重肌灵抗重症肌无力的主要药理作用及作用机制的研究
摘要
重肌灵是河北以岭医药研究院临床长期用于治疗重症肌无力（Myasthenia gravis，MG）的有效中药复方，主要由黄芪、人参、鹿茸等组成，临床治疗上千例MG患者，取得比较好的疗效，具有温理奇阳，扶元振颓作用。重症肌无力（MG）是重点累及神经一肌肉接头处突触后膜上乙酰胆碱受体，主要由乙酰胆碱受体抗体介导的，T细胞依赖性、补体参与的自身免疫性疾病。实验性自身免疫性重症肌无力(Experimental Autoimmune myasthenia gravis，EAMG)被认为是研究MG的重要动物模型，目前公认的EAMG模型是用电鳐（Torpedo）或电鳗的电器官提取，纯化的N2-乙酰胆碱受体(Acetylcholine receptor,AchR)作为抗原免疫动物而成。本论文以Lewis大鼠建立EAMG模型，从与MG发病机理密切相关的N2AchR抗原特异性细胞免疫和体液免疫入手，将研究重点集中在MG发病机制中最重要的环节Th亚型细胞及Th亚型细胞分泌产生细胞因子IL-4、IFN-r；胸腺又是T细胞发育成熟的部位，而引起MG、EAMG的直接因素是体内产生抗N2AchR抗体。所以将胸腺—Th亚群—IL4、IFN-r—抗N2AchR抗体为轴心，运用3H-TdR掺入、ELISA、原位杂交检测及细胞凋亡检测技术，从整体、组织、细胞、分子水平深入研究重肌灵抗重症肌无力的作用机理。主要研究内容如下：
1．大鼠EAMG模型建立 从电鳐电器官中提取N2AchR粗提物，N2AchR粗提物和完全福氏佐剂等量混合，模型组大鼠尾根部，足垫部，背部皮下多点注射上述含N2AchR抗原液0.5ml/只，分别于实验的第1日、第14日、第30日共免疫3次。于未次免疫的19-21日，从临床症状、体重、肌力、运动能力及肌电、肌肉中N2AchR损失率及血中抗N2AchR抗体滴度来评价模型是否成功。结果表明，模型组大鼠上述指标与正常组、佐剂组相比，均有显著差异P<0.01，说明模型建立成功。用本方法建立的模型经济、成功率高，方法易于普及，在临床症状，病理表现等方面与人类MG相似，可用来免疫大量动物，进行MG发病机理及药效学研究。
2．重肌灵对EAMG大鼠主要药效学研究 用N2AchR粗提物加完全福氏佐剂方法免疫Lewis大鼠，制备EAMG大鼠模型。观察重肌灵预防给药对EAMG大鼠的影响。重肌灵大中剂量（6.56g/kg、3.28g/kg）可明显改善EAMG大鼠临床症状（P<0.01和P<0.05），对EAMG组大鼠体重有提高作用；对大鼠攀网研究显示重肌灵大中剂量组能显著提高EAMG大鼠肌力（P<0.05），表明重肌灵有提高EAMG大鼠肌力作用；采用旷场试验分析发现，重肌灵大中剂量组可显著提高EAMG大鼠跨格次数和理毛次数（P<0.01和P<0.05），表明重肌灵显著改善EAMG大鼠的运动能力；采用ELISA法发现重肌灵三个剂量组均可降低EAMG大鼠血清中抗N2AchR抗体含量（P<0.01和P<0.05），三组呈量效关系；重肌灵大中剂量还可缓解EAMG大鼠连续低频电刺激（5Hz，10Hz）后出现的大鼠腓肠肌收缩的衰减（P<0.01和P<0.05）；重肌灵三个剂量组对EAMG大鼠后肢肌肉突触后膜上N2AchR数目有显著升高作用，（P<0.01和P<0.05），其受体数目分别为正常组的78%，60%，48.7%（模型组为31%）。以上结果证明重肌灵对EAMG模型大鼠有明显防治效果。现代医学治疗该病以糖皮质激素为主，但副作用多；中医中药治疗该病虽时有报道，但尚未开发为中药新药。本实验为将重肌灵开发为临床治疗重症肌无力的中药新药提供了有力的依据，必将带来一定的社会效益和经济效益。
3．重肌灵和地塞米松对EAMG大鼠及正常小鼠免疫功能的影响
3.1对EAMG大鼠免疫功能的影响 重肌灵大中小剂量能显著增强ConA诱导的
EAMG大鼠淋巴结T细胞增殖（P<0.01和P<0.05）；而地塞米松则明显抑制其增殖（P<0.01）；重肌灵大中小剂量能显著抑制纯化的N2AchR特异性抗原诱导EAMG大鼠淋巴结T细胞增殖（P<0.01）及DTH反应（P<0.01）；地塞米松则呈现明显的抑制作用。
3.2重肌灵对正常小鼠免疫功能的影响 重肌灵大中剂量能显著增强ConA和LPS诱导的正常小鼠脾T和B淋巴细胞增殖（P<0.01或P<0.05）；重肌灵大中剂量对正常小鼠抗体形成细胞功能具有明显促进作用，对血凝抗体滴度也有明显的提高作用（P<0.01）。
以上结果证明重肌灵能明显抑制N2AchR特异性抗原诱导的EAMG大鼠细胞免疫和体液免疫反应，但对ConA诱导的细胞免疫反而有增强作用；对正常小鼠ConA、LPS诱导的细胞免疫、体液免疫及对SRBC诱导的体液免疫有增强作用，证明重肌灵抗EAMG的作用是不同于西药免疫抑制剂地塞米松作用。
4．重肌灵对EAMG大鼠免疫调节机制的研究 采用ELISA法检测与MG、EAMG发生发展密切相关的Th1型因子IFN-r，Th2型因子IL-4变化，发现重肌灵大中剂量可显著下调EAMG大鼠血中升高的IL-4，IFN-r水平；采用原位杂交法观察重肌灵对EAMG大鼠胸腺IL-4，IFN-rmRNA表达的影响发现，重肌灵大中剂量组能显著降低EAMG大鼠胸腺IL4，IFN-rmRNA表达，结合对血中IL-4，IFN-r水平影响，可推测重肌灵抗EAMG机制可能是通过降低机体IL-4，IFN-rmRNA表达，减少IL-4，IFN-r分泌，纠正Th1、Th2免疫功能紊乱，从而降低抗N2AchR抗体产生。
5．重肌灵对EAMG大鼠胸腺细胞凋亡的影响 MG、EAMG存在N2AchR特异性T细胞凋亡的减少，采用TUNEL法，从基因水平观察重肌灵对EAMG大鼠胸腺细胞凋
Zhong Jiling is an effective herbal prescription to treat Myasthenia gravis (MG) mainly consisting in Radix Astragali Seu Hedysari, Radix Ginseng and Hairy Antler etc.. Zhong Jiling has been used to treat more than thousands MG cases and got good result. MG is an autoimmune disease, which mainly involves the antibody of acetylcholine receptor, located on posterior membrane of synapse at the junction of nerve-muscle and is conducted by acetylcholine receptor and relys on T-cell and complements join it. This thesis, which establishing EAMG model in rats and focusing on thymus-Th subgroup-IL4, IFN-r-anti-N2AchR antibody and N2AchR etc., studied the functional mechanism of Zhong Jiling preventing from MG from different level such as whole, tissue, cell and molecule. The main study contents are as below:
1. Establishment of EAMG model in rats First, extracted rough N2AchR from crassinarke dormitory Takagi electric organ and mixed it with CFA in the same amount, and then immunized for 3 times by multiple injecting antigen liquid contained N2AchR 0.5 ml/rat on tails, feet and backs of rats. The valuation of EAMG model is from clinical symptoms, weight, muscular force, muscular motion ability, Electromusculagram, loss rate of N2AchR in muscle and N2AchR titre in blood serum. The results show that, comparing with normal group and CFA group, the above indexes in model group have significant differences (p<0.01), which is the EAMG model is established successfully.
2. Study on pharmacodynamics of Zhong Jiling in EAMG rats This is to observe the prevention effect of Zhong Jiling to EAMG rats. The results are as below: Zhong Jling in big and medium amount (6.56g/kg, 3.28g/kg) notably improved the clinical symptoms of EAMG rats (p<0.01 and p<0.05) and increased weights in EAMG group; the study of rat climbing-net shows that Zhong Jiling in big and medium amount can notably improve muscular force of EAMG rats (p<0.05); the results of the study on motion ability of rats were that Zhong Jiling in big and medium amount increased rat's climbing net numbers and combing hair numbers (p<0.01 and p<0.05), it shows that Zhong Jiling can remarkably improve motion function of EAMG; Zhong Jiling in big, medium and small amount all reduced the level of anti- N2AchR-antibody in blood serum of EAMG rats(p<0.01 and p<0.05); Zhong Jiling in big and medium amount raised the contraction decline of rat musculus gastrocnemius after stimulating sciatic nerves of EAMG rat; Zhong Jiling in big, medium and small amount all increased the N2AchR numbers on posterior membrane of synapse of posterior leg muscle of EAMG rats(p<0.01 and p<0.05) and the receptor numbers are respectively 78%, 60% and 48.7% of normal group( model group id 31%).
The above results show that Zhong Jiling has a significant function of EAMG prevention and treatment.
3. Effects on immune function of Zhong Jiling to EAMG rats and normal mice
3.1 Effects on immune function of Zhong Jiling to EAMG rats Zhong Jiling in big, medium and small amount obviously enhanced T-cell proliferation of lymphocyte of EAMG rats induced by ConA (p<0.01 and P<0.05), and dexamethasone (DXM) restrained its proliferation (p<0.01); Zhong Jiling in big, medium and small amount inhibited T-cell proliferation of lymphocyte of EAMG rats induced by specificity antigen of purified N2AchR (p<0.01) and DTH reaction (p<0.01), and DXM has the same above effects as zhong Jiling.
3.2 Effects on immune function of Zhong Jiling to normal mice Zhong iling in big and medium amount enhanced T-cell proliferation of spleen of normal mice induced by ConA (p<0.01); Zhong Jiling in medium and small amount improved cells which produce antibody and increased the antibody titre of blood coagulation (p<0.01).
