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Arthritis and gene therapy

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https://www.readbyqxmd.com/read/29045979/-changes-of-serum-krebs-von-den-lungen-6-levels-in-interstitial-lung-disease-associated-with-dermatomyositis-and-secondary-sj%C3%A3-gren-s-syndrome-a-case-report
#1
J F Yu, Y B Jin, J He, Y An, Z G Li
Interstitial lung diseases (ILDs) are a diverse group of pulmonary disorders characterized by various patterns of inflammation and fibrosis in the interstitium of the lung. The underlying pathogenesis of ILDs is complex and associated with multiple rheumatologic conditions, such as systemic sclerosis, rheumatoid arthritis, pollymyositis and dermatomyositis, Sjögren's syndrome, and systemic lupus erythematosus. As the disease progresses, excessive pulmonary fibrosis impairs alveolar gas exchange and damages pulmonary function...
October 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/29041934/h-syndrome-5-new-cases-from-the-united-states-with-novel-features-and-responses-to-therapy
#2
Jessica L Bloom, Clara Lin, Lisa Imundo, Stephen Guthery, Shelly Stepenaskie, Csaba Galambos, Amy Lowichik, John F Bohnsack
BACKGROUND: H Syndrome is an autosomal recessive disorder characterized by cutaneous hyperpigmentation, hypertrichosis, and induration with numerous systemic manifestations. The syndrome is caused by mutations in SLC29A3, a gene located on chromosome 10q23, which encodes the human equilibrative transporter 3 (hENT3). Less than 100 patients with H syndrome have been described in the literature, with the majority being of Arab descent, and only a few from North America. CASE PRESENTATION: Here we report five pediatric patients from three medical centers in the United States who were identified to have H syndrome by whole exome sequencing...
October 17, 2017: Pediatric Rheumatology Online Journal
https://www.readbyqxmd.com/read/29030294/type-i-interferon-pathway-activation-in-copa-syndrome
#3
Stefano Volpi, Jessica Tsui, Marcello Mariani, Claudia Pastorino, Roberta Caorsi, Oliviero Sacco, Angelo Ravelli, Anthony K Shum, Marco Gattorno, Paolo Picco
Mutations of the COPA gene cause an immune dysregulatory disease characterised by polyarticular arthritis and progressive interstitial lung disease with pulmonary haemorrhages. We report the case of a young girl that presented at age 3 with polyarticular arthritis, chronic cough and high titer rheumatoid factor. Radiologic imaging showed interstitial lung disease with tree-in-a-bud nodules and air-filled cysts. Targeted genetic analysis of COPA gene showed the reported c.698G>A mutation. The patient was lost to follow up for 3years during which therapy was discontinued with the development of joint damage and deformities...
October 10, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28987932/ethyl-pyruvate-ameliorates-inflammatory-arthritis-in-mice
#4
Seung Min Jung, Jaeseon Lee, Seung Ye Baek, Juhyun Lee, Se Gwang Jang, Seung-Min Hong, Jin-Sil Park, Mi-La Cho, Sung-Hwan Park, Seung-Ki Kwok
OBJECTIVES: Ethyl pyruvate (EP) is the ethyl ester of pyruvate and has antioxidative and anti-inflammatory effects. This study aimed to evaluate the therapeutic effect of EP in inflammatory arthritis and to identify the underlying mechanisms. METHODS: Mice with collagen-induced arthritis (CIA) were treated with the vehicle control or EP at 20mg/kg, and clinical and histological analyses were performed on the animals. The differentiation of murine CD4+ T cells into T helper 17 (Th17) cells in the presence of EP was investigated in vitro...
October 5, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28987811/the-interferon-gene-signature-is-increased-in-early-treatment-na%C3%A3-ve-rheumatoid-arthritis-and-predicts-a-poorer-response-to-initial-therapy
#5
Faye Ah Cooles, Amy E Anderson, Dennis W Lendrem, Julie Norris, Arthur G Pratt, Catharien Hilkens, John D Isaacs
The interferon gene signature in early, disease modifying drug naïve rheumatoid arthritis predicts clinical outcomes at 6 months after therapy initiation. We suggest type 1 interferons may be a future therapeutic target in early RA.
October 5, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28973003/salt-inducible-kinases-sik-inhibition-reduces-rankl-induced-osteoclastogenesis
#6
Maria Stella Lombardi, Corine Gilliéron, Majoska Berkelaar, Cem Gabay
Osteoclasts are large multinucleated cells responsible for bone resorption. Excessive inflammatory activation of osteoclasts leads to bony erosions, which are the hallmark of several diseases such as rheumatoid arthritis (RA). Salt-inducible kinases (SIK) constitute a subfamily of kinases comprising three members (SIK1, -2, and -3). Inhibition of SIK kinase activity induces an anti-inflammatory phenotype in macrophages. Since osteoclasts originate from precursors of macrophage origin, we hypothesized a role of SIK in osteoclastogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28959261/a-novel-approach-to-reinstating-tolerance-in-experimental-autoimmune-myasthenia-gravis-using-a-targeted-fusion-protein-mcta1-t146
#7
Alessandra Consonni, Sapna Sharma, Karin Schön, Cristina Lebrero-Fernández, Elena Rinaldi, Nils Yngve Lycke, Fulvio Baggi
Reinstating tissue-specific tolerance has attracted much attention as a means to treat autoimmune diseases. However, despite promising results in rodent models of autoimmune diseases, no established tolerogenic therapy is clinically available yet. In the experimental autoimmune myasthenia gravis (EAMG) model several protocols have been reported that induce tolerance against the prime disease-associated antigen, the acetylcholine receptor (AChR) at the neuromuscular junction. Using the whole AChR, the extracellular part or peptides derived from the receptor, investigators have reported variable success with their treatments, though, usually relatively large amounts of antigen has been required...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28918656/diagnosing-kingella-kingae-infections-in-infants-and-young-children
#8
Pablo Yagupsky
Kingella kingae is currently recognized as the prime etiology of skeletal system infections in children aged 6-48 months. The organism is notoriously fastidious, its growth is inhibited by synovial fluid and bone exudates, and its presence in clinical specimens is commonly missed by traditional culture methods. Areas covered: The present review discusses the use of improved laboratory methods to detect the organism in normally sterile body fluids, exudates, and upper respiratory tract specimens. Expert commentary: While inoculation of joint and bone exudates into blood culture vials dilutes the concentration of detrimental factors and significantly improves the isolation of the organism, novel PCR-based assays have enhanced sensitivity, shortened the time-to-detection of K...
October 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28887914/curcumin-attenuates-the-scurfy-induced-immune-disorder-a-model-of-ipex-syndrome-with-inhibiting-th1-th2-th17-responses-in-mice
#9
Gihyun Lee, Hwan-Suck Chung, Kyeseok Lee, Hyeonhoon Lee, Minhwan Kim, Hyunsu Bae
BACKGROUND: Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) is a lethal autoimmune disease caused by mutations in the Foxp3 gene scurfin (scurfy). Immunosuppressive therapy for IPEX patients has been generally ineffective and has caused severe side effects, however curcumin has shown immune regulation properties for inflammatory diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel diseases without side effects. OBJECTIVE: The aim of this study was to investigate whether curcumin would attenuate symptoms of IPEX in mouse model and would prolong its survival period...
September 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28864934/gene-therapy-for-chondral-and-osteochondral-regeneration-is-the-future-now
#10
REVIEW
Daniele Bellavia, F Veronesi, V Carina, V Costa, L Raimondi, A De Luca, R Alessandro, M Fini, G Giavaresi
Gene therapy might represent a promising strategy for chondral and osteochondral defects repair by balancing the management of temporary joint mechanical incompetence with altered metabolic and inflammatory homeostasis. This review analysed preclinical and clinical studies on gene therapy for the repair of articular cartilage defects performed over the last 10 years, focussing on expression vectors (non-viral and viral), type of genes delivered and gene therapy procedures (direct or indirect). Plasmids (non-viral expression vectors) and adenovirus (viral vectors) were the most employed vectors in preclinical studies...
September 1, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28863153/triple-dmard-treatment-in-early-rheumatoid-arthritis-modulates-synovial-t-cell-activation-and-plasmablast-plasma-cell-differentiation-pathways
#11
Alice M Walsh, Mihir D Wechalekar, Yanxia Guo, Xuefeng Yin, Helen Weedon, Susanna M Proudman, Malcolm D Smith, Sunil Nagpal
OBJECTIVES: This study sought to investigate the genome-wide transcriptional effects of a combination of disease modifying anti-rheumatic drugs (tDMARD; methotrexate, sulfasalazine and hydroxychloroquine) in synovial tissues obtained from early rheumatoid arthritis (RA) patients. While combination DMARD strategies have been investigated for clinical efficacy, very little data exists on the potential molecular mechanism of action. We hypothesized that tDMARD would impact multiple biological pathways, but the specific pathways were unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28804691/combination-of-celecoxib-celebrex-%C3%A2-and-cd19-car-redirected-ctl-immunotherapy-for-the-treatment-of-b-cell-non-hodgkin-s-lymphomas
#12
REVIEW
Tam Nm Dinh, Alexandra S Onea, Ali R Jazirehi
The nonsteroidal anti-inflammatory drug (NSAID) Celecoxib (Celebrex(®)) received Food and Drug Administration (FDA) approval in 1998 for treatment of osteoarthritis and rheumatoid arthritis, and in recent years, its use has been extended to various types of malignancies, such as breast, colon, and urinary cancers. To maintain the survival of malignant B cells, non-Hodgkin's Lymphoma (NHL) is highly dependent on inflammatory microenvironment, and is inhibited by celecoxib. Celecoxib hinders tumor growth interacting with various apoptotic genes, such as cyclooxygenase-2 (Cox-2), B-cell lymphoma 2 (Bcl-2) family, phosphor-inositide-3 kinase/serine-threonine-specific protein kinase (PI3K/Akt), and inhibitors of apoptosis proteins (IAP) family...
2017: American Journal of Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28774272/identification-of-candidate-protective-variants-for-common-diseases-and-evaluation-of-their-protective-potential
#13
Joe M Butler, Neil Hall, Niro Narendran, Yit C Yang, Luminita Paraoan
BACKGROUND: Human polymorphisms with derived alleles that are protective against disease may provide powerful translational opportunities. Here we report a method to identify such candidate polymorphisms and apply it to common non-synonymous SNPs (nsSNPs) associated with common diseases. Our study also sought to establish which of the identified protective nsSNPs show evidence of positive selection, taking this as indirect evidence that the protective variant has a beneficial effect on phenotype...
August 3, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28747638/puma-gene-delivery-to-synoviocytes-reduces-inflammation-and-degeneration-of-arthritic-joints
#14
Saw-See Hong, Hubert Marotte, Guillaume Courbon, Gary S Firestein, Pierre Boulanger, Pierre Miossec
In rheumatoid arthritis (RA), the proliferation of fibroblast-like synoviocytes (FLS) is the cause of chronic inflammation in joints and of joint damage. Delivery of the pro-apoptotic gene PUMA to FLS via human adenovirus type 5 (HAdV5) vectors has been tested as a therapeutic approach, but efficiency is hampered by low transduction, as FLS do not express HAdV5 receptors on the cell surface. Here we show that efficient transduction of PUMA in FLS can be achieved by conjugating HAdV5 to a baculovirus, which binds to the cell surface via the envelope glycoprotein Gp64...
July 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28745729/highlights-of-skin-disease-education-foundation-s-41st-annual-hawaii-dermatology-seminar%C3%A2
#15
Kenneth B Gordon, Craig L Leonardi, Daniel E Furst, Neal Bhatia, Lawrence F Eichenfield, Katie Beleznay
New therapies, recent pathophysiological findings, and updated guidelines combined to create compelling presentations at the Skin Disease Education Foundation's 41st Annual Hawaii Dermatology Seminar™. This educational supplement summarizes the highlights of clinical sessions presented during this CME/CE conference. A growing understanding of the biology of psoriasis has facilitated the development of increasingly efficacious medications. Skin clearance used to be regarded as an impractical goal for psoriasis therapy...
June 2017: Seminars in Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28741989/mithramycin-has-inhibitory-effects-on-gliostatin-and-matrix-metalloproteinase-expression-induced-by-gliostatin-in-rheumatoid-fibroblast-like-synoviocytes
#16
Naoe Tatematsu, Yuko Waguri-Nagaya, Yohei Kawaguchi, Yusuke Oguri, Kenji Ikuta, Masaaki Kobayashi, Masahiro Nozaki, Kiyofumi Asai, Mineyoshi Aoyama, Takanobu Otsuka
OBJECTIVES: Gliostatin (GLS) has angiogenic and arthritogenic activities and enzymatic activity as thymidine phosphorylase. Aberrant GLS production has been observed in the synovial membranes of patients with rheumatoid arthritis (RA). Matrix metalloproteinases (MMPs) are involved in joint destruction. Promoters of GLS and some MMP genes contain Sp1 binding sites. We examined the inhibitory effect of the Sp1 inhibitor mithramycin on GLS-induced GLS and MMP expression in cultured fibroblast-like synoviocytes (FLSs)...
July 25, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28741869/increased-baseline-runx2-caspase-3-and-p21-gene-expressions-in-the-peripheral-blood-of-disease-modifying-anti-rheumatic-drug-na%C3%A3-ve-rheumatoid-arthritis-patients-are-associated-with-improved-clinical-response-to-methotrexate-therapy
#17
Elena V Tchetina, Natalia V Demidova, Galina A Markova, Elena A Taskina, Svetlana I Glukhova, Dmitry E Karateev
OBJECTIVE: To investigate the potential of the baseline gene expression in the whole blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis (RA) patients for predicting the response to methotrexate (MTX) treatment. METHODS: Twenty-six control subjects and 40 RA patients were examined. Clinical, immunological and radiographic parameters were assessed before and after 24 months of follow-up. The gene expressions in the whole blood were measured using real-time reverse transcription polymerase chain reaction...
July 25, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28736556/ras-signaling-inhibitors-attenuate-disease-in-adjuvant-induced-arthritis-via-targeting-pathogenic-antigen-specific-th17-type-cells
#18
Morad Zayoud, Victoria Marcu-Malina, Einav Vax, Jasmine Jacob-Hirsch, Galit Elad-Sfadia, Iris Barshack, Yoel Kloog, Itamar Goldstein
The Ras family of GTPases plays an important role in signaling nodes downstream to T cell receptor and CD28 activation, potentially lowering the threshold for T-cell receptor activation by autoantigens. Somatic mutation in NRAS or KRAS may cause a rare autoimmune disorder coupled with abnormal expansion of lymphocytes. T cells from rheumatoid arthritis (RA) patients show excessive activation of Ras/MEK/ERK pathway. The small molecule farnesylthiosalicylic acid (FTS) interferes with the interaction between Ras GTPases and their prenyl-binding chaperones to inhibit proper plasma membrane localization...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28728565/identification-of-differential-co-expressed-gene-networks-in-early-rheumatoid-arthritis-achieving-sustained-drug-free-remission-after-treatment-with-a-tocilizumab-based-or-methotrexate-based-strategy
#19
Xavier M Teitsma, Johannes W G Jacobs, Michal Mokry, Michelle E A Borm, Attila Pethö-Schramm, Jacob M van Laar, Johannes W J Bijlsma, Floris P J Lafeber
BACKGROUND: Methotrexate is endorsed to be used as first-line treatment in rheumatoid arthritis (RA). However, a large proportion of patients need additional treatment with a biological disease-modifying anti-rheumatic drug (DMARD) to adequately suppress their disease activity. A better understanding of genotypes could help to distinguish between patients with different pathogenic mechanisms. The aim of this study was therefore to identify networks of genes within DMARD-naive early RA patients associated with achieving sustained drug-free remission (sDFR) after initiating tocilizumab plus methotrexate, tocilizumab, or methotrexate therapy...
July 20, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28719732/genome-wide-association-meta-analysis-reveals-novel-juvenile-idiopathic-arthritis-susceptibility-loci
#20
Laura A McIntosh, Miranda C Marion, Marc Sudman, Mary E Comeau, Mara L Becker, John F Bohnsack, Tasha E Fingerlin, Thomas A Griffin, J Peter Haas, Daniel J Lovell, Lisa A Maier, Peter A Nigrovic, Sampath Prahalad, Marilynn Punaro, Carlos D Rosé, Carol A Wallace, Carol A Wise, Halima Moncrieffe, Timothy D Howard, Carl D Langefeld, Susan D Thompson
OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease and has a strong genomic component. To date, JIA genetic association studies have had limited sample sizes, used heterogeneous patient populations, or included only candidate regions. The aim of this study was to identify new associations between JIA patients with oligoarticular disease and those with IgM rheumatoid factor (RF)-negative polyarticular disease, which are clinically similar and the most prevalent JIA disease subtypes...
July 18, 2017: Arthritis & Rheumatology
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