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1.
Summary A necrotizing, nonprogressive myopathy with unusual paracrystalline inclusion bodies is described in a patient who underwent long-term treatment with megadoses of vitamin E. The clinical course and morphological findings suggest a close relationship to the administration of the vitamin. The theoretical pathogenesis of muscle damage and the possible origin of paracrystalline inclusion bodies are discussed.Presented at the Jahrestagung der österreichischen Gesellschaft für Neuropathologie in Bad Ischl, on April 17, 1986This study was supported by a grant from the Deutsche Forschungsgemeinschaft (Ba 916)  相似文献   
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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   
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Summary In ten patients with inclusion body myositis (IBM) five muscular biopsies showed profuse inflammatory exudates and three showed a few scattered inflammatory cells with partial invasion in some muscle fibers. No inflammatory cells were seen in two cases. In all patients, histopathological, histomorphometric and immunocytochemical studies were performed. Immunocytochemistry for the class I and class II major histocompatibility complex gene product (MHC) was performed in all cases and in ten control muscles including: normal muscles [3], dermatomyositis [3], polymyositis [3], scleroderma [1]. In the five cases of IBM with inflammatory exudates, subsets of lymphocytes were analyzed with a panel of monoclonal antibodies against B cells, T4 cells, T8 cells, K and natural killer cells and macrophages. Some muscle fibers expressed class I MHC antigens in the inflammatory cases of IBM. These fibers were near the inflammatory exudates and occasionally showed a partial invasion. No expression of class I MHC was found in normal muscles and in non-inflammatory cases of IBM. The antigen which triggers the mononuclear cells in the inflammatory forms of IBM is probably not the filamentous inclusions in rimmed vacuoles. In other inflammatory myopathies, expression of class I MHC was present on all fibers in polymyositis, only in the perifascicular area in dermatomyositis and in scleroderma. It could be suggested that the term inclusion body muscle disease be applied to cases with rimmed vacuoles and IBM-like filaments without inflammatory cells.  相似文献   
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林小燕  王文 《海峡药学》2009,21(10):18-20
目的摸索清火片的制备工艺,提高清火片的质量。方法以一步制粒法制备颗粒,并将薄荷脑用β-环糊精包合,制成包合物后加入压片。结果以该法制备的清火片,外观、成品颗粒、片剂崩解时限及包衣片的外观质量均优于传统制法。结论清火片工艺合理可行。  相似文献   
6.
目的 筛选制备大黄酚包合物的最佳工艺.方法 采用正交试验设计以包封率和栽药量为指标筛选最佳工艺条件,采用HPLC法测定其含量.结果 大黄酚与β-环糊精的比例为1:4,包合温度为40℃,包合时间为30 min,搅拌速度为200 r·min-1时包封率最高.结论 大黄酚包合物制备工艺简单、方便,体外释放速度快.  相似文献   
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制乳香、制没药挥发油β-环糊精包合工艺的研究   总被引:1,自引:0,他引:1  
目的:选择制乳香、制没药挥发油β-环糊精包合工艺的最佳工艺条件。方法:应用L9(34)正交试验法,以挥发油包合率、包合物得率为指标进行考察。结果:最佳工艺条件为β-环糊精、挥发油比例10∶1、包合温度50℃、包合时间120 m in。结论:该工艺条件适用于制乳香、制没药挥发油的包合。  相似文献   
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目的探讨大肠杆菌表达的卵巢癌抗独特型单链抗体/小鼠热休克蛋白70(6811ScFv/mHSP70)融合蛋白包涵体变性、复性条件,以确定其最佳体外复性条件。方法大肠杆菌表达大量融合蛋白6811ScFv/mHSP70:①比较不同的裂解液(8mol/L尿素和6mol/L盐酸胍)对包涵体的裂解效率及其对复性蛋白活性的影响;②探索序贯稀释方法,以及氧化还原环境和复性液中不同浓度L-精氨酸对蛋白稀释复性的影响;③比较稀释复性和柱。卜复性对融合蛋白复性效率及活性的影响。采用Bradford法测定包涵体裂解液与复性后蛋白浓度。所有复性蛋白活性的检测均采用ELISA方法。结果以包涵体形式表达6811ScFv/mHSP70蛋白:①经6mol/L盐酸胍裂解包涵体的效率远高于8mol/L尿素,但前者复性所得蛋白活性低,6mol/L盐酸胍彻底裂解的包涵体经8mol/L尿素透析后再复性,复性效率显著提高;②序贯稀释方法可提高蛋白复性效率;加入0.5mol/L L-精氨酸可降低稀释复性过程中蛋白聚集物的产生,提高复性效率;加入还原型谷胱甘肽(GSH)与氧化型谷胱甘肽(GSSH)浓度比为1:5时,可提高复性后蛋白活性;③柱上复性可一步完成蛋白的复性和纯化,所得蛋白纯度较高,但复性效率和复性后蛋白活性较稀释复性低。结论本研究建立了6811ScFv/mHSP70融合蛋白的最佳复性条件:包涵体经6mol/L盐酸胍彻底裂解后,再经8mol/L尿素透析,然后进行序贯稀释复性,且复性液中加入0.5mol/L L-精氨酸和GSH:GSSH=1:5以提高复性效率和蛋白活性,为进一步研究该蛋白的功能奠定了基础。  相似文献   
9.
A growing number of community childcare programs are including children with developmental disabilities. While some studies have explored the effects of inclusion for preschool and school‐age children without disabilities, there is little knowledge about inclusion for typically developing toddlers enrolled in such programs or about parent attitudes regarding inclusion. In this study, parent perceptions of the benefits and limitations of their child's toddler program (inclusion or typical) were assessed. Parents from both programs gave comparable responses to a semi‐structured survey with regard to changes in their child's development and parental level of satisfaction. Parent feedback from the inclusion childcare program also provided insight into the advantages of an inclusion program. These findings suggest that there is little differentiation between inclusion programs and regular childcare programs in providing a quality experience for all children, but that there may be additional benefits to enrolling children without disabilities into inclusion programs.  相似文献   
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