Myasthenia gravis (MG) is an autoimmune disorder involving the neuromuscular junction that frequently affects the extra-ocular muscles (EOMs). It has been described as a very rare cause of bilateral EOM atrophy, but h...Myasthenia gravis (MG) is an autoimmune disorder involving the neuromuscular junction that frequently affects the extra-ocular muscles (EOMs). It has been described as a very rare cause of bilateral EOM atrophy, but histological analysis of such cases is lacking. A 66-year-old man presented with two months of right eyelid drooping and vertical diplopia. Examination showed bilateral ophthalmoparesis and complete right ptosis. The remainder of his exam was normal, and an MRI showed small EOMs. Acetylcholine receptor antibodies were elevated, establishing the diagnosis of MG. Oral corticosteroids and pyridostigmine followed by azathioprine improved his ptosis, but not his ophthalmoparesis. One year later he had surgical correction of his diplopia, and the resected superior rectus muscle showed complete replacement of EOM by connective tissue. MG can rarely cause bilateral EOM atrophy, which is characterized histologically by fibrosis in the muscle itself. Atrophy in the EOMs of a myasthenic patient may indicate a poor response to medical management alone.展开更多
In treating patients with obstetric brachial plexus palsy,we noticed that denervated intrinsic muscles of the hand become irreversibly atrophic at a faster than denervated biceps.In a rat model of obstetric brachial p...In treating patients with obstetric brachial plexus palsy,we noticed that denervated intrinsic muscles of the hand become irreversibly atrophic at a faster than denervated biceps.In a rat model of obstetric brachial plexus palsy,denervated intrinsic musculature of the forepaw entered the irreversible atrophy far earlier than denervated biceps.In this study,isobaric tags for relative and absolute quantitation were examined in the intrinsic musculature of forepaw and biceps on denervated and normal sides at 3 and 5 weeks to identify dysregulated proteins.Enrichment of pathways mapped by those proteins was analyzed by Kyoto Encyclopedia of Genes and Genomes analysis.At 3 weeks,119 dysregulated proteins in denervated intrinsic musculature of the forepaw were mapped to nine pathways for muscle regulation,while 67 dysregulated proteins were mapped to three such pathways at 5 weeks.At 3 weeks,27 upregulated proteins were mapped to five pathways involving inflammation and apoptosis,while two upregulated proteins were mapped to one such pathway at 5 weeks.At 3 and 5 weeks,53 proteins from pathways involving regrowth and differentiation were downregulated.At 3 weeks,64 dysregulated proteins in denervated biceps were mapped to five pathways involving muscle regulation,while,five dysregulated proteins were mapped to three such pathways at 5 weeks.One protein mapped to inflammation and apoptotic pathways was upregulated from one pathway at 3 weeks,while three proteins were downregulated from two other pathways at 5 weeks.Four proteins mapped to regrowth and differentiation pathways were upregulated from three pathways at 3 weeks,while two proteins were downregulated in another pathway at 5 weeks.These results implicated inflammation and apoptosis as critical factors aggravating atrophy of denervated intrinsic muscles of the hand during obstetric brachial plexus palsy.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Fudan University,China(approval No.DF-325)in January 2015.展开更多
基金supported by the Scientific Research Project from the Education Department of Liaoning Province,China(No.WZ2020001)the High-end Scientific Research Achievement Cultivation Project of Liaoning Normal University(No.203070142207).