The above results show that Zhong Jiling can significantly inhibit cellular immunoreaction and humoral immunoreaction of EAMG rat induced by specificity antigen of N2AchR, but zhong jiling enhances cellular immunoreaction induced by ConA and humoral immunoreaction induced by SRBC. This has proved t
1．大鼠EAMG模型建立 从电鳐电器官中提取N2AchR粗提物，N2AchR粗提物和完全福氏佐剂等量混合，模型组大鼠尾根部，足垫部，背部皮下多点注射上述含N2AchR抗原液0.5ml/只，分别于实验的第1日、第14日、第30日共免疫3次。于未次免疫的19-21日，从临床症状、体重、肌力、运动能力及肌电、肌肉中N2AchR损失率及血中抗N2AchR抗体滴度来评价模型是否成功。结果表明，模型组大鼠上述指标与正常组、佐剂组相比，均有显著差异P<0.01，说明模型建立成功。用本方法建立的模型经济、成功率高，方法易于普及，在临床症状，病理表现等方面与人类MG相似，可用来免疫大量动物，进行MG发病机理及药效学研究。
2．重肌灵对EAMG大鼠主要药效学研究 用N2AchR粗提物加完全福氏佐剂方法免疫Lewis大鼠，制备EAMG大鼠模型。观察重肌灵预防给药对EAMG大鼠的影响。重肌灵大中剂量（6.56g/kg、3.28g/kg）可明显改善EAMG大鼠临床症状（P<0.01和P<0.05），对EAMG组大鼠体重有提高作用；对大鼠攀网研究显示重肌灵大中剂量组能显著提高EAMG大鼠肌力（P<0.05），表明重肌灵有提高EAMG大鼠肌力作用；采用旷场试验分析发现，重肌灵大中剂量组可显著提高EAMG大鼠跨格次数和理毛次数（P<0.01和P<0.05），表明重肌灵显著改善EAMG大鼠的运动能力；采用ELISA法发现重肌灵三个剂量组均可降低EAMG大鼠血清中抗N2AchR抗体含量（P<0.01和P<0.05），三组呈量效关系；重肌灵大中剂量还可缓解EAMG大鼠连续低频电刺激（5Hz，10Hz）后出现的大鼠腓肠肌收缩的衰减（P<0.01和P<0.05）；重肌灵三个剂量组对EAMG大鼠后肢肌肉突触后膜上N2AchR数目有显著升高作用，（P<0.01和P<0.05），其受体数目分别为正常组的78%，60%，48.7%（模型组为31%）。以上结果证明重肌灵对EAMG模型大鼠有明显防治效果。现代医学治疗该病以糖皮质激素为主，但副作用多；中医中药治疗该病虽时有报道，但尚未开发为中药新药。本实验为将重肌灵开发为临床治疗重症肌无力的中药新药提供了有力的依据，必将带来一定的社会效益和经济效益。
3．重肌灵和地塞米松对EAMG大鼠及正常小鼠免疫功能的影响
3.1对EAMG大鼠免疫功能的影响 重肌灵大中小剂量能显著增强ConA诱导的
EAMG大鼠淋巴结T细胞增殖（P<0.01和P<0.05）；而地塞米松则明显抑制其增殖（P<0.01）；重肌灵大中小剂量能显著抑制纯化的N2AchR特异性抗原诱导EAMG大鼠淋巴结T细胞增殖（P<0.01）及DTH反应（P<0.01）；地塞米松则呈现明显的抑制作用。
3.2重肌灵对正常小鼠免疫功能的影响 重肌灵大中剂量能显著增强ConA和LPS诱导的正常小鼠脾T和B淋巴细胞增殖（P<0.01或P<0.05）；重肌灵大中剂量对正常小鼠抗体形成细胞功能具有明显促进作用，对血凝抗体滴度也有明显的提高作用（P<0.01）。
以上结果证明重肌灵能明显抑制N2AchR特异性抗原诱导的EAMG大鼠细胞免疫和体液免疫反应，但对ConA诱导的细胞免疫反而有增强作用；对正常小鼠ConA、LPS诱导的细胞免疫、体液免疫及对SRBC诱导的体液免疫有增强作用，证明重肌灵抗EAMG的作用是不同于西药免疫抑制剂地塞米松作用。
4．重肌灵对EAMG大鼠免疫调节机制的研究 采用ELISA法检测与MG、EAMG发生发展密切相关的Th1型因子IFN-r，Th2型因子IL-4变化，发现重肌灵大中剂量可显著下调EAMG大鼠血中升高的IL-4，IFN-r水平；采用原位杂交法观察重肌灵对EAMG大鼠胸腺IL-4，IFN-rmRNA表达的影响发现，重肌灵大中剂量组能显著降低EAMG大鼠胸腺IL4，IFN-rmRNA表达，结合对血中IL-4，IFN-r水平影响，可推测重肌灵抗EAMG机制可能是通过降低机体IL-4，IFN-rmRNA表达，减少IL-4，IFN-r分泌，纠正Th1、Th2免疫功能紊乱，从而降低抗N2AchR抗体产生。
5．重肌灵对EAMG大鼠胸腺细胞凋亡的影响 MG、EAMG存在N2AchR特异性T细胞凋亡的减少，采用TUNEL法，从基因水平观察重肌灵对EAMG大鼠胸腺细胞凋
Zhong Jiling is an effective herbal prescription to treat Myasthenia gravis (MG) mainly consisting in Radix Astragali Seu Hedysari, Radix Ginseng and Hairy Antler etc.. Zhong Jiling has been used to treat more than thousands MG cases and got good result. MG is an autoimmune disease, which mainly involves the antibody of acetylcholine receptor, located on posterior membrane of synapse at the junction of nerve-muscle and is conducted by acetylcholine receptor and relys on T-cell and complements join it. This thesis, which establishing EAMG model in rats and focusing on thymus-Th subgroup-IL4, IFN-r-anti-N2AchR antibody and N2AchR etc., studied the functional mechanism of Zhong Jiling preventing from MG from different level such as whole, tissue, cell and molecule. The main study contents are as below:
1. Establishment of EAMG model in rats First, extracted rough N2AchR from crassinarke dormitory Takagi electric organ and mixed it with CFA in the same amount, and then immunized for 3 times by multiple injecting antigen liquid contained N2AchR 0.5 ml/rat on tails, feet and backs of rats. The valuation of EAMG model is from clinical symptoms, weight, muscular force, muscular motion ability, Electromusculagram, loss rate of N2AchR in muscle and N2AchR titre in blood serum. The results show that, comparing with normal group and CFA group, the above indexes in model group have significant differences (p<0.01), which is the EAMG model is established successfully.
2. Study on pharmacodynamics of Zhong Jiling in EAMG rats This is to observe the prevention effect of Zhong Jiling to EAMG rats. The results are as below: Zhong Jling in big and medium amount (6.56g/kg, 3.28g/kg) notably improved the clinical symptoms of EAMG rats (p<0.01 and p<0.05) and increased weights in EAMG group; the study of rat climbing-net shows that Zhong Jiling in big and medium amount can notably improve muscular force of EAMG rats (p<0.05); the results of the study on motion ability of rats were that Zhong Jiling in big and medium amount increased rat's climbing net numbers and combing hair numbers (p<0.01 and p<0.05), it shows that Zhong Jiling can remarkably improve motion function of EAMG; Zhong Jiling in big, medium and small amount all reduced the level of anti- N2AchR-antibody in blood serum of EAMG rats(p<0.01 and p<0.05); Zhong Jiling in big and medium amount raised the contraction decline of rat musculus gastrocnemius after stimulating sciatic nerves of EAMG rat; Zhong Jiling in big, medium and small amount all increased the N2AchR numbers on posterior membrane of synapse of posterior leg muscle of EAMG rats(p<0.01 and p<0.05) and the receptor numbers are respectively 78%, 60% and 48.7% of normal group( model group id 31%).
The above results show that Zhong Jiling has a significant function of EAMG prevention and treatment.
3. Effects on immune function of Zhong Jiling to EAMG rats and normal mice
3.1 Effects on immune function of Zhong Jiling to EAMG rats Zhong Jiling in big, medium and small amount obviously enhanced T-cell proliferation of lymphocyte of EAMG rats induced by ConA (p<0.01 and P<0.05), and dexamethasone (DXM) restrained its proliferation (p<0.01); Zhong Jiling in big, medium and small amount inhibited T-cell proliferation of lymphocyte of EAMG rats induced by specificity antigen of purified N2AchR (p<0.01) and DTH reaction (p<0.01), and DXM has the same above effects as zhong Jiling.
3.2 Effects on immune function of Zhong Jiling to normal mice Zhong iling in big and medium amount enhanced T-cell proliferation of spleen of normal mice induced by ConA (p<0.01); Zhong Jiling in medium and small amount improved cells which produce antibody and increased the antibody titre of blood coagulation (p<0.01).
The above results show that Zhong Jiling can significantly inhibit cellular immunoreaction and humoral immunoreaction of EAMG rat induced by specificity antigen of N2AchR, but zhong jiling enhances cellular immunoreaction induced by ConA and humoral immunoreaction induced by SRBC. This has proved t
引文
[1]Marengo TS, Harrison R,Lunt GG,et al. Rat or human acetylcholine receptor antigen for investgation of myasthenia gravis? Lancet 1979;24:1(8113):442.
[2]Drachmn DB. Myathenia gravis.N Eng J Med,1994 330(25):1797~1810.
[3]Lindstrom JM,Seybold ME,Lennon VA, et al.Antibody to acetylcholine receptor in myasthenia gravis.Neurology,1976;26(11):1054-9.
[4]Heaton RW,Arnold IR,Howard N,et al.Successful treatment of chylothorax and superior vena cava obstruction by radiothorapy.J Clin Immunol,1987;42(2)153-2.
[5]Engel AG,Fukuoka T,Lang B, et al. Lambert-Eaton myasthenic syndron IgG:early morphologic effects and immunolocalization at the motor endplate.Ann N Y Acad Sci,1987;505:333-45.
[6]Denmy F, John MA,Lewis DB, et al. Nosocomial Klebsiella pneumoniae colonization in a neonatal special care unit. Ann Trop Paediatr;1986;6(2):123-8.
[7]Elderfraw ME,et al.Molecular and functional properties of the acetylcholine-receptor Ann N Y Acad Sci ,1975;264:183.
[8]Lindstrom JM,et al:Experimental autoimmune myasthenia gravis:Biochemical andimmunochemical aspects.Ann N Y Acad Sci 1976,274:254.
[9]涂来慧，等.从电鳐发电器官提纯烟碱型乙酰胆碱受体制作兔实验性重症肌无力模型，中华神经精神科杂志 1981,14(1):16.
[10]陈丽筠，沈国光.黑斑双鳍电鳐（Narcine maculata）电器官Ach受体的分离、纯化及其某些特性研究 动物学杂志，1984,5(2):199.
[11]Arnold I Bruns J,Dahmen G,et al. Comparative study of the stabilizing effect of conservative functional measures of the unstable upper ankle joint. Unfall chirurgie .1987;13(6):320-5.
[12]Krolewshi J,Smereczynski A,Daniel B,et al.Intervertebral disks in the computerized tomographic picture of degenerative spondylolisthesis. Chir Narzadow Ruchu Ortop Pol.1987;52(6):447-51.
[13]Conti-Tronconi BM,Mclane KE,Raftery MA,et al. The nicotinic acetylcholine recepter :structure and autoimmune pathology. Crit Rev Biochem Mol Biol.1994;29(2):69-123.
[14]Christadoss P,Dauphines MJ,Immunotherapy for myastheniagravis:a murine model..J Immnuol,1986,136(7):2437-40.
[15]涂来慧，等 用双抗体免疫沉淀法检测重症肌无力患者血清中乙酰胆碱受体抗体，中华神经精神科杂志 1985，18（6）：330.
[16]Lindstrom J.Walter B, Einarson B,et al.Immunochemical similarities between subunits of acetylcholine receptor from Torpedo,Electrophorus,and mammalian muscle.Biochemistry 1979,18(21):4470-80.
[17]Gotti C,Mantegazza R,Clementi F, et al. New antigen for antibody detation in myasthenia gravis.Neurology,1984,34(3):374-7.
[18]肖保国，等 异种AchR检测抗AchR抗体的评价，上海免疫学杂志 1989，（9）2：99.
[19]Fukuoka T,Engel AG,Lang B,et al.Lambert-Eaton myasthenia Syndrome:Ⅱ.Immunoelectron microscopy localization of IgG at the mouse motor end-plate. Ann Neurol,1987;22(2):200-11.
[20]Newsom-Davis J,Willcox N,Schluep M, et al.Immunological heterogeneity and cellular mechanisms in myasthenia gravis. Ann N Y Acad Sci,1987,505:12-26.
[21]Takamori M. Progress in the field of neurology in the last 100years:Myasthenia gravis.Nippon Naika Gakkai Aasshi,2002;91(8):2354-61.
[22]宋东林，等 重症肌无力患者神经肌肉接头处的超微结构研究，中华神经科杂志，1998，31（5）：299.
[23]宋东林，等 实验性重症肌无力大鼠神经肌肉接头处的超微结构研究 中华神经科杂志，1994，27（3）：135.
[24]Swash M,Oxbury J,eds.Clinical neurology.vol2.London:Willim Clowes Limited,1991.1368-1394.
[25]Drachman DB. Myasthenia gravis. N Engl J Med ,1994;330(25):1797-810.
[26]Whiting PJ,Cooper J,Lindstrom JM.Antibodies in sera fyom patients with myasthenia gravis do not bind to nicotinic acetylcholine recepter from human brasin.J Neuroimmunol,1987,16:205.
[27]许贤豪 重症肌无力病人伴锥体束征，中华神经精神科杂志 1987，20：280.
[28]宿长军，游国雄，施有昆，等. 重症肌无力正中神经体感诱发电位研究 中国神经精神疾病杂志，1995，21：193.
[29]Weidenfeld J,Bodoff M,Saphier D,et al.Further studies of the stimulatory action of nicotine on adrenocortical function in the rat.Neeuroendocrinology,1989,50:132.
[30]李柱一 重症肌无力乙酰胆碱受体抗体对大鼠神经元烟碱型乙酰胆碱受体的作用 中华内科杂志 1997，36（1）：15.
[31]Wada E,Wada K,Boulter J,et al.Distyibution of alpha2,alpha3,alpha4 and beta2 neurol nicotinic recepter subunit mRNAs in the central nervous system:a hybridization histochemical study in the rat.J Comp Neurol,1989,284:314.
[32]Dominguez del Toro,Juiz JM,Pern X,et al.Immunocytochemical localization of the alpha 7 subunit of the nicotinic acetylcholine recepter in the rat central nervous system. J Comp Neurol,1994,349:325.
[33]Chini B,Raimond E,Elgoyhen AB,et al. Molecular cloning and chromosomal localization of the human alpha 7-nicotinic recepter subunit gene(CHRNA7). Genomiocs,1994,19:379.
