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81.

Background

Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious.

Objectives

Our aim was to deepen our understanding of the immune mechanisms involved in inclusion body myositis and identify specific biomarkers.

Methods

Using a panel of thirty-six markers and mass cytometry, we performed deep immune profiling of peripheral blood cells from inclusion body myositis patients and healthy donors, divided into two cohorts: test and validation cohorts. Potential biomarkers were compared to myositis controls (anti-Jo1-, anti-3-hydroxyl-3-methylglutaryl CoA reductase-, and anti-signal recognition particle-positive patients).

Results

Unsupervised analyses revealed substantial changes only within CD8+ cells. We observed an increase in the frequency of CD8+ cells that expressed high levels of T-bet, and containing mainly both effector and terminally differentiated memory cells. The senescent marker CD57 was overexpressed in CD8+T-bet+ cells of inclusion body myositis patients. As expected, senescent CD8+T-bet+ CD57+ cells of both patients and healthy donors were CD28nullCD27nullCD127null. Surprisingly, non-senescent CD8+T-bet+ CD57- cells in inclusion body myositis patients expressed lower levels of CD28, CD27, and CD127, and expressed higher levels of CD38 and HLA-DR compared to healthy donors. Using classification and regression trees alongside receiver operating characteristics curves, we identified and validated a frequency of CD8+T-bet+ cells >51.5% as a diagnostic biomarker specific to inclusion body myositis, compared to myositis control patients, with a sensitivity of 94.4%, a specificity of 88.5%, and an area under the curve of 0.97.

Conclusion

Using a panel of thirty-six markers by mass cytometry, we identify an activated cell population (CD8+T-bet+ CD57- CD28lowCD27lowCD127low CD38+ HLA-DR+) which could play a role in the physiopathology of inclusion body myositis, and identify CD8+T-bet+ cells as a predominant biomarker of this disease.  相似文献   
82.
股骨上端形态曲线的测量、参数化与统计分析   总被引:1,自引:1,他引:1  
通过对84根完好的中国人成人股骨标本进行正位和侧位两个方向的X线摄影,得到股骨正、侧两方位的X光片。对X光片上股骨上端髓腔内侧形态进行描绘,将描绘好的图像输入计算机,由计算机进行图像预处理后提取其曲线形态数据,并将形态数据参数化,从而得到可比较的、能准确表现股骨形态的量化数据,为股骨形态的分类分析和系列型人工髋关节的参数设计打下基础。  相似文献   
83.
Aqueous extracts of tree pollen were partially purified and polymerized with methods previously established for preparation of ragweed and grass polymers. The polymerized tree preparations were antigenic as demonstrated by ability to elicit immediate-type skin reactivity in humans and to induce an immune response in rabbits. The polymerized tree antigen was 100- to 10,000-fold less skin reactive than monomer tree antigen in tree pollen-sensitive patients but both preparations had similar antigenicity in rabbits. These results demonstrate that polymerized tree antigens can be prepared and should have the therapeutic potential already demonstrated for polymerized ragweed preparations.  相似文献   
84.
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is spreading at a rapid pace, and the World Health Organization declared it as pandemic on 11 March 2020. Mycoplasma pneumoniae is an "atypical" bacterial pathogen commonly known to cause respiratory illness in humans. The coinfection from SARS-CoV-2 and mycoplasma pneumonia is rarely reported in the literature to the best of our knowledge. We present a study in which 6 of 350 patients confirmed with COVID-19 were also diagnosed with M. pneumoniae infection. In this study, we described the clinical characteristics of patients with coinfection. Common symptoms at the onset of illness included fever (six [100%] patients); five (83.3%) patients had a cough, shortness of breath, and fatigue. The other symptoms were myalgia (66.6%), gastrointestinal symptoms (33.3%-50%), and altered mental status (16.7%). The laboratory parameters include lymphopenia, elevated erythrocyte sedimentation rate, C-reactive protein, lactate dehydrogenase, interleukin-6, serum ferritin, and D-dimer in all six (100%) patients. The chest X-ray at presentation showed bilateral infiltrates in all the patients (100%). We also described electrocardiogram findings, complications, and treatment during hospitalization in detail. One patient died during the hospital course.  相似文献   
85.
The standardization procedures for polymerized ragweed (PRW) must evaluate activity of PRW with assessments that differ from those used for standard unmodified extracts. This is because PRW allergens are different from conventional ragweed extracts in that they are much greater in average molecular weight and much lower in allergenicity for equivalent immunogenicity. We have evaluated seven samples of PRW for three parameters: allergenicity as determined by cutaneous end point titration, molecular weight distribution as determined by Sephadex G-200 chromatography, and availability of antigen E (AgE) determinants as measured by the ability of an extract to inhibit AgE binding to antibody by using a modification of the Farr technique. The skin test titers and molecular weight profiles provide information as to the safety of a PRW preparation and antigen-binding inhibitory activity gives information about allergenicity and immunogenicity. Appropriate limits may be set for each of these parameters to standardize PRW for clinical use.  相似文献   
86.
An automatic colour image segmentation and cell counting software system has been developed for immunocytochemical analysis of stained tissue samples. The system was designed to count the total number of positive and negative cells in tissue samples treated with cytokine DNA probes from pigs naturally parasitised with Taenia solium metacestodes, using in situ hybridisation. A reaction index was calculated as the ratio of the number of cells with a positive reaction to the total number of cells (positives plus negatives) for each of five different probes. The objectives of automatic counting were to improve the reproducibility of the analysis and reduce the processing time of large image batches. A fast KNN classifier was used for colour segmentation. Watershed segmentation combined with edge detection was used to isolate individual cells that were then automatically labelled, using the results of the corresponding colour segmented image. Validation was performed on 122 non-training digital images with a total of 1069 positive cells and 1459 negative cells, with the following results: a mean true positive rate of 90.2% for positive cells and a mean true positive rate of 85.4% for negative cells. The corresponding mean false positive rates were 9.6% and 6.6%. The mean reaction index error of the automatic analysis was 5.35%. The processing of each digital image took 10 s on a Pentium IV PC.  相似文献   
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This report describes a spectrum of respiratory symptoms in workers exposed to trimellitic anhydride (TMA), a biologically reactive chemical used in the plastics industry. Fourteen workers who had worked on a unit which synthesized TMA were evaluated by clinical and immunologic methods. Respiratory syndromes induced by TMA inhalation included asthma and rhinitis of the immediate type, late onset asthma with systemic symptoms, and airway irritation. TMA was shown to couple rapidly to human serum albumin, forming an immunoreactive hapten-protein complex. The workers' immunologic reactivity to this complex could be quantitated and correlated with the three respiratory syndromes. The asthma-rhinitis syndrome was mediated by IgE antibody specific for the TMA hapten. The syndrome of late onset asthma with systemic symptoms was accompanied by elevated levels of TMA-specific IgG antibody. Rheumatoid factor in high titer was found in one worker with IgE-mediated asthma and in two workers with asthma of late onset. Lymphocyte reactivity of TMA-HSA was demonstrated in three workers representative of the three clinical syndromes. Leukocyte histamine release was demonstrated to TMA-HSA in one worker with high levels of IgE antibody specific for TMA-HSA who had severe symptoms of acute rhinitis and asthma.  相似文献   
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