文摘本研究通过对衰老大鼠进行运动训练,探究不同运动方式对神经肌肉接头(neuromuscular junction,NMJ)和骨骼肌相关蛋白代谢的影响及机制。从38只3月龄SPF级Sprague-Dawley(SD)雄性大鼠中随机选出10只作为青年对照组(Y组),其余养至21月龄后随机分为老年对照组(O组、8只)、耐力运动组(EN组、10只)、抗阻运动组(R组、10只)。经过相对应的8周训练后,取大鼠腓肠肌,用免疫荧光染色法检测S100B在施旺细胞上的表达水平。用Western blot检测凝集蛋白(Agrin)、低密度脂蛋白受体相关蛋白4(low-density lipoprotein receptor-related protein 4,Lrp4)、肌肉特异性激酶(muscle-specific kinase protein,MuSK)、酪氨酸激酶下游分子7(downstream of tyrosine kinase 7,Dok7)与磷酸化蛋白激酶B(phosphorylated protein kinase B,p-Akt)、磷酸化哺乳动物雷帕霉素靶蛋白(phosphorylated mammalian target of rapamycin,p-mTOR)、磷酸化叉头转录因子1(phosphorylated forkhead box O1,p-FoxO1)蛋白表达水平。结果显示,耐力和抗阻运动均提高衰老大鼠腓肠肌湿重比。R组S100B蛋白表达显著高于O组和EN组;与Y组比较,O组大鼠腓肠肌NMJ功能相关蛋白Agrin、Lrp4、MuSK、Dok7蛋白表达水平显著下调;衰老大鼠经过抗阻运动后,腓肠肌Agrin、Lrp4、MuSK、Dok7蛋白表达水平均显著上调,而衰老大鼠经耐力运动后仅Agrin蛋白表达水平显著上调,而Lrp4、MuSK、Dok7蛋白表达未得到改善。在骨骼肌相关蛋白代谢相关通路中,与Y组比较,O组大鼠腓肠肌p-Akt、p-mTOR蛋白表达水平下调,p-FoxO1蛋白表达水平上升;抗阻和耐力运动可逆转衰老大鼠p-mTOR和p-FoxO1蛋白表达的变化。以上结果表明,两种运动方式均可改善衰老大鼠NMJ功能,并增加骨骼肌蛋白质合成,降低骨骼肌蛋白质分解代谢,且抗阻运动效果更加显著。
文摘Myasthenia gravis (MG) is an autoimmune disorder involving the neuromuscular junction that frequently affects the extra-ocular muscles (EOMs). It has been described as a very rare cause of bilateral EOM atrophy, but histological analysis of such cases is lacking. A 66-year-old man presented with two months of right eyelid drooping and vertical diplopia. Examination showed bilateral ophthalmoparesis and complete right ptosis. The remainder of his exam was normal, and an MRI showed small EOMs. Acetylcholine receptor antibodies were elevated, establishing the diagnosis of MG. Oral corticosteroids and pyridostigmine followed by azathioprine improved his ptosis, but not his ophthalmoparesis. One year later he had surgical correction of his diplopia, and the resected superior rectus muscle showed complete replacement of EOM by connective tissue. MG can rarely cause bilateral EOM atrophy, which is characterized histologically by fibrosis in the muscle itself. Atrophy in the EOMs of a myasthenic patient may indicate a poor response to medical management alone.
基金supported by the National Natural Science Foundation of China,No.816019591003263(to JXW)the National Basic Research Program of China(973 Program),No.2014CB542203(to LC)
文摘In treating patients with obstetric brachial plexus palsy,we noticed that denervated intrinsic muscles of the hand become irreversibly atrophic at a faster than denervated biceps.In a rat model of obstetric brachial plexus palsy,denervated intrinsic musculature of the forepaw entered the irreversible atrophy far earlier than denervated biceps.In this study,isobaric tags for relative and absolute quantitation were examined in the intrinsic musculature of forepaw and biceps on denervated and normal sides at 3 and 5 weeks to identify dysregulated proteins.Enrichment of pathways mapped by those proteins was analyzed by Kyoto Encyclopedia of Genes and Genomes analysis.At 3 weeks,119 dysregulated proteins in denervated intrinsic musculature of the forepaw were mapped to nine pathways for muscle regulation,while 67 dysregulated proteins were mapped to three such pathways at 5 weeks.At 3 weeks,27 upregulated proteins were mapped to five pathways involving inflammation and apoptosis,while two upregulated proteins were mapped to one such pathway at 5 weeks.At 3 and 5 weeks,53 proteins from pathways involving regrowth and differentiation were downregulated.At 3 weeks,64 dysregulated proteins in denervated biceps were mapped to five pathways involving muscle regulation,while,five dysregulated proteins were mapped to three such pathways at 5 weeks.One protein mapped to inflammation and apoptotic pathways was upregulated from one pathway at 3 weeks,while three proteins were downregulated from two other pathways at 5 weeks.Four proteins mapped to regrowth and differentiation pathways were upregulated from three pathways at 3 weeks,while two proteins were downregulated in another pathway at 5 weeks.These results implicated inflammation and apoptosis as critical factors aggravating atrophy of denervated intrinsic muscles of the hand during obstetric brachial plexus palsy.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Fudan University,China(approval No.DF-325)in January 2015.