[34]Fornasari D,ChiniB,Tarroni P,et al. Molecular choning of human neuronal nicotinic recepter alpha 3-subunit.Neurosci Lett,1990,111:351.
[35]Wang ZY,Qiao J,Link H,et al.Suppression of experimental autoimmune myasthenia gravis by oral administration of acetylcholine receptor.J. Neuroimmunol, 1993,44(2):209-14.Neuroimmunol,1993,44(2):209-14.
[36]Ma CG,Zhang GX,Xiao BG,et al.Cellular Mrna experission of interferon-gamma(IFN-GAMMA) in rats nasally tolerized against experimental autoimmune myasthenia gravis(MG). Clin Exp Immunol,1996,104(3):509-16.
[37Vincent A,Drachman DB. Myasthenia gravis.Adv neurol,2002;88:159-88.
[38]Tindall RS,Kent M,Wells L,et al. A rapid immunoadsorbent radioimmunoassay for anti-acetylcholine receptor antibody. J Immunol Methods,1981;45(1):1-14.
[39]Fulpius BW. Antiacetylcholine receptor antibodies and myasthenia gravis. Int Rev Neurobiol,1983;24:1-14.
[40]张振馨，邓发智，谭铭勋，等. 重症肌无力100例的临床分析. 中华神经精神科杂志，1984，179(4)：214-219.
[41]俞昌正，关新华，张新华，等. 免疫药物治疗重症肌无力症和免疫观察31例临床分析.中华神经精神科杂志，1981;14(1):19-22.
[42]许贤豪，等 中国免疫学杂志 ，1985，1：22.
[43]陈世铭，等 实验性重症肌无力症状与血清抗体水平的关系 上海免疫学杂志，1990，10（3）：137 。
[44]Engel AG,Sahashi K,Fumagalli G, et al. The immunopathology of acquired myasthenia gravis.Ann N Y Acad Sci,1981,377:158-74.
[45]Lindstrom J ,Tzartos S,Gullick W,et al. Structure and function of the zcetylcholine receptor molecule studied using monoclonal antibodies. Ann N Y Acad Sci, 1981,377:1-9.
[46]Mcintosh KR, linsley PS,Drachman DB. Effects on cellular and antibody responses of lymphocytes from rats with experimental autoimmune myasthenia gravis. Cell Immunol,1995;166(1):103-12.
[47]Soliven BC ,Lange DJ,Penn AS,et al. Seronegative myasthenia gravis Neurology, 1988;38(4):514-7.
[48]Kuks TB,Limburg,PC,Horst G,et al.Antibodies to skeletal muscle in myasthenia gravis.Part2.Prevalence in non-thymoma patients.J Neurol Sci,1993;120(1):78-81.
[49]Christadoss P,Lindstrom JM,Talal Net al. Immune response gene control of lymphocyte proliferation induced by acetylcholine receptor-specific helper factor derived from lmphocytes of myastheniac mice.J Immunol,1986;137(6):1845-9.
[50]Drachman DB. Myasthenia gravis. N Eng J Med,1994;330(25):1797-810.
[51]Oosterhuis HJ,Kuks JB,et al.Myasthenia gravis syndromes.Curr Opin Neurol Neurosurg,1992;5(5):638-44.
[52]No authors Listed. Myasthenia gravis:biology and treatment.Ann N Y Acad Sci,1987;505:1-94.
[53]Mossman S,Vincent A,Newsom-Davis J.Passive transfor of myasthenia gravis by immunoglobulins:lack of correlation between AchR with antibody bound,acetylcholine recepter loss and transmssion defect. J Neurol Sci,1988;84:15.
[54] Mossman S,Vincent A, Newsom-Davis J.Myasthenia gravis without acetylcholine recepter antibody:a distinct disease entity lancent,1986,1:116.
[55]Barret JR,Byrne Vincent A,et al. Plasma from patients with seronegative myasthenia gravis inhibit nAChR responses in the TE671 cell line .Pflugers-Arch,1994,428:492.
[56] 李柱一，等 抗体阴性重症肌无力患者血浆及其IgG和非IgG组分对AchR功能及α-BuTx结合实验的影响 中国神经免疫学和神经病学杂志，1997，4（3）：143.
[57]Sakmann B,Methfessel C,Mishina M,et al.Role of scetylcholine recepter subunits in gating of the channel. Nature,1988,318:538.
[58]Keesey J,Bein M,Mink J, et al.Detection of thymoma in myasthenia gravis.Neurology 1980;30(3):233-9.
[59]Penn AS,Schot Land and DL,et al.Antimuscle and antiacetylcholine receptor and antibodies in myasthenia gravis .Muscle Nerve 1986;9(5):407-15.
[60]Swash W,Ingram DA.Adverse effect of verapamil in myasthenia gravis. Muscle Nerve,1992;15(3):396-8.
[61]Ohta M,Ohta k,Itoh N,et al:Anti-skeletal muscle antibodies in the sera from myasthenia gravis with thymoma:indentification of anti-myosin,actomyosin,action,and α-actinin antibodies by asolid-phase radioimmunoassay and aWestern blotting analysis.Clinica Chimica Acta.1990;187:255.
[62]Mohan S,Barohn RJ,Krolick KA:Unexpected crossreacting between myosin and a main immunogenic region(MIR) of the Acetylcholine recepter by antisera obtained from myasthenia gravis patients.Clin.Immunol Immunopath.1994;70:266.
[63]]Mohan S,Barohn RJ,Jackson CE,et al:Evaluation of myosinreactive antibodies from apanel of myasthenia gravis patients.Clin. Immunol Immunopath.1994;70:266.
[64]Hans M,Warrick and James A spudich:Myosin structure and function in cell motility.Ann.Rev.Cell Biol.1987;3:379.
[65]Claudio T,Raftery MA.Inhibition of bungarotoxin binding to acetycholine receptors by antisera from animala with experimental autoimmune myasttthenia gravis J Suprramol Struc.1980;14:267.
[66]Pachner A R:Anti- acetycholine receptor antibodies block bungarotoxin binding to native human acetycholine receptor on the surface of TE671 cells.Neurology 1989;39:1057.
[67]Dan-Goor M and Muhlrad A:antibody directed against the 142-148 sequence of the myosin heavy chain interferes with myosin-actin interaction.Biochem.1991;30:400.
[68]Tong Swand Elzinga M:The squence of the NH2-terminal 204-residue fragment of the heavy chine sequence of rabbit skeletal muscle myosin.J.Biol.Chem.1983;258:13100.
[69]沈燕，仲人前，孔宪涛：自身抗体穿透活细胞膜的研究进展。国外医学免疫学分册 1998；21（1）32.
[70]Koren E,Koscec M,Wolfson-Reichlin M,et al:Murine and human antibodies to native DNA that cross-react with the A and D SnRNP polypeptides cause direct injury of cultured kidney cells.J.Immunology 1995;154(9):4857.
[71]De Lanerolle P,Srtass JD,Felsen R,et al:Effects of antibodies to myosin light chain kinase in contractility and myosin phosphorylation in chemically permeabilized smooth muscle .Circ.Res.1991;68:457.
[72]Barohn R.J.and Brey R. L.:Soluble terminal complement components in human myasthenia gravis.Clin Neurol Neurosurg,in Press,1993.
[73]Romi F,Gilhus NE,Varhaug JE,et al.Thymectomy in Nonthymoma Early-onset myasthenia gravis in correlation with Disease Severity and Muscle Autoantibodies.Eur Neurol,2003;49(4):210-7.
[74]Aarli J A, Gilhus NE ,Hofstad H,et al. CA-antibody:an immunological marher of thymic neoplasia in myasthenia gravis?Acta Neurol Scand 1987;76(1):55-7.
[75]张仁琴，涂来慧。应用ELISA法检测重症肌无力患者血清中胸腺瘤相关抗体。中国神经精神疾病杂志 1991：17（4）：210。
[76]涂来慧，张仁琴，黄德仁。用柠檬酸提取人类骨骼肌蛋白抗原检测胸腺瘤相关抗体的临床应用价值。第二军医大学学报，1992；13：547。
[77] Aarli J A.:Localization and properties of an acid-soluble muscle antigen reacting with antibodies in myasthenia gravis sera.Acta pathol.Microbiol.scand.1972;80:453.
[78]Gautel M,Lakey A,Barlo DP,et al.Titin antibodies in myasthenia gravis:indentification of amajor immunogenic region of titin.Neurology, 1993;43: 1581-1585.
[79]Voltz RD,Albrich WC,Nagele A,et al.Paraneoplastic myasthenia gravis:detection of anti-MGt30(titin) antibodies predicts thymic epiththelial tumor. Neurology, 1997;49:1454-1457.
[80]Aarli JA,Skeie GO,Myglland A,et al.Muscle striation antibodies in myasthenia gravis:diagnostic and functional significance.Ann N Y Acad Sci,1998,841:505-515.
[81]Kurzban G.P.,Wang K.Giant polypeptides of skeletal muscle titin:Sedimemtation equilibrium in guanidine hydrochloride.Biochem.Bio.Phys.Res.Commun.1988;150:1155.
[82]Furst D.O.,Osborn M.,Nave R.,et al.The organization of titin filaments in the half-sarcomere by monoclonal antibodies in immunoelectron microscopy:a map of ten nonreepetitive epitopes starting at the Z-line extends to the M-line.J.Cell.Biol.19988;106:1563.
[83]Mhiting A.,Wardale J.and Trinick J.:Does titin regulate the length of muscle thick filaments?J.Mol.Biol.1989;205:163.
[84]Magid A and Law D.J.:Myofibrils bear most of the resting tension in frog skeletal muscle .Science.1985;230:1280.
[85]Labeit S,Kolmerer B.Titins:giant proteins in charge of muscle ultrastructure and
elasticity.Science,1995;270:293-296.
[86]Aarli J.A.,Stefansson K.,Marton L.S.G.,et al:Patients with myasthenia gravis and thymomn have in their sera IgG autoantibodies against titin.Clin.Exp Immunol.1990;82:284.
[87]Drachman DB,Mcintosh KR,Yang B,et al.Factors that determine the severity of experimental myasthenia gravis.Ann N Y Acad Sci.1998;841:1262-82.
[88]Tindall.RSA.Humoral immunity in myasthenia gravis biochemical characterization of acquired anti-recepter antibodies snd clinical correlation.Ann Neurol 1981;10:437.
[89]乔健，等.重症肌无力病人血清中IgM型乙酰胆碱受体、突触前膜抗体检测及临床意义.临床神经病学杂志 1998；11（2）：87.
[90]Rash.JE,Albuqverque.EX,HudsonCS.Studies of human myasthenia gravis:dectorphysiological and ultrasstructural evidence compatible with antibody attachment to the acetylcholine recepter complex.Proc Natl Acad Sci.USSA 1976;73:4584.
[91]余贺.临床免疫技术.第一版.上海科学技术出版社，1982：10.
[92]王炜，吕传真，肖保国. 重症肌无力四种突触前后膜结合蛋白抗体的检测.中国神经精神疾病杂志，1996；22（3）：132-134.
[93]Breeze AL and dolly JO.Interactions between discrete neuronal membrane binding sites for the putative K+channel ligands beta-bungarotoxin and mast-cell-degranulating peptide.Eur J Biochem,1989;178:771.
[94]施玉梁.一个作用于突触前的神经肌肉阻断剂—川楝素.生理学报，1980;32:293.
[95]徐 科.众短尾蝮毒液分离的突触前毒素：β-蝮蛇毒液.科学通报，1990；1：1.
[96]Berrih S,Gaud C,Bach MA ,et al.Evaluation of T cell subsets in myasthenia gravis using anti-T cell monoclonal antibodies.Clin Exp Immunol 1981;45(1):1-8.
[97] Berrih S,More LE,Gaud C,et al.Anti-AchR antibodies,thymic histology and T cell subsets in myasthenia gravis.Neurology 1984;34(1):66-71.
[98]Haynes BF,Harden EA,Olanow CW, et al.Effect of thymectomy on peripheral lymphocyte subsets in myasthenia gravis.J Immunol 1983;131(2):773-7.
[99]Rajur,Navaneetham D,Protti MP,et al.TCR V usage by acetylcholine receptor -specific CD4+ T cell in myasthenia gravis.J Autoimmun,1997;10(2):203-17.
[100]Yuen MH,Protti MP,Diethelm-Okita B,et al.Immuno regulatory CD8+ cells recognize antigen-activated CD4+ cells in myasthenia gravis patients and in healthy controls.J Immunol. 1995:154(3):1508-20.
[101]Christadoss P, Dauphinee MJ.Immunotherapy for myasthenia gravis:a murine model.J Immunol,1986;136(7):2437-40.
