pathophysiology of systemic sclerosis (SSc) and systemic lupus erythematosus (SLE), and represent major causes of morbidity and mortality in these patients. Therefore, clinical tools that can assess the microvasculature are of great importance both at the time of diagnosis and follow up of these cases. These tools include capillaroscopy, laser imaging techniques, infrared thermography and iontophoresis. In this review, we examined the clinical manifestations and pathobiology of microvascular involvement in SSc and SLE as well as the methodologies used to evaluate the microvasculature...
January 11, 2018: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/29322712/a-cross-sectional-study-of-cardiovascular-involvement-in-systemic-lupus-erythematosus-in-an-urban-indian-tertiary-care-centre-with-emphasis-on-2-d-echocardiography
#13
Seema Kini, Chetan Vekhande, Vikram Londhey
Background: Cardiovascular manifestations are responsible for considerable morbidity and mortality in patients with SLE. A wide range of manifestations due to active lupus, like pericarditis, valvular affection, myocarditis, and less commonly pulmonary hypertension, are described. This study was undertaken to study cardiovascular manifestations in SLE, with a focus on echocardiography findings, in an urban Indian setting. Methodology: Fifty consecutive cases of SLE following up in the Rheumatology Clinic of TNMC and BYL Nair Charitable hospital, an Indian tertiary care hospital were studied...
November 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/29321925/lupus-pneumonitis-presenting-with-high-titre-of-anti-ro-antibody
#14
Mei-Chuan Chen, Yueh-Lin Wu, Kai-Ling Lee, Kevin S Lai, Chi-Li Chung
Lupus pneumonitis carries high mortality and is a rare manifestation of systemic lupus erythematosus (SLE). However, it is difficult to diagnose and is often mistaken as pneumonia, alveolar haemorrhage, or organizing pneumonia. Previous studies demonstrated that serum anti-Ro antibodies are elevated more frequently in SLE patients with pneumonitis than in those without. We report a 21-year-old female who was newly diagnosed as having SLE with nephritis and who suddenly developed right lung opacity and rapidly progressed to severe hypoxaemia despite the use of broad-spectrum antibiotics...
January 2018: Respirology Case Reports
https://www.readbyqxmd.com/read/29321815/circulating-plasma-microrna-profiling-in-patients-with-polymyositis-dermatomyositis-before-and-after-treatment-mirna-may-be-associated-with-polymyositis-dermatomyositis
#15
Takuya Hirai, Keigo Ikeda, Hiroshi Tsushima, Maki Fujishiro, Kunihiro Hayakawa, Yuko Yoshida, Shinji Morimoto, Ken Yamaji, Yoshinari Takasaki, Kenji Takamori, Naoto Tamura, Iwao Sekigawa
Background: MicroRNAs (miRNAs) are involved in the regulation of key biological processes and have been implicated in various diseases, including autoimmune disorders. The pathogenesis of polymyositis (PM) and dermatomyositis (DM) is considered to be mediated by autoimmune reactions. To determine miRNA role in the development and progression of PM and DM, we performed plasma miRNA profiling in PM/DM patients before and after treatment. Methods: Total RNA was isolated from plasma of 10 patients before and after treatment with prednisolone, or, in case of prednisolone resistance or complications, with the combination of calcineurin inhibitors (cyclosporine or tacrolims) and/or pulse intravenous cyclophosphamide...
2018: Inflammation and Regeneration
https://www.readbyqxmd.com/read/29321714/cavum-vergae-liability-and-steroid-treatment-manic-episode-brain-imaging-findings-and-clinical-follow-up-of-a-systemic-lupus-erythematosus-case
#16
Emre Misir, İbrahim Tolga Binbay, Bilge Targitay, Hidayet Ece Arat, Gerçek Can, Köksal Alptekin
Systemic lupus erythematosus (SLE) or Lupus is a chronic and idiopathic autoimmune connective tissue disease that involves several organs and organ systems. SLE may lead to a group of psychiatric manifestations, including delirium, anxiety disorders, cognitive dysfunction, mood disorders, and psychosis, which are caused by organic or non-organic factors. In addition, it is thought that the most common cause of neuropsychiatric lupus is corticosteroid use; central nervous system involvement and inflammatory processes also have an important role in the development of psychiatric manifestations...
December 2017: Noro Psikiyatri Arsivi
https://www.readbyqxmd.com/read/29321445/negative-regulation-of-b-cell-responses-and-self-tolerance-to-rna-related-lupus-self-antigen
#17
Takeshi Tsubata
The antibody response to RNA-related antigens such as Sm/RNP requires the endosomal RNA sensor TLR7, and this process is crucial in the development of systemic lupus erythematosus at least in animal models. The inhibitory B cell receptor CD72 is unique because it recognizes Sm/RNP and specifically inhibits the activation of Sm/RNP-reactive B cells by activating SH2-containing protein tyrosine phosphatase 1 (SHP-1). In the normal immune system, Sm/RNP-reactive B cells are tolerized by a unique mechanism that probably involves SHP-1...
2018: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/29321410/successful-management-of-pregnancy-in-a-patient-with-systemic-lupus-erythematosus-associated-pulmonary-arterial-hypertension
#18
Akio Kawabe, Kazuhisa Nakano, Yukiyo Aiko, Satoshi Aramaki, Takeshi Onoue, Dan Okura, Yoshiya Tanaka
Pregnancy in women with systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH) remains a high risk. We successfully managed a pregnancy in a patient with SLE-PAH. A 31-year-old pregnant woman with SLE-PAH had worsening PAH and SLE flare-up during pregnancy and a sudden increase in pulmonary arterial pressure after delivery. SLE-PAH was controlled by continuous intravenous epoprostenol and inhaled nitric oxide therapy combined with high-dose corticosteroids under close hemodynamic monitoring...
January 11, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29321042/type-i-ifn-signature-in-childhood-onset-systemic-lupus-erythematosus-a-conspiracy-of-dna-and-rna-sensing-receptors
#19
M Javad Wahadat, Iris L A Bodewes, Naomi I Maria, Cornelia G van Helden-Meeuwsen, Annette van Dijk-Hummelman, Eline C Steenwijk, Sylvia Kamphuis, Marjan A Versnel
BACKGROUND: Childhood-onset systemic lupus erythematosus (cSLE) is an incurable multi-systemic autoimmune disease. Interferon type I (IFN-I) plays a pivotal role in the pathogenesis of SLE. The objective of this study was to assess the prevalence of the IFN-I signature and the contribution of cytosolic nucleic acid receptors to IFN-I activation in a cohort of primarily white cSLE patients. METHODS: The IFN-I score (positive or negative), as a measure of IFN-I activation, was assessed using real-time quantitative PCR (RT-PCR) expression values of IFN-I signature genes (IFI44, IFI44L, IFIT1, Ly6e, MxA, IFITM1) in CD14+ monocytes of cSLE patients and healthy controls (HCs)...
January 10, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29320976/the-mediational-role-of-helplessness-in-psychological-outcomes-in-systemic-lupus-erythematosus
#20
S D Mills, D Azizoddin, S Gholizadeh, G Z Racaza, P M Nicassio
Objective Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can result in disability and psychological distress. Although pain has been associated with depressive symptomatology and stress in SLE, a paucity of theoretical models have been used to explain the relationship between pain and psychological distress in this population. Thus, the present study examined helplessness as a mediator of the relationship between pain and psychological distress among patients with SLE. Methods Multiple mediation analysis was used to examine the hypothesis that learned helplessness mediates the relationship between pain and symptoms of anxiety, depression, and stress in a sample of patients with SLE ( N = 136) receiving medical care at Cedars Sinai Medical Center...
January 1, 2018: Lupus
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