28 research outputs found
Anti-mitochondrial antibody: Potential marker of myositis with chronic clinical course, muscle atrophy, cardiac involvement and granulomatous inflammation in muscle biopsy
No full textAxisymmetric polydimethysiloxane microchannels for in vitro hemodynamic studies
No full textThe current microdevices used for biomedical research are often manufactured using microelectromechanical systems (MEMS) technology. Although it is possible to fabricate precise and reproducible rectangular microchannels using soft lithography techniques, this kind of geometry may not reflect the actual physiology of the microcirculation. Here, we present a simple method to fabricate circular polydimethysiloxane (PDMS) microchannels aiming to mimic an in vivo microvascular environment and suitable for state-of-the-art microscale flow visualization techniques, such as confocal µPIV/PTV. By using a confocal µPTV system individual red blood cells (RBCs) were successfully tracked trough a 75 µm circular PDMS microchannel. The results show that RBC lateral dispersion increases with the volume fraction of RBCs in the solution, i.e. with the hematocrit
Beetroot betalain inhibits peroxynitrite-mediated tyrosine nitration and DNA strand cleavage
No full textTwo major betalains, red-purple betacyanins and yellow betaxanthins, were isolated from red beetroots (Beta vulgaris L.), and their peroxynitrite (ONOO-) scavenging capacity was investigated. Apparent colours of the betalains were bleached by the addition of ONOO-, and the absorbance decreases were suppressed in the presence of glutathione, a ONOO- scavenger. After bleaching, a new absorption maximum was observed at 350 nm in the spectrum of the resulting reaction mixture. New peaks were detected from HPLC analysis of the reaction products of betanin, a representative constituent of red beetroot betacyanins, treated with ONOO- monitoring at 350 nm, and the intensity of the major peak was positively correlated with ONOO- concentration. Betanin inhibited the ONOO- (0.5 mM)-dependent nitration of tyrosine (0.1 mM). Additionally, the IC50 value of betanin (19.2 μM) was lower than that of ascorbate (79.6 μM). The presence of betanin (0.05-1.0 μM) also inhibited ONOO- (0.5 mM)-dependent DNA strand cleavage in a concentration-dependent manner. These results suggest that betalains can protect cells from nitrosative stress in addition to protecting them from oxidative stresses
Severe finger necrosis in antisynthetase syndrome with positive anti‐OJ antibodies
No full textKey Clinical Message In a patient with anti‐aminoacyl tRNA synthetase antibody and anti‐OJ antibody syndrome, interventions likes warming, prostaglandins, and antiplatelets failed. However, prednisolone pulse treatment rapidly halted disease progression. Patients with mild interstitial pneumonia, myositis, and extremity necrosis should be promptly considered for anti‐synthetase syndrome and receive immunosuppression after ruling out other causes. Abstract Anti‐aminoacyl tRNA synthetase (ARS) autoantibodies are myositis‐specific, and patients who test positive for ARS and have common clinical features are usually diagnosed with antisynthetase antibody syndrome (antisynthetase syndrome). Anti‐ARS antibodies include histidyl‐tRNA synthetase‐1 (Jo‐1), anti‐threonyl (PL‐7), anti‐alanyl (PL‐12), anti‐glycyl (EJ), anti‐asparaginyl (KS), anti‐tyrosyl (Ha), and anti‐phenylalanyl (Zo) tRNA synthetases. Among these, anti–isoleucyl tRNA synthetase (OJ) autoantibodies are extremely rare, and patients with these are frequently complicated by interstitial pneumonia. We report the case of an older man with ARS antibody syndrome who tested positive for anti‐OJ and anti‐Sjögren's‐syndrome‐related antigen A (Ro‐52) antibodies. He had muscle weakness due to myositis and unparalleled rapid and severe finger necrosis. Pulsed prednisolone effectively treated the myositis symptoms and terminated the progression of finger necrosis
Sporadic late‐onset nemaline myopathy as a rare cause of slowly progressive muscle weakness with young adult onset
No full textPhotocatalytic Reduction of Nitrobenzene to Aniline in an Aqueous Suspension of Titanium(IV) Oxide Particles in the Presence of Oxalic Acid as a Hole Scavenger and Promotive Effect of Dioxygen in the System
No full textNitrobenzene was effectively and selectively reduced to aniline in an acidic aqueous suspension of titanium(IV) oxide photocatalyst in the presence of oxalic acid as a hole scavenger and the aniline yield was improved in the presence of a small amount of dioxygen
Add-on effectiveness of methotrexate or iguratimod in patients with rheumatoid arthritis exhibiting an inadequate response to Janus kinase inhibitors: The ANSWER cohort study
No full textThis is a pre-copyedited, author-produced version of an article accepted for publication in Modern Rheumatology following peer review. The version of record, Ebina K., Hirano T., Maeda Y., et al. Add-on effectiveness of methotrexate or iguratimod in patients with rheumatoid arthritis exhibiting an inadequate response to Janus kinase inhibitors: The ANSWER cohort study. Modern Rheumatology 33, 690 (2023) is available online at: https://academic.oup.com/mr/article-abstract/33/4/690/6664276?redirectedFrom=fulltext and https://doi.org/10.1093/mr/roac092Objectives: This multicenter, retrospective study evaluated the effectiveness of add-on methotrexate (MTX) or iguratimod (IGU) in patients with rheumatoid arthritis exhibiting an inadequate response to Janus kinase inhibitors (JAKis). Methods: Forty-five patients were treated with new additional MTX (n = 22) or IGU (n = 23) and followed for 6 months. Patients' background is as follows: age, 59.2 years; disease activity score of 28 joints with C-reactive protein (DAS28-CRP), 3.4; clinical disease activity index, 15.7; biological disease-modifying antirheumatic drug (DMARD)-switched cases, 77.8%; first JAKi cases, 95.6%; and JAKi treatment: tofacitinib (n = 25), baricitinib (n = 17), upadacitinib (n = 2), and peficitinib (n = 1) for 9.6 months. Results: Thirty-five patients continued the combination therapy for 6 months without a significant change in concomitant glucocorticoid or other conventional synthetic DMARDs. DAS28-CRP (MTX, 3.6 to 2.6, p < 0.05; IGU, 3.3 to 2.1, p < 0.001) and clinical disease activity index (MTX, 16.7 to 8.8, p < 0.05; IGU, 14.6 to 6.5, p < 0.01) improved significantly from baseline. Using the 2019 European League Against Rheumatism criteria, 45.4% (MTX) and 39.1% (IGU) achieved moderate or good response and 40.9% (MTX) and 39.1% (IGU) achieved American College of Rheumatology 20% improvement criteria. Conclusions: Adding MTX or IGU to inadequate responders of JAKi can be considered as a complementary treatment
Clinicopathologic features of myositis patients with CD8-MHC-1 complex pathology
No full textObjective:To determine the clinical features of myositis patients with the histopathologic finding of CD8-positive T cells invading non-necrotic muscle fibers expressing major histocompatibility complex class 1 (CD8-MHC-1 complex), which is shared by polymyositis (PM) and inclusion body myositis (IBM), in relation to the p62 immunostaining pattern of muscle fibers.Methods:All 93 myositis patients with CD8-MHC-1 complex who were referred to our hospital from 1993 to 2015 were classified on the basis of the European Neuromuscular Center (ENMC) diagnostic criteria for IBM (Rose, 2013) or PM (Hoogendijk, 2004) and analyzed.Results:The 93 patients included were 17 patients with PM, 70 patients with IBM, and 6 patients who neither met the criteria for PM nor IBM in terms of muscle weakness distribution (unclassifiable group). For these PM, IBM, and unclassifiable patients, their mean ages at diagnosis were 63, 70, and 64 years; autoimmune disease was present in 7 (41%), 13 (19%), and 4 (67%); hepatitis C virus infection was detected in 0%, 13 (20%), and 2 (33%); and p62 was immunopositive in 0%, 66 (94%), and 2 (33%), respectively. Of the treated patients, 11 of 16 PM patients and 4 of 6 p62-immunonegative patients in the unclassifiable group showed responses to immunotherapy, whereas all 44 patients with IBM and 2 p62-immunopositive patients in the unclassifiable group were unresponsive to immunotherapy.Conclusions:CD8-MHC-1 complex is present in patients with PM, IBM, or unclassifiable group. The data may serve as an argument for a trial of immunosuppressive treatment in p62-immunonegative patients with unclassifiable myositis.</jats:sec
A systematic review of evidence on malignant spinal metastases : natural history and technologies for identifying patients at high risk of vertebral fracture and spinal cord compression
No full textBackground: Spinal metastases can lead to significant morbidity and reduction in quality of life due to spinal cord compression (SCC). Between 5% and 20% of patients with spinal metastases develop metastatic spinal cord compression during the course of their disease. An early study estimated average survival for patients with SCC to be between 3 and 7 months, with a 36% probability of survival to 12 months. An understanding of the natural history and early diagnosis of spinal metastases and prediction of collapse of the metastatic vertebrae are important.
Objective: To undertake a systematic review to examine the natural history of metastatic spinal lesions and to identify patients at high risk of vertebral fracture and SCC.
Data sources: The search strategy covered the concepts of metastasis, the spine and adults. Searches were undertaken from inception to June 2011 in 13 electronic databases [MEDLINE; MEDLINE In-Process & Other Non-Indexed Citations; EMBASE; Cochrane Database of Systematic Reviews; Cochrane Central Register of Controlled Trials (CENTRAL); Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database (NHS EED), HTA databases (NHS Centre for Reviews and Dissemination); Science Citation Index and Conference Proceedings (Web of Science); UK Clinical Research Network (UKCRN) Portfolio Database; Current Controlled Trials; ClinicalTrials.gov].
Review methods: Titles and abstracts of retrieved studies were assessed by two reviewers independently. Disagreement was resolved by consensus agreement. Full data were extracted independently by one reviewer. All included studies were reviewed by a second researcher with disagreements resolved by discussion. A quality assessment instrument was used to assess bias in six domains: study population, attrition, prognostic factor measurement, outcome measurement, confounding measurement and account, and analysis. Data were tabulated and discussed in a narrative review. Each tumour type was looked at separately.
Results: In all, 2425 potentially relevant articles were identified, of which 31 met the inclusion criteria. No study examined natural history alone. Seventeen studies reported retrospective data, 10 were prospective studies, and three were other study designs. There was one systematic review. There were no randomised controlled trials (RCTs). Approximately 5782 participants were included. Sample sizes ranged from 41 to 859. The age of participants ranged between 7 and 92 years. Types of cancers reported on were lung alone (n= 3), prostate alone (n= 6), breast alone (n= 7), mixed cancers (n= 13) and unclear (n= 1). A total of 93 prognostic factors were identified as potentially significant in predicting risk of SCC or collapse. Overall findings indicated that the more spinal metastases present and the longer a patient was at risk, the greater the reported likelihood of development of SCC and collapse. There was an increased risk of developing SCC if a cancer had already spread to the bones. In the prostate cancer studies, tumour grade, metastatic load and time on hormone therapy were associated with increased risk of SCC. In one study, risk of SCC before death was 24%, and 2.37 times greater with a Gleason score 7 than with a score of < 7 (p= 0.003). Other research found that patients with six or more bone lesions were at greater risk of SCC than those with fewer than six lesions [odds ratio (OR) 2.9, 95% confidence interval (CI) 1.012 to 8.35, p= 0.047]. For breast cancer patients who received a computerised tomography (CT) scan for suspected SCC, multiple logistic regression in one study identified four independent variables predictive of a positive test: bone metastases 2 years (OR 3.0 95% CI 1.2 to 7.6; p= 0.02); metastatic disease at initial diagnosis (OR 3.4, 95% CI 1.0 to 11.4; p= 0.05); objective weakness (OR 3.8, 95% CI 1.5 to 9.5; p= 0.005); and vertebral compression fracture on spine radiograph (OR 2.6, 95% CI 1.0 to 6.5; p= 0.05). A further study on mixed cancers, among patients who received surgery for SCC, reported that vertebral body compression fractures were associated with presurgery chemotherapy (OR 2.283, 95% CI 1.064 to 4.898; p= 0.03), cancer type [primary breast cancer (OR 4.179, 95% CI 1.457 to 11.983; p= 0.008)], thoracic involvement (OR 3.505, 95% CI 1.343 to 9.143; p= 0.01) and anterior cord compression (OR 3.213, 95% CI 1.416 to 7.293; p= 0.005).
Limitations: Many of the included studies provided limited information about patient populations and selection criteria and they varied in methodological quality, rigour and transparency. Several studies identified type of cancer (e.g. breast, lung or prostate cancer) as a significant factor in predicting SCC, but it remains difficult to determine the risk differential partly because of residual bias. Consideration of quantitative results from the studies does not easily allow generation of a coherent numerical summary, studies were heterogeneous especially with regard to population, results were not consistent between studies, and study results almost universally lacked corroboration from other independent studies.
Conclusion: No studies were found which examined natural history. Overall burden of metastatic disease, confirmed metastatic bone involvement and immediate symptomatology suggestive of spinal column involvement are already well known as factors for metastatic SCC, vertebral collapse or progression of vertebral collapse. Although we identified a large number of additional possible prognostic factors, those which currently offer the most potential are unclear. Current clinical consensus favours magnetic resonance imaging and CT imaging modalities for the investigation of SCC and vertebral fracture. Future research should concentrate on: (1) prospective randomised designs to establish clinical and quality-of-life outcomes and cost-effectiveness of identification and treatment of patients at high risk of vertebral collapse and SCC; (2) Service Delivery and Organisation research on magnetic resonance imaging (MRI) scans and scanning (in tandem with research studies on use of MRI to monitor progression) in order to understand best methods for maximising use of MRI scanners; and (3) investigation of prognostic algorithms to calculate probability of a specified event using high-quality prospective studies, involving defined populations, randomly selected and clearly identified samples, and with blinding of investigators
Chronic Myopathy Associated With Anti–Signal Recognition Particle Antibodies Can Be Misdiagnosed As Facioscapulohumeral Muscular Dystrophy
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