[102]金伯泉，主编.细胞和分子免疫学.西安：世界图书出版公司，1994，269-286.
[103]黄煜敏，许贤豪，林嘉友，等.胸腺切除和激素治疗对重症肌无力患者淋巴细胞的影响.中华内科杂志，1995，34：514-517.
[104]韩 钊，等. 重症肌无力患者周围血中CD4+T淋巴细胞亚群的研究.中国神经免疫学和神经病学杂志，1999，6（2）：82-85.
[105]Morimoto C,Letvin JA,Boyd M,et al.The isolation and characterization of the human helper-inducer subsets.J Immunol,1985;134:3762-3769.
[106] Morimoto C,Letvin JA,Distaso WR,et al. The isolation and characterization of the human suppressor-inducer subsets.J Immunol,1985;134:1508-1515.
[107]Akbar ANL,Terry A,Timms PCL,et al.Loss of CD445RA and again of UCHL1 reactivity is a feature of primed T cells.J Immunol.1988,140:1271-1278.
[108]邱晓彦，综述.B-1细胞研究进展.国外医学免疫学分册，1996，19：235-239.
[109]Kawanami S,Kanaide A,Itoyama Y, et al.Lymphocute function in myasthrenia gravis.J Neurol Neurosurg Psychiatry 1979,42(8):734-40.
[110]Limburg PC,Hummel Tappel E,Oosterhuis HJ, et al.In vitro T-cell dependent B-cell activaty in myasthenia gravis.Clin Exp Immuinol.1985,61(1):31-8.
[111]Shinomiya N,yata J.B and T cell involvement in anti-acetylcholine receptor antibody fromation in myasthenia gravis.Clin Exp Immunol, 1981;46(2):277-85.
[112]Shinomiya N,Yata J,Sasazuki T.T-cell subsets regulating anti-zcetylcholine-receptor-antibody formation in myasthenia gravis and characterization of suppressor T-cell factors involved.Clin Immunol Immunopathol, 1984;33(2):182-90.
[113]Pachner AR,Kantor FS.IN vitro and in vivo actions of acetylcholine receptor educated suppressor T cell lines in murine experimental autoimmune myasthenia .Clin Exp Immunol, 1984;56(3):659-68.
[114]Lisak RP,Laramore L,Levinson AI.Suppressor T cells in myasthenia gravis and antibodies to acetylcholine receptor.Ann Neurol ,1986;19(1):87-9.
[115]Cox A,Lisak RP,Skolnik P.Effect of thymectomy on blood T-cell subsets in myasthenia gravis. Ann Neurol, 1986;19(3):297-8.
[116]Mosmann TR,Cheruinski H, Bond MW.Two types of murine helper T cell clone I.Definition according to profiles of lymphokine activities and secreted proteins.J Immunol, 1986;136(7):2348-47.
[117]Fernandez-Botran R,Sanders WM.Lymphokin-mediated regulation of the proliferative response of clones of T helper 1 and Thelper 2 cells.J Exp Med.1988;168(2):543-58.
[118]Mora A,Cortes C,Mateo EM,PlaM.Myasthenia gravis.Rev Esp Anestesio Reanim,1990;37(5):284-90.
[119]Drach DB.Targeting T cells in Myasthenia gravis.Ann Neurol,1999;46(4):553-5.
[120]Asano Y,Nakayama T,KuboM,et al.Analysis of two distinct B cell zctivation Pathways mediated by a monoclonal T helper cell.Ⅱ.T helper cell secretion of interleukin-4 selectively inhibits antigen-spesific B cell activation by cognate,but not noncognate. Interzctions with T cells.J Immunol 1988;140(2):419-26.
[121]DRACHMANDB.Myasthenia gravis[J].N Engl J Med,1994;330(25):1797-1810.
[122]SOMMER N,WILLCOX N,HARCOURT GC,et al. Myasthenia thymos and thymoma are selectively enriched in acetylcholine recepter reactive T cells[J].Ann Neurol,1990;28:312-319.
[123]叶师聪，吕传真. 重症肌无力的自身免疫性及其与胸腺的关系 上海医学，1988，11（6）：366-368.
[124]Oosterhuis HJGH:Myasthenia Gravis-Clinical neurology and neurosurgery monographs,Vol.5,P51,Churchill Livingstone,Edinburgh,1984.
[125]Berrih S ,Le Brigand H,Levasseur P,et al.Depletion of helper inducer T cell after thymectomy in myasthenia gravis. Clin Immunol Immunopathol, 1983;28(2):272-81.
[126]Ragheb S,Lisak RP.The thymus and myasthenia gravis.Chest Surg Clin N Am.,2001;11(2):311-27.
[127]Mingari MG,Melioli G,Moretta A,et al.Surface markers of cloned human T cells with helper or suppressor zctivity on pokeweed mitogen-driven B cell differention.Eur J Immunol 1982;12(10):900-3.
[128]Dalakas MG,Engel WK,Mcclure JE.Identification of human thymic epithelial cells with antibodies to thymosin alpha 1 in myasthenia gravis.A nn N Y Acad Sci , 1981;377:477-85.
[129]Emilie D,Devergne O,Cohen-kaminsky S.In situ production of interleukins in hyperplastic thymus from myasthenia gravis patients.Ann N Y Acad Sci,1993;681:100-2.
[130]Levinson AI,Wheatley LM.The thymus and the pathogenesis of myasthenia
gravis.Clin Immunol immunopathol,1996;78(1):1-5.
[131]Ragheb S,Lisak RP.The thymus and myasthenia gravis.Chest Surg Clin N Am,2001;11(2):311-27.
[132]Urschel JD,Grewal RP.Thymectomy for myasthenia gravis.Postgrad Med J,1998;74(869):139-44.
[133]Oosterhuis HJ,Kuks JB.Myasthenia gravis and myasthenic syndromes.Curr Opin Neurol Neurosurg,1992;5(5):638-44.
[134]Fujii Y,Monden Y,Hashimoto J, et al.Acetylcholine receptor antibody-producing cells in thymus and lymph nodes in myasthenia gravis.Clin Immunol Immunopathol,1985;34(1):141-6.
[135]Penn AS,Schotland DL,Lamme S, et al.Antimuscle and antiacetylcholine receptor antibodies in myasthenia gravis.Muscle Nerve,1986;9(5):407-15.
[136]Lisak RP,Levinson AI,Iweiman B, et al.In vitro synthesis of IgG and antibodies to AchR by peripheral and thymic lymphocytes.Ann N Y Acad Sci,1987;505:39-49.
[137]Aarli JA,Stefansson K,Marton LS,et,al. Patients eith myasthenia gravis and thymoma have in their sera IgG autoantibodies against titin.Clin Exp Immunol,1990;82(2):284-8.
[138]Hohlfeld R.Myasthenia gravis and thymoma:paraneoplastic failure of neuromuscular transmission.Lab Invest,1990;62(3):241-3.
[139]Wekerle H ,Kelelsen UP.Intrathymic pathogenesis and dual genetic control of myasthenia gravis.Lancet,1977;1(8013):678-80.
[140]薛启冥.重症肌无力与胸腺瘤.中华神经精神科杂志，1981;14(1):26-28.
[141]杜 英，等. 重症肌无力胸腺提取液及胸腺细胞免疫活性的研究.中国免疫学杂志，1997;13,116-118.
[142]韩佐宁，马树俊，龙振洲.胸腺细胞与胸腺基质相互作用.国外医学免疫学分册，1994；6：296.
[143]杜 英，等. 重症肌无力胸腺提取液蛋白分析及其与AchR-Ab关系的研究.上海免疫学杂志，2000；20（4）：225-226.
[144]吕 良，乔 健，吕传真. 重症肌无力患者血清非Ig成分对突触前、后膜受体及其相应抗体反应的影响.上海免疫学杂志，1998；18：81.
[145]Harito AA,Goodall GJ,Horecker BL.Prothymosinα:Isolation and properities of the major immunoreactive form of thymosinα1 in rat thymus.Proc Natl Acad Sci USA,1984;81:1008.
[146]殷 伟，乔 健，吕传真.重症肌无力实验模型中胸腺细胞凋亡及其机制的研究.上海免疫学杂志，2000；20（1）：44-46.
[147]Annger M,Wintersberger W,Steiner CW, et al.High levels of Bcl-2 protein in circulating T lymphocytes but not B lymphocytes of patients with systemic lupus eerythematosus.Arthr Rheum,1994;37:1423.
[148]Siegel RM,Katsumata M,Miyashita T,et al.An analysis of apoptosis in lymphoid organs and lupus disease in murine systemic lupus erythematosus.Clin Exp Immunol,1996;105:306.
[149]Onodera j,Nakamura,S,Nagano I,et al.Upregulation of Bcl-2 protein in the myasthenic thymus.Ann Neurol,1996;39:521.
[150]Gratiet-Dans J,Ding LY,Turka LA,et al.Bcl-2 proto-oncogene expression duing human T cell deelopment:evidence for biphasic regulation.J Immunol,1993;151:83.
[151]Veis DJ,Sentman CL,Bach EA,et al.Expression of the Bcl-2 protein in murine an human thymocytes and in peripheral T lyphocyte.J Immunol,1993;151:2546.
[152]Haury M,freitas A,Hermitte V,et al.The physiology of the Bcl-2 expression in murine B lymphocytes.Oncogene,1993;8:1257.
[153]Merino R,Ding L,Veis DJ,et al.Development regulation of the Bcl-2 protein and susceptibility to cell death in B lymphocytes.EMBO J,1994,13:683.
[154]岳 岚，宋作圭，柴莹等. 获得性自身免疫性重症肌无力患者胸腺组织Bcl-2和Fas表达水平的研究.浙江医学，1999；21（6）321-323.
[155]Shiono H,Fujii Y,Okumura M,et al.Failure to down-regulate Bcl-2 protein in thymic geminal center Bcells in mythasenia gravis.Eur Immunol,1997;27:805.
[156]Moulian N,Bidault J,Truffault F,et al.Thymocyte Fas exprssion is dysregulated in myasthenia gravis patients with anti-acetylcholine recepter antibody.Blood,1997;89:3287.
[157]Masunaga A,Arai T,Yoshitake T,et al.Reduced expression of apoptosis-related antigens in from patients with myasthenia gravis.Immunol Lett,1994;39:167.
[158]Heidenreich F,Vincent A.Antibodies to ion-channel proteins in thymoma with myasthenia neuromyotonia and peripheral neuropathy.Neurology,1998;50(5):1438-5.
[159]Zhang GX,Navikas V,Link H.Cytokines and the phathogenesis of myasthenia gravis.Muscle Nerve,1997;20:543-551.
[160]刘绪宏，等.大鼠重症肌无力中枢受损时白细胞介素-1的变化.中华内科杂志，1999；38（10）660-662.
[161]Powers GD,Miller RA.Heterogeneity among T helper cells.Interleukin-2 secretion and help for immunoglobulin secretion.J Immunol,1987;139(8):2567-72.
[162]Kern DE,Lachmann LB,Greenberg PD,et al.Lyt-2+ cells .Requirements for concanvacinA-induced proliferation and interleukin2 prodution.J Immunol,1987; 137(9):2880-7.
[163]Smith JB,Talal N.Significance of self-recognition and interleukin-2 for immunoregulation,autoimmunity and cancer.Scad J Immunol 1982;16(4):269-78.
[164]Chrisdodoss P，Dauphinee M,Lindstrom J, et al.Deficient T-cell mitogen response in murine experimental autoimmune myasthenia gravis :a defect in the adherent cell population.Cell Immunol,1983;79(2):358-66.
[165]章崇杰,吴慧君，徐文桢.重症肌无力患者周围血自然杀伤细胞活性的研究。中华神经精神科杂志,1987;20(5):269-271.
[166]李震中，杨明山，高波廷，等. 重症肌无力患者血清SIL-2R水平检测.中国神经免疫学和神经病学杂志，1997；4（1）：32-35.
[167]Cohen-Kaminsky S,Jacqes Y,Aime C,et al.Follow-up of soluble interluekin-2 recepter levels after thymectomy in patients with MG Clinical Immunology and Immunopathology,1992;62(2):190.
[168]耿新杰，王守亮，王炳旭. 重症肌无力患者血清sIL-2R的检测.中国免疫学杂志，1994；1：57.
[169]Confalonieri P,Antozzi C,Cornelio F,et al.Immune activation in myasthenia gravis:soluble interleukin-2 receptor,interferon-gamma and tumor necrosis factor-alpha levels in patients serum.J Neuroimmunol.1993;48(1):33-6.
[170]Wang ZY,Link H,Huang WX,et al.T cell immunity to acetylcholine receptor and its subunits in Lewis rats over the course of experimental autoimmune myasthenia gravis.Scand J Immunol,1993;37(5):615-22.
[171]Zhang GX,Ma CG,Xiao BG,et al.Suppression of experimental autoimmune myasthenia gravis after CD8 depletion is associated with decreased IFN-gamma and IL-4 .Scand J Immunol,1995;42(4):457-65.
[172]Ma CG,Zhang GX,Xiao BG,et al.Cellular mRNA experission of interferon-gamma(IFN-gamma),IL-4 and transforming growth factor-bata(TGF-beta) in rats.nasally to lerzed againat experimental autoimmune myasthenia gravis(EAMG).Clin Exp Immunol,1996;104(3):509-16.
[173]梁丽云，马存根，丰 玲.IFN-γ、IL-4、TGF-β在诱导EAMG耐受中的作用.免疫学杂志，2000，16（4）：275-277.
[173]国 红，等. 重症肌无力胸腺和外周血抗原特异性单个核细胞IFN-γ、IL-4的转录及表达.中国神经免疫学和神经病学杂志，1999；6（6）：67-72.
[174]孙 宏，国红，许贤豪，等. 重症肌无力患者外周血乙酰胆碱受体特异性T细胞sIL-2R、IFN-γ、IL-4的表达和转录.中华神经科杂志，1998；31（2）：79-82.
[175]Asthana D,Fujii Y,Huston GE,et al.Regulation of antibody prodution by helper T cell clones in experimental autoimmune myasthenia gravis is mediated by IL-4 and antigene-specific T cell factors.Clin Immunol Immunopathol,1993;67:240-248.
[176]Cohen-Kaminsky S,Devergne O,Delatre Related Articles,et al.Interleukin-6 Overproduction by cultured thymic epithelial cells from patients with myasthenia gravis is potentially in volved in thymic myperplasia.Eur Cytokin Netw,1993;4(2):121-32.
[177]王福生.白细胞介素-6（IL-6）研究进展.国外医学免疫学分册，1990；13：169.
[178]Shimada K,Koh CS,Yanagisawa N,et al.Detection of inteleukin-6 inserumand cerebyospinal fluid of patients with neuro-immunological disease.1993;42:934.
[179]李作孝，徐文桢，章崇杰，等. 重症肌无力患者外周血单个核细胞白细胞介素-6活性变化.中国神经精神疾病杂志，1997；23（1）：20-22.
[180]刘绪宏，等. 重症肌无力乙酰胆碱受体抗体致中枢损害时IL-6水平的研究.武警医学，2000；11（4）：195-198.
[181]Taqpin V,Toulmond S,Serrano A.Increase in IL-6、and TNF levels in rat brain following traumatic lesion Influence of pre- and post- traumatic treatment with Ro5 4864,a peripher1-type(p site)benzodiazepine lingand.J Neuroimmunol,1993;42(2):177-85.
[182]Toulmond S,Vigex,Fage D.Local infusion of interleukin-6 attenuates the neurotoxic effects of NMNA on rats striatal cholinergic neurons.
[183]Valerio A,Ferrario M,Dreano M.Soluble interleukin-6(IL-6) receptor /IL-6 fusion protein enhances in vitro differentitation of puyified rat oligodendnoglial lineage cells.Mol Cell Neurosci ,2002;21(4):602-15.
[184]Shi FD,Zhang GX,Bai XF,et al.Cellular Mrna expression of interferon-gamma(IFN-gamma) IL-4 and IL-10 relates toresistance to experimental autoimmune myasthenia gravis(EAMG) in goung Lewis rats.Clin Exp Immunol,1997;108(3):523-8.
[185]侯世芳，等. 重症肌无力患者外周血干扰素-γ和白细胞介素-10分泌性T检测.中华神经科杂志，2000，33（2）：107-109.
[186]Zhang gx,Xiao BG,Bakhiet M,et al.Both CD4+ and CD8+T cells are essential to induce experimental autoimmune myasthenia gravis.J Exp Med,1996;184:349-356.
[187]Ma CG,Zhang GX,Xiao BG,et al.Cellular Mrna expression of interferon-gamma(IFN-gamma) ,IL-4and transforming growth factor-beta(TGF-beta) in rats nasally tolerized against experimental autoimmune myasthenia gravis (EAMG).Clin Exp Immunol,1996;104(3):509-16.
[188]Boritz E,Palmer BE,Livingston B.Diverse repertoire of HIV-1 p24-specific,IFN-gamma-producing CD4+ T cell clones following immune reconstitution on highly active antire troviral therapy.2003;170(2):1106-16.
[189]Zhang GX,Navikas V,Link H,et al.Cytokins and the pathogenesis of myasthenia gravis. Muscle Nerve,1997;20(5):543-51.
[190]Spurkland A,Gilhus NE,Ronningen KS,et al.Myasthenia gravis patients with thymus hyperplasia and myasthenai gravis patients with thymoma display different
HLA associations. Tissue Antigens,1991;37(2):90-3.
[191]国 红，等.重症肌无力胸腺和外周血抗原特异性单个核细胞IFN-γ、IL-4的转录及表达.中国神经免疫学和神经病学杂志，1999；6（2）：67-72.
[192]孙 宏，等. 重症肌无力患者外周血乙酰胆碱受体特异性T细胞sIL-2R、IFN-γ、IL-4的表达和转录.中华神经科杂志，1998；31（2）：79-82.
[193]Link J.Interferon-γ,IL-4 and transform growth factor-βmRNA expression in multiple sclerosis and myasthenia gravis.Acta Neurol Scand.1994;158(supple):1-58.
[194]Moiola L,Karachunski P,Protti MP,et al.Epitopes on the beta subunit of human muscle acetylcholine recepter recognized by CD4+ cells of myasthenia gravis patients and healthy subunits.J Clin Invest,1994;93:1020-1028.
[195]Zhang GX,Ma CG,Xiao BG,et al.Autoreactive T cell responses and cytokin patterns reflect resistance to experimental autoimmune myasthenia gravis in Wistar Farth rats. Eur J Immunol,1996;26(11):2552-8.
[196]Balasa B,Deng C,Lee J,et al.Interferon-gamma is necessary for the genes of acetylcholine receptor induced clinical experimental autoimmune myastnenia gravis in mice. J Exp Med,1997;186(3):385-91.
[197]Shenoy M,Baron S,Wu B,et al.IFN-alpha trentment supresses the development of experimental autoimmune myasthenia gravis .J Immunol,1995;154(11):6203-8.
[198]Benigni F,Sado S,Pennica D.Cardiotrophin-1 inhibits tumor necrosis factor production in the heart and serum of lipopolysaccharide-treated mice and vitro in mouse blood cells.Am J Pathol,1996;149(6):1847-50.
[199]Nadif R,Tedicka A,Mintz M,et al. Effect of TNF and LAT polymorphisms on biological markers of response to oxidative stimuli in coal miners:a model of gene-environmemt interaction Tumor necrosis factor and lymphotoxin alpha.J Med Genet,2003;40(2):96-103.
[200]Ares MP,Stollenuerk M,Olsson A,et al. Decreased inducibility of TNF expression in lipidloaded macrophages.BMC Immunol,2002;3(1):13..
[201]Marriott JB,Clarke IA,Dredge K,et al.Thalidomide and its anslogues have distinct and opposing effects on TNF-alpha and TNFR2 during costimulation of both CD4+ and CD8+ T cells.Clin Exp Immunol,2002;130(1):75-84.
[202]Becker J C,Dummer K,Hartmann AA,et al. Shedding of ICAM-1 from human melanoma cell lines induced by IFN-gamma and tumor necrosis factor-alpha Functional consequences on cell-mediated cytotoxicity.J Immunol,1991;147(12):4398-401.
[203]Hill ME,Ferguson DJ,Austyn JM,et al.Potent immunostimalatory dendritic cells can be cultured in bulk from progrenitors in normal infantand adult myasthenic human thymus.Immunology,1999;97(2):325-32.
[204]李作孝，等. 重症肌无力患者血清TNF水平变化及其与AchRab产生的相关性研究.中华神经科杂志，1996；29（6）：354~356.
[205]Yotota S,Geppert TD,Lipsky PE.Enhacemeht of antigen-and mitogen-induced human T lmphocyte proliferration by tumor necrosis factor-α,J Immunol,1988,140:531.
[206]Rubin LA,Nelson DL.The soluble interleukin2 recepter:biology,function and clinical application.Ann Intern Med,1990;113:619.
[207]Becker J C,Kolanus w,Lonnemuann C,et al.Human natural clones enhance in vitro antibody production by tumor necrosis factor alpha and gama interferon.Scand J Immunol,1990;32:153.
[208]Kehrl J.Thevenin C,Rieckmann P,et al.Transforming growth factor beta suppresses human Blymphocyte Ig production by inhibiting Synthesis and the Swith from the
membrone form to the secreted form of Ig mRNA.J Immunol,1991;146:4016-4023.
[209]Wahl S M,Hunt D A,Wong HL,et al.Transforming growth factor beta is apotent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation.J Immunol,1992,149:3026-3032.
[210]Chantry D,Turner m,Abney E et al.Modulation of cytokine production by transforming growth factor-β.J Immunol,1989;142:4295-4300.
[211]Link J,Fredrikson S,Olsson T,et al.Orgon-specific autoantigens induce transforming growth factor-βmRNAexpression in mononuclear cells in multiple sclerosis and myasthenia gravis.Ann Neurol,1994;35:197-203.
[212]Wang ZY,Link H,Ljungdah A.Induction of interferon-gamma,interleukin-4,and transforming growth factor-beta in rats orally tolerized against experimental autoimmune myasthenia gravis.Cell Immunol,1994;157(2):353-68.
[213]Zhang GX,Ma CG,Xiao BG,et al.Suppression of experimental autoimmune myasthenia gravis after CD8 depletion is associated with decreased IFN-gamma and IL-4.Scand J Immunol,1995;42(4):457-65.
[214]He B,Link J,Navikas V,et al.Transforming growth factor beta1 suppresses auto-antigen induced expression of pro-inflammatory cytokines but not of interleukin-10 in multiple sclerosis and myasthenia gravis .J Neuroimmunol,1995;58:21-35.
[215]Shipman GF,Bloomfield CD,Smith KA,et al.The effect of slucocorticoid therapy on glucocorticoid recepters in leukemia and lymphoma.Blood,1981,58(6):1198.
[216]Gooduin TS,Messner RP,Williams R.Inhibitors of T cell mitogenesis:effect of mitogen dose.Cellular immunol,1979;45:303.
[217]Waage A,Bakke O.Glucocorticoids suppress the production of tumor necrosis factor by lipopolysaccharide-stimulated humanmonocytes.Immunology,1988;63(2):299-302.
[218]杨晓红，等.实验性重症肌无力小鼠脾淋巴细胞糖皮质激素受体测定.川北医学院学报，1998；13（2）：14-15.
[219]Pouplard A,Battazzo GF,doniach D et al.Binding of immunoglobulins to pituitary ACTH cells.Nature,1976;261:142.
[220]Besedorsky HO,Del Rey A,Sorkin B et al.Lymphoid cells produce an immunoregulatory glucocorticoid increasing factor(GIF) acting through the pituitary gland.Clin Exp Immunol,1985;59(3):6227.
[221]刘卫彬，等. 重症肌无力患者淋巴细胞糖皮质激素受体与激素疗效依赖性的关系.中国神经精神疾病杂志，1999；25（4）：195-197.
[222]Aoki T,Drachman DB,Asher DM, et al.Attempts to immplicate viruses in myasthenia gravis.Neurology,1985;35(2):185-92.
[223]Shirkey BL,Slavin S,Vistica BP,et al.Immunomodulatory effects of linomide in animals immunized with immunopathogenic retinal antigens:dissolciation between different immune functions.Clin Exo Immunol,1997;11108(3):539-44.
[224]Caponnet to G,Rossi E,Primavera A,et al.Mycophenolate nofetil:a new immunosuppressive approach.Eur Neurol,2001;46(1):53-4.
[225]Brenner T,Timore Y,Wirguin I,et al.IN vitro synthesis of antibodies to acetylcholine receptor by Epstein-Barr Virus-Stimulated B-lympholytes derived from patients with myasthenia gravis.J Neuroimmunol,1989;24(3):217-22.
[226]Nath A,Kerman RH,Novak IS,et al.Immune studies in human immunodeficiency virus. Neurology,1990;40(4):581-3.
[227]Stefansson K,Dieperink ME,Richman DP, et al.Sharing of epitopes by bacteria and nicotinic acetylcholine receptor:a possible role in the pathogenesis of myasthenia
gravis.Ann N Y Acad Sci,1987;505:451-60.
[228]Dwyer DS,Vakil M,Kearney JF, et al.Idiotypic network connectivity and a possible cause of myasthenia gravis.J Exp Med,1986;164(4):1310-8.
[229]Martin F,Corrigan FM,Donard OF,et al.Organotin compounds in trimethyltin-treated rats and in human brain in Alzheimers disease. Human Exp Toxicol,1997;16(9):512-5.
[230]Feltkamp Tew,et al.Myasthenia gravis auto-antibodies and HLA antigens.Br Med J,1974;1:131.
[231]Compston Das,et al.Clinical pathological HLA antigen and immunological evidence for disease heterogeneity on myasthenia gravis.Brain,1980;103:579.
[232]Naeim F et al.Association of HLA-B8,DRw3 and antiacetylcholine receptor antibodies in myasthenia gravis.Tissue Antigens,1978;12:381.
[233]Keesey J,et al.Acetylcholine receptor antibody titer and HLA-B8 antigen in myasthenia gravis.Arch Neurol,1982;39:73.
[234]Kaichi Kida,et al.Heterogeneity on Myasthenia gravis:HLA,phenotypes and autoantibody responses in ocular and generalized type.Annals of Neurology,1987;21:274.
[235]许贤豪.重症肌无力—120例实验和临床观察。中华神经科杂志，1985；6：321.
[236]徐文桢，等.重症肌无力患者HLA与抗乙酰胆碱受体抗体的研究.中华神经精神科杂志，1992；25（3）：150-153.
[237]Gigliotti D,Lefvent AK,Jeddi-Tehrani,et al.Over expression of select T cell receptor V gene families within CD4+ and CD8+ T cell subsets of myasthenia gravis patients.Mol Wed ,19962(4):452-9.
[238]Theofilopoulos A N.The basis of autoimmunity:Part 1 Mechanism of aberrant selfrecognition.Immunol Today,1995;16:90.
[239]Kronenberg M,Hood L E,et al.The molecular genetics of the T-cell antigen recepter and T-cell antigen recognition.Ann Rev Immunol,1986;4:529.
[240]Christadess P,Wu B,Shenoy M,et al.TCR gene usage in experimental autoimmune myasthenia gravis pathogensis.J Immunol,1995;154:3603.
[241]Berrih-Aknin S,Aime-Sempe c,Cohen-Kaminsky S,et al.In vivo preferential usag of TCR-Vβ8 in Torpedo acetylcholine receptor immune response in the murine experimental model of myasthenia gravis.J Neuroimmunol,1995;58:191.
[242]Hohlfeld R,Wekerle H.The thymus in myasthenia gravis.Neurol Clin North Am,1994;12:331.
[243Tesch H,Holhfeld R,,Toyka KV,et al.Analysis of immunoglobulin and T cell receptor gene rearrangements in the thymus of myasthenia gravis patients.J Neuroimmunol,1989;21:169.
[244]Kawada J,Ueda Y,Sakai K,et al.Rearrangement of T cell receptor gene in thymoma with myasthenia gravis.Muscle Nerve,1994,(Supple):S187.
[245]高 枫，李晓东，陈清棠，等. 重症肌无力T细胞受体基因重排的初步研究.中国神经免役学和神经病学杂志, 1997;4(2):74-76.
[2]Drachmn DB. Myathenia gravis.N Eng J Med,1994 330(25):1797~1810.
[3]Lindstrom JM,Seybold ME,Lennon VA, et al.Antibody to acetylcholine receptor in myasthenia gravis.Neurology,1976;26(11):1054-9.
[4]Heaton RW,Arnold IR,Howard N,et al.Successful treatment of chylothorax and superior vena cava obstruction by radiothorapy.J Clin Immunol,1987;42(2)153-2.
[5]Engel AG,Fukuoka T,Lang B, et al. Lambert-Eaton myasthenic syndron IgG:early morphologic effects and immunolocalization at the motor endplate.Ann N Y Acad Sci,1987;505:333-45.
[6]Denmy F, John MA,Lewis DB, et al. Nosocomial Klebsiella pneumoniae colonization in a neonatal special care unit. Ann Trop Paediatr;1986;6(2):123-8.
[7]Elderfraw ME,et al.Molecular and functional properties of the acetylcholine-receptor Ann N Y Acad Sci ,1975;264:183.
[8]Lindstrom JM,et al:Experimental autoimmune myasthenia gravis:Biochemical andimmunochemical aspects.Ann N Y Acad Sci 1976,274:254.
[9]涂来慧，等.从电鳐发电器官提纯烟碱型乙酰胆碱受体制作兔实验性重症肌无力模型，中华神经精神科杂志 1981,14(1):16.
[10]陈丽筠，沈国光.黑斑双鳍电鳐（Narcine maculata）电器官Ach受体的分离、纯化及其某些特性研究 动物学杂志，1984,5(2):199.
[11]Arnold I Bruns J,Dahmen G,et al. Comparative study of the stabilizing effect of conservative functional measures of the unstable upper ankle joint. Unfall chirurgie .1987;13(6):320-5.
[12]Krolewshi J,Smereczynski A,Daniel B,et al.Intervertebral disks in the computerized tomographic picture of degenerative spondylolisthesis. Chir Narzadow Ruchu Ortop Pol.1987;52(6):447-51.
[13]Conti-Tronconi BM,Mclane KE,Raftery MA,et al. The nicotinic acetylcholine recepter :structure and autoimmune pathology. Crit Rev Biochem Mol Biol.1994;29(2):69-123.
[14]Christadoss P,Dauphines MJ,Immunotherapy for myastheniagravis:a murine model..J Immnuol,1986,136(7):2437-40.
[15]涂来慧，等 用双抗体免疫沉淀法检测重症肌无力患者血清中乙酰胆碱受体抗体，中华神经精神科杂志 1985，18（6）：330.
[16]Lindstrom J.Walter B, Einarson B,et al.Immunochemical similarities between subunits of acetylcholine receptor from Torpedo,Electrophorus,and mammalian muscle.Biochemistry 1979,18(21):4470-80.
[17]Gotti C,Mantegazza R,Clementi F, et al. New antigen for antibody detation in myasthenia gravis.Neurology,1984,34(3):374-7.
[18]肖保国，等 异种AchR检测抗AchR抗体的评价，上海免疫学杂志 1989，（9）2：99.
[19]Fukuoka T,Engel AG,Lang B,et al.Lambert-Eaton myasthenia Syndrome:Ⅱ.Immunoelectron microscopy localization of IgG at the mouse motor end-plate. Ann Neurol,1987;22(2):200-11.
[20]Newsom-Davis J,Willcox N,Schluep M, et al.Immunological heterogeneity and cellular mechanisms in myasthenia gravis. Ann N Y Acad Sci,1987,505:12-26.
[21]Takamori M. Progress in the field of neurology in the last 100years:Myasthenia gravis.Nippon Naika Gakkai Aasshi,2002;91(8):2354-61.
[22]宋东林，等 重症肌无力患者神经肌肉接头处的超微结构研究，中华神经科杂志，1998，31（5）：299.
[23]宋东林，等 实验性重症肌无力大鼠神经肌肉接头处的超微结构研究 中华神经科杂志，1994，27（3）：135.
[24]Swash M,Oxbury J,eds.Clinical neurology.vol2.London:Willim Clowes Limited,1991.1368-1394.
[25]Drachman DB. Myasthenia gravis. N Engl J Med ,1994;330(25):1797-810.
[26]Whiting PJ,Cooper J,Lindstrom JM.Antibodies in sera fyom patients with myasthenia gravis do not bind to nicotinic acetylcholine recepter from human brasin.J Neuroimmunol,1987,16:205.
[27]许贤豪 重症肌无力病人伴锥体束征，中华神经精神科杂志 1987，20：280.
[28]宿长军，游国雄，施有昆，等. 重症肌无力正中神经体感诱发电位研究 中国神经精神疾病杂志，1995，21：193.
[29]Weidenfeld J,Bodoff M,Saphier D,et al.Further studies of the stimulatory action of nicotine on adrenocortical function in the rat.Neeuroendocrinology,1989,50:132.
[30]李柱一 重症肌无力乙酰胆碱受体抗体对大鼠神经元烟碱型乙酰胆碱受体的作用 中华内科杂志 1997，36（1）：15.
[31]Wada E,Wada K,Boulter J,et al.Distyibution of alpha2,alpha3,alpha4 and beta2 neurol nicotinic recepter subunit mRNAs in the central nervous system:a hybridization histochemical study in the rat.J Comp Neurol,1989,284:314.
[32]Dominguez del Toro,Juiz JM,Pern X,et al.Immunocytochemical localization of the alpha 7 subunit of the nicotinic acetylcholine recepter in the rat central nervous system. J Comp Neurol,1994,349:325.
[33]Chini B,Raimond E,Elgoyhen AB,et al. Molecular cloning and chromosomal localization of the human alpha 7-nicotinic recepter subunit gene(CHRNA7). Genomiocs,1994,19:379.
[34]Fornasari D,ChiniB,Tarroni P,et al. Molecular choning of human neuronal nicotinic recepter alpha 3-subunit.Neurosci Lett,1990,111:351.
[35]Wang ZY,Qiao J,Link H,et al.Suppression of experimental autoimmune myasthenia gravis by oral administration of acetylcholine receptor.J. Neuroimmunol, 1993,44(2):209-14.Neuroimmunol,1993,44(2):209-14.
[36]Ma CG,Zhang GX,Xiao BG,et al.Cellular Mrna experission of interferon-gamma(IFN-GAMMA) in rats nasally tolerized against experimental autoimmune myasthenia gravis(MG). Clin Exp Immunol,1996,104(3):509-16.
[37Vincent A,Drachman DB. Myasthenia gravis.Adv neurol,2002;88:159-88.
[38]Tindall RS,Kent M,Wells L,et al. A rapid immunoadsorbent radioimmunoassay for anti-acetylcholine receptor antibody. J Immunol Methods,1981;45(1):1-14.
[39]Fulpius BW. Antiacetylcholine receptor antibodies and myasthenia gravis. Int Rev Neurobiol,1983;24:1-14.
[40]张振馨，邓发智，谭铭勋，等. 重症肌无力100例的临床分析. 中华神经精神科杂志，1984，179(4)：214-219.
[41]俞昌正，关新华，张新华，等. 免疫药物治疗重症肌无力症和免疫观察31例临床分析.中华神经精神科杂志，1981;14(1):19-22.
[42]许贤豪，等 中国免疫学杂志 ，1985，1：22.
[43]陈世铭，等 实验性重症肌无力症状与血清抗体水平的关系 上海免疫学杂志，1990，10（3）：137 。
[44]Engel AG,Sahashi K,Fumagalli G, et al. The immunopathology of acquired myasthenia gravis.Ann N Y Acad Sci,1981,377:158-74.
[45]Lindstrom J ,Tzartos S,Gullick W,et al. Structure and function of the zcetylcholine receptor molecule studied using monoclonal antibodies. Ann N Y Acad Sci, 1981,377:1-9.
[46]Mcintosh KR, linsley PS,Drachman DB. Effects on cellular and antibody responses of lymphocytes from rats with experimental autoimmune myasthenia gravis. Cell Immunol,1995;166(1):103-12.
[47]Soliven BC ,Lange DJ,Penn AS,et al. Seronegative myasthenia gravis Neurology, 1988;38(4):514-7.
[48]Kuks TB,Limburg,PC,Horst G,et al.Antibodies to skeletal muscle in myasthenia gravis.Part2.Prevalence in non-thymoma patients.J Neurol Sci,1993;120(1):78-81.
[49]Christadoss P,Lindstrom JM,Talal Net al. Immune response gene control of lymphocyte proliferation induced by acetylcholine receptor-specific helper factor derived from lmphocytes of myastheniac mice.J Immunol,1986;137(6):1845-9.
[50]Drachman DB. Myasthenia gravis. N Eng J Med,1994;330(25):1797-810.
[51]Oosterhuis HJ,Kuks JB,et al.Myasthenia gravis syndromes.Curr Opin Neurol Neurosurg,1992;5(5):638-44.
[52]No authors Listed. Myasthenia gravis:biology and treatment.Ann N Y Acad Sci,1987;505:1-94.
[53]Mossman S,Vincent A,Newsom-Davis J.Passive transfor of myasthenia gravis by immunoglobulins:lack of correlation between AchR with antibody bound,acetylcholine recepter loss and transmssion defect. J Neurol Sci,1988;84:15.
[54] Mossman S,Vincent A, Newsom-Davis J.Myasthenia gravis without acetylcholine recepter antibody:a distinct disease entity lancent,1986,1:116.
[55]Barret JR,Byrne Vincent A,et al. Plasma from patients with seronegative myasthenia gravis inhibit nAChR responses in the TE671 cell line .Pflugers-Arch,1994,428:492.
[56] 李柱一，等 抗体阴性重症肌无力患者血浆及其IgG和非IgG组分对AchR功能及α-BuTx结合实验的影响 中国神经免疫学和神经病学杂志，1997，4（3）：143.
[57]Sakmann B,Methfessel C,Mishina M,et al.Role of scetylcholine recepter subunits in gating of the channel. Nature,1988,318:538.
[58]Keesey J,Bein M,Mink J, et al.Detection of thymoma in myasthenia gravis.Neurology 1980;30(3):233-9.
[59]Penn AS,Schot Land and DL,et al.Antimuscle and antiacetylcholine receptor and antibodies in myasthenia gravis .Muscle Nerve 1986;9(5):407-15.
[60]Swash W,Ingram DA.Adverse effect of verapamil in myasthenia gravis. Muscle Nerve,1992;15(3):396-8.
[61]Ohta M,Ohta k,Itoh N,et al:Anti-skeletal muscle antibodies in the sera from myasthenia gravis with thymoma:indentification of anti-myosin,actomyosin,action,and α-actinin antibodies by asolid-phase radioimmunoassay and aWestern blotting analysis.Clinica Chimica Acta.1990;187:255.
[62]Mohan S,Barohn RJ,Krolick KA:Unexpected crossreacting between myosin and a main immunogenic region(MIR) of the Acetylcholine recepter by antisera obtained from myasthenia gravis patients.Clin.Immunol Immunopath.1994;70:266.
[63]]Mohan S,Barohn RJ,Jackson CE,et al:Evaluation of myosinreactive antibodies from apanel of myasthenia gravis patients.Clin. Immunol Immunopath.1994;70:266.
[64]Hans M,Warrick and James A spudich:Myosin structure and function in cell motility.Ann.Rev.Cell Biol.1987;3:379.
[65]Claudio T,Raftery MA.Inhibition of bungarotoxin binding to acetycholine receptors by antisera from animala with experimental autoimmune myasttthenia gravis J Suprramol Struc.1980;14:267.
[66]Pachner A R:Anti- acetycholine receptor antibodies block bungarotoxin binding to native human acetycholine receptor on the surface of TE671 cells.Neurology 1989;39:1057.
[67]Dan-Goor M and Muhlrad A:antibody directed against the 142-148 sequence of the myosin heavy chain interferes with myosin-actin interaction.Biochem.1991;30:400.
[68]Tong Swand Elzinga M:The squence of the NH2-terminal 204-residue fragment of the heavy chine sequence of rabbit skeletal muscle myosin.J.Biol.Chem.1983;258:13100.
[69]沈燕，仲人前，孔宪涛：自身抗体穿透活细胞膜的研究进展。国外医学免疫学分册 1998；21（1）32.
[70]Koren E,Koscec M,Wolfson-Reichlin M,et al:Murine and human antibodies to native DNA that cross-react with the A and D SnRNP polypeptides cause direct injury of cultured kidney cells.J.Immunology 1995;154(9):4857.
[71]De Lanerolle P,Srtass JD,Felsen R,et al:Effects of antibodies to myosin light chain kinase in contractility and myosin phosphorylation in chemically permeabilized smooth muscle .Circ.Res.1991;68:457.
[72]Barohn R.J.and Brey R. L.:Soluble terminal complement components in human myasthenia gravis.Clin Neurol Neurosurg,in Press,1993.
[73]Romi F,Gilhus NE,Varhaug JE,et al.Thymectomy in Nonthymoma Early-onset myasthenia gravis in correlation with Disease Severity and Muscle Autoantibodies.Eur Neurol,2003;49(4):210-7.
[74]Aarli J A, Gilhus NE ,Hofstad H,et al. CA-antibody:an immunological marher of thymic neoplasia in myasthenia gravis?Acta Neurol Scand 1987;76(1):55-7.
[75]张仁琴，涂来慧。应用ELISA法检测重症肌无力患者血清中胸腺瘤相关抗体。中国神经精神疾病杂志 1991：17（4）：210。
[76]涂来慧，张仁琴，黄德仁。用柠檬酸提取人类骨骼肌蛋白抗原检测胸腺瘤相关抗体的临床应用价值。第二军医大学学报，1992；13：547。
[77] Aarli J A.:Localization and properties of an acid-soluble muscle antigen reacting with antibodies in myasthenia gravis sera.Acta pathol.Microbiol.scand.1972;80:453.
[78]Gautel M,Lakey A,Barlo DP,et al.Titin antibodies in myasthenia gravis:indentification of amajor immunogenic region of titin.Neurology, 1993;43: 1581-1585.
[79]Voltz RD,Albrich WC,Nagele A,et al.Paraneoplastic myasthenia gravis:detection of anti-MGt30(titin) antibodies predicts thymic epiththelial tumor. Neurology, 1997;49:1454-1457.
[80]Aarli JA,Skeie GO,Myglland A,et al.Muscle striation antibodies in myasthenia gravis:diagnostic and functional significance.Ann N Y Acad Sci,1998,841:505-515.
[81]Kurzban G.P.,Wang K.Giant polypeptides of skeletal muscle titin:Sedimemtation equilibrium in guanidine hydrochloride.Biochem.Bio.Phys.Res.Commun.1988;150:1155.
[82]Furst D.O.,Osborn M.,Nave R.,et al.The organization of titin filaments in the half-sarcomere by monoclonal antibodies in immunoelectron microscopy:a map of ten nonreepetitive epitopes starting at the Z-line extends to the M-line.J.Cell.Biol.19988;106:1563.
[83]Mhiting A.,Wardale J.and Trinick J.:Does titin regulate the length of muscle thick filaments?J.Mol.Biol.1989;205:163.
[84]Magid A and Law D.J.:Myofibrils bear most of the resting tension in frog skeletal muscle .Science.1985;230:1280.
[85]Labeit S,Kolmerer B.Titins:giant proteins in charge of muscle ultrastructure and
elasticity.Science,1995;270:293-296.
[86]Aarli J.A.,Stefansson K.,Marton L.S.G.,et al:Patients with myasthenia gravis and thymomn have in their sera IgG autoantibodies against titin.Clin.Exp Immunol.1990;82:284.
[87]Drachman DB,Mcintosh KR,Yang B,et al.Factors that determine the severity of experimental myasthenia gravis.Ann N Y Acad Sci.1998;841:1262-82.
[88]Tindall.RSA.Humoral immunity in myasthenia gravis biochemical characterization of acquired anti-recepter antibodies snd clinical correlation.Ann Neurol 1981;10:437.
[89]乔健，等.重症肌无力病人血清中IgM型乙酰胆碱受体、突触前膜抗体检测及临床意义.临床神经病学杂志 1998；11（2）：87.
[90]Rash.JE,Albuqverque.EX,HudsonCS.Studies of human myasthenia gravis:dectorphysiological and ultrasstructural evidence compatible with antibody attachment to the acetylcholine recepter complex.Proc Natl Acad Sci.USSA 1976;73:4584.
[91]余贺.临床免疫技术.第一版.上海科学技术出版社，1982：10.
[92]王炜，吕传真，肖保国. 重症肌无力四种突触前后膜结合蛋白抗体的检测.中国神经精神疾病杂志，1996；22（3）：132-134.
[93]Breeze AL and dolly JO.Interactions between discrete neuronal membrane binding sites for the putative K+channel ligands beta-bungarotoxin and mast-cell-degranulating peptide.Eur J Biochem,1989;178:771.
[94]施玉梁.一个作用于突触前的神经肌肉阻断剂—川楝素.生理学报，1980;32:293.
[95]徐 科.众短尾蝮毒液分离的突触前毒素：β-蝮蛇毒液.科学通报，1990；1：1.
[96]Berrih S,Gaud C,Bach MA ,et al.Evaluation of T cell subsets in myasthenia gravis using anti-T cell monoclonal antibodies.Clin Exp Immunol 1981;45(1):1-8.
[97] Berrih S,More LE,Gaud C,et al.Anti-AchR antibodies,thymic histology and T cell subsets in myasthenia gravis.Neurology 1984;34(1):66-71.
[98]Haynes BF,Harden EA,Olanow CW, et al.Effect of thymectomy on peripheral lymphocyte subsets in myasthenia gravis.J Immunol 1983;131(2):773-7.
[99]Rajur,Navaneetham D,Protti MP,et al.TCR V usage by acetylcholine receptor -specific CD4+ T cell in myasthenia gravis.J Autoimmun,1997;10(2):203-17.
[100]Yuen MH,Protti MP,Diethelm-Okita B,et al.Immuno regulatory CD8+ cells recognize antigen-activated CD4+ cells in myasthenia gravis patients and in healthy controls.J Immunol. 1995:154(3):1508-20.
[101]Christadoss P, Dauphinee MJ.Immunotherapy for myasthenia gravis:a murine model.J Immunol,1986;136(7):2437-40.
[102]金伯泉，主编.细胞和分子免疫学.西安：世界图书出版公司，1994，269-286.
[103]黄煜敏，许贤豪，林嘉友，等.胸腺切除和激素治疗对重症肌无力患者淋巴细胞的影响.中华内科杂志，1995，34：514-517.
[104]韩 钊，等. 重症肌无力患者周围血中CD4+T淋巴细胞亚群的研究.中国神经免疫学和神经病学杂志，1999，6（2）：82-85.
[105]Morimoto C,Letvin JA,Boyd M,et al.The isolation and characterization of the human helper-inducer subsets.J Immunol,1985;134:3762-3769.
[106] Morimoto C,Letvin JA,Distaso WR,et al. The isolation and characterization of the human suppressor-inducer subsets.J Immunol,1985;134:1508-1515.
[107]Akbar ANL,Terry A,Timms PCL,et al.Loss of CD445RA and again of UCHL1 reactivity is a feature of primed T cells.J Immunol.1988,140:1271-1278.
[108]邱晓彦，综述.B-1细胞研究进展.国外医学免疫学分册，1996，19：235-239.
[109]Kawanami S,Kanaide A,Itoyama Y, et al.Lymphocute function in myasthrenia gravis.J Neurol Neurosurg Psychiatry 1979,42(8):734-40.
[110]Limburg PC,Hummel Tappel E,Oosterhuis HJ, et al.In vitro T-cell dependent B-cell activaty in myasthenia gravis.Clin Exp Immuinol.1985,61(1):31-8.
[111]Shinomiya N,yata J.B and T cell involvement in anti-acetylcholine receptor antibody fromation in myasthenia gravis.Clin Exp Immunol, 1981;46(2):277-85.
[112]Shinomiya N,Yata J,Sasazuki T.T-cell subsets regulating anti-zcetylcholine-receptor-antibody formation in myasthenia gravis and characterization of suppressor T-cell factors involved.Clin Immunol Immunopathol, 1984;33(2):182-90.
[113]Pachner AR,Kantor FS.IN vitro and in vivo actions of acetylcholine receptor educated suppressor T cell lines in murine experimental autoimmune myasthenia .Clin Exp Immunol, 1984;56(3):659-68.
[114]Lisak RP,Laramore L,Levinson AI.Suppressor T cells in myasthenia gravis and antibodies to acetylcholine receptor.Ann Neurol ,1986;19(1):87-9.
[115]Cox A,Lisak RP,Skolnik P.Effect of thymectomy on blood T-cell subsets in myasthenia gravis. Ann Neurol, 1986;19(3):297-8.
[116]Mosmann TR,Cheruinski H, Bond MW.Two types of murine helper T cell clone I.Definition according to profiles of lymphokine activities and secreted proteins.J Immunol, 1986;136(7):2348-47.
[117]Fernandez-Botran R,Sanders WM.Lymphokin-mediated regulation of the proliferative response of clones of T helper 1 and Thelper 2 cells.J Exp Med.1988;168(2):543-58.
[118]Mora A,Cortes C,Mateo EM,PlaM.Myasthenia gravis.Rev Esp Anestesio Reanim,1990;37(5):284-90.
[119]Drach DB.Targeting T cells in Myasthenia gravis.Ann Neurol,1999;46(4):553-5.
[120]Asano Y,Nakayama T,KuboM,et al.Analysis of two distinct B cell zctivation Pathways mediated by a monoclonal T helper cell.Ⅱ.T helper cell secretion of interleukin-4 selectively inhibits antigen-spesific B cell activation by cognate,but not noncognate. Interzctions with T cells.J Immunol 1988;140(2):419-26.
[121]DRACHMANDB.Myasthenia gravis[J].N Engl J Med,1994;330(25):1797-1810.
[122]SOMMER N,WILLCOX N,HARCOURT GC,et al. Myasthenia thymos and thymoma are selectively enriched in acetylcholine recepter reactive T cells[J].Ann Neurol,1990;28:312-319.
[123]叶师聪，吕传真. 重症肌无力的自身免疫性及其与胸腺的关系 上海医学，1988，11（6）：366-368.
[124]Oosterhuis HJGH:Myasthenia Gravis-Clinical neurology and neurosurgery monographs,Vol.5,P51,Churchill Livingstone,Edinburgh,1984.
[125]Berrih S ,Le Brigand H,Levasseur P,et al.Depletion of helper inducer T cell after thymectomy in myasthenia gravis. Clin Immunol Immunopathol, 1983;28(2):272-81.
[126]Ragheb S,Lisak RP.The thymus and myasthenia gravis.Chest Surg Clin N Am.,2001;11(2):311-27.
[127]Mingari MG,Melioli G,Moretta A,et al.Surface markers of cloned human T cells with helper or suppressor zctivity on pokeweed mitogen-driven B cell differention.Eur J Immunol 1982;12(10):900-3.
[128]Dalakas MG,Engel WK,Mcclure JE.Identification of human thymic epithelial cells with antibodies to thymosin alpha 1 in myasthenia gravis.A nn N Y Acad Sci , 1981;377:477-85.
[129]Emilie D,Devergne O,Cohen-kaminsky S.In situ production of interleukins in hyperplastic thymus from myasthenia gravis patients.Ann N Y Acad Sci,1993;681:100-2.
[130]Levinson AI,Wheatley LM.The thymus and the pathogenesis of myasthenia
gravis.Clin Immunol immunopathol,1996;78(1):1-5.
[131]Ragheb S,Lisak RP.The thymus and myasthenia gravis.Chest Surg Clin N Am,2001;11(2):311-27.
[132]Urschel JD,Grewal RP.Thymectomy for myasthenia gravis.Postgrad Med J,1998;74(869):139-44.
[133]Oosterhuis HJ,Kuks JB.Myasthenia gravis and myasthenic syndromes.Curr Opin Neurol Neurosurg,1992;5(5):638-44.
[134]Fujii Y,Monden Y,Hashimoto J, et al.Acetylcholine receptor antibody-producing cells in thymus and lymph nodes in myasthenia gravis.Clin Immunol Immunopathol,1985;34(1):141-6.
[135]Penn AS,Schotland DL,Lamme S, et al.Antimuscle and antiacetylcholine receptor antibodies in myasthenia gravis.Muscle Nerve,1986;9(5):407-15.
[136]Lisak RP,Levinson AI,Iweiman B, et al.In vitro synthesis of IgG and antibodies to AchR by peripheral and thymic lymphocytes.Ann N Y Acad Sci,1987;505:39-49.
[137]Aarli JA,Stefansson K,Marton LS,et,al. Patients eith myasthenia gravis and thymoma have in their sera IgG autoantibodies against titin.Clin Exp Immunol,1990;82(2):284-8.
[138]Hohlfeld R.Myasthenia gravis and thymoma:paraneoplastic failure of neuromuscular transmission.Lab Invest,1990;62(3):241-3.
[139]Wekerle H ,Kelelsen UP.Intrathymic pathogenesis and dual genetic control of myasthenia gravis.Lancet,1977;1(8013):678-80.
[140]薛启冥.重症肌无力与胸腺瘤.中华神经精神科杂志，1981;14(1):26-28.
[141]杜 英，等. 重症肌无力胸腺提取液及胸腺细胞免疫活性的研究.中国免疫学杂志，1997;13,116-118.
[142]韩佐宁，马树俊，龙振洲.胸腺细胞与胸腺基质相互作用.国外医学免疫学分册，1994；6：296.
[143]杜 英，等. 重症肌无力胸腺提取液蛋白分析及其与AchR-Ab关系的研究.上海免疫学杂志，2000；20（4）：225-226.
[144]吕 良，乔 健，吕传真. 重症肌无力患者血清非Ig成分对突触前、后膜受体及其相应抗体反应的影响.上海免疫学杂志，1998；18：81.
[145]Harito AA,Goodall GJ,Horecker BL.Prothymosinα:Isolation and properities of the major immunoreactive form of thymosinα1 in rat thymus.Proc Natl Acad Sci USA,1984;81:1008.
[146]殷 伟，乔 健，吕传真.重症肌无力实验模型中胸腺细胞凋亡及其机制的研究.上海免疫学杂志，2000；20（1）：44-46.
[147]Annger M,Wintersberger W,Steiner CW, et al.High levels of Bcl-2 protein in circulating T lymphocytes but not B lymphocytes of patients with systemic lupus eerythematosus.Arthr Rheum,1994;37:1423.
[148]Siegel RM,Katsumata M,Miyashita T,et al.An analysis of apoptosis in lymphoid organs and lupus disease in murine systemic lupus erythematosus.Clin Exp Immunol,1996;105:306.
[149]Onodera j,Nakamura,S,Nagano I,et al.Upregulation of Bcl-2 protein in the myasthenic thymus.Ann Neurol,1996;39:521.
[150]Gratiet-Dans J,Ding LY,Turka LA,et al.Bcl-2 proto-oncogene expression duing human T cell deelopment:evidence for biphasic regulation.J Immunol,1993;151:83.
[151]Veis DJ,Sentman CL,Bach EA,et al.Expression of the Bcl-2 protein in murine an human thymocytes and in peripheral T lyphocyte.J Immunol,1993;151:2546.
[152]Haury M,freitas A,Hermitte V,et al.The physiology of the Bcl-2 expression in murine B lymphocytes.Oncogene,1993;8:1257.
[153]Merino R,Ding L,Veis DJ,et al.Development regulation of the Bcl-2 protein and susceptibility to cell death in B lymphocytes.EMBO J,1994,13:683.
[154]岳 岚，宋作圭，柴莹等. 获得性自身免疫性重症肌无力患者胸腺组织Bcl-2和Fas表达水平的研究.浙江医学，1999；21（6）321-323.
[155]Shiono H,Fujii Y,Okumura M,et al.Failure to down-regulate Bcl-2 protein in thymic geminal center Bcells in mythasenia gravis.Eur Immunol,1997;27:805.
[156]Moulian N,Bidault J,Truffault F,et al.Thymocyte Fas exprssion is dysregulated in myasthenia gravis patients with anti-acetylcholine recepter antibody.Blood,1997;89:3287.
[157]Masunaga A,Arai T,Yoshitake T,et al.Reduced expression of apoptosis-related antigens in from patients with myasthenia gravis.Immunol Lett,1994;39:167.
[158]Heidenreich F,Vincent A.Antibodies to ion-channel proteins in thymoma with myasthenia neuromyotonia and peripheral neuropathy.Neurology,1998;50(5):1438-5.
[159]Zhang GX,Navikas V,Link H.Cytokines and the phathogenesis of myasthenia gravis.Muscle Nerve,1997;20:543-551.
[160]刘绪宏，等.大鼠重症肌无力中枢受损时白细胞介素-1的变化.中华内科杂志，1999；38（10）660-662.
[161]Powers GD,Miller RA.Heterogeneity among T helper cells.Interleukin-2 secretion and help for immunoglobulin secretion.J Immunol,1987;139(8):2567-72.
[162]Kern DE,Lachmann LB,Greenberg PD,et al.Lyt-2+ cells .Requirements for concanvacinA-induced proliferation and interleukin2 prodution.J Immunol,1987; 137(9):2880-7.
[163]Smith JB,Talal N.Significance of self-recognition and interleukin-2 for immunoregulation,autoimmunity and cancer.Scad J Immunol 1982;16(4):269-78.
[164]Chrisdodoss P，Dauphinee M,Lindstrom J, et al.Deficient T-cell mitogen response in murine experimental autoimmune myasthenia gravis :a defect in the adherent cell population.Cell Immunol,1983;79(2):358-66.
[165]章崇杰,吴慧君，徐文桢.重症肌无力患者周围血自然杀伤细胞活性的研究。中华神经精神科杂志,1987;20(5):269-271.
[166]李震中，杨明山，高波廷，等. 重症肌无力患者血清SIL-2R水平检测.中国神经免疫学和神经病学杂志，1997；4（1）：32-35.
[167]Cohen-Kaminsky S,Jacqes Y,Aime C,et al.Follow-up of soluble interluekin-2 recepter levels after thymectomy in patients with MG Clinical Immunology and Immunopathology,1992;62(2):190.
[168]耿新杰，王守亮，王炳旭. 重症肌无力患者血清sIL-2R的检测.中国免疫学杂志，1994；1：57.
[169]Confalonieri P,Antozzi C,Cornelio F,et al.Immune activation in myasthenia gravis:soluble interleukin-2 receptor,interferon-gamma and tumor necrosis factor-alpha levels in patients serum.J Neuroimmunol.1993;48(1):33-6.
[170]Wang ZY,Link H,Huang WX,et al.T cell immunity to acetylcholine receptor and its subunits in Lewis rats over the course of experimental autoimmune myasthenia gravis.Scand J Immunol,1993;37(5):615-22.
[171]Zhang GX,Ma CG,Xiao BG,et al.Suppression of experimental autoimmune myasthenia gravis after CD8 depletion is associated with decreased IFN-gamma and IL-4 .Scand J Immunol,1995;42(4):457-65.
[172]Ma CG,Zhang GX,Xiao BG,et al.Cellular mRNA experission of interferon-gamma(IFN-gamma),IL-4 and transforming growth factor-bata(TGF-beta) in rats.nasally to lerzed againat experimental autoimmune myasthenia gravis(EAMG).Clin Exp Immunol,1996;104(3):509-16.
[173]梁丽云，马存根，丰 玲.IFN-γ、IL-4、TGF-β在诱导EAMG耐受中的作用.免疫学杂志，2000，16（4）：275-277.
[173]国 红，等. 重症肌无力胸腺和外周血抗原特异性单个核细胞IFN-γ、IL-4的转录及表达.中国神经免疫学和神经病学杂志，1999；6（6）：67-72.
[174]孙 宏，国红，许贤豪，等. 重症肌无力患者外周血乙酰胆碱受体特异性T细胞sIL-2R、IFN-γ、IL-4的表达和转录.中华神经科杂志，1998；31（2）：79-82.
[175]Asthana D,Fujii Y,Huston GE,et al.Regulation of antibody prodution by helper T cell clones in experimental autoimmune myasthenia gravis is mediated by IL-4 and antigene-specific T cell factors.Clin Immunol Immunopathol,1993;67:240-248.
[176]Cohen-Kaminsky S,Devergne O,Delatre Related Articles,et al.Interleukin-6 Overproduction by cultured thymic epithelial cells from patients with myasthenia gravis is potentially in volved in thymic myperplasia.Eur Cytokin Netw,1993;4(2):121-32.
[177]王福生.白细胞介素-6（IL-6）研究进展.国外医学免疫学分册，1990；13：169.
[178]Shimada K,Koh CS,Yanagisawa N,et al.Detection of inteleukin-6 inserumand cerebyospinal fluid of patients with neuro-immunological disease.1993;42:934.
[179]李作孝，徐文桢，章崇杰，等. 重症肌无力患者外周血单个核细胞白细胞介素-6活性变化.中国神经精神疾病杂志，1997；23（1）：20-22.
[180]刘绪宏，等. 重症肌无力乙酰胆碱受体抗体致中枢损害时IL-6水平的研究.武警医学，2000；11（4）：195-198.
[181]Taqpin V,Toulmond S,Serrano A.Increase in IL-6、and TNF levels in rat brain following traumatic lesion Influence of pre- and post- traumatic treatment with Ro5 4864,a peripher1-type(p site)benzodiazepine lingand.J Neuroimmunol,1993;42(2):177-85.
[182]Toulmond S,Vigex,Fage D.Local infusion of interleukin-6 attenuates the neurotoxic effects of NMNA on rats striatal cholinergic neurons.
[183]Valerio A,Ferrario M,Dreano M.Soluble interleukin-6(IL-6) receptor /IL-6 fusion protein enhances in vitro differentitation of puyified rat oligodendnoglial lineage cells.Mol Cell Neurosci ,2002;21(4):602-15.
[184]Shi FD,Zhang GX,Bai XF,et al.Cellular Mrna expression of interferon-gamma(IFN-gamma) IL-4 and IL-10 relates toresistance to experimental autoimmune myasthenia gravis(EAMG) in goung Lewis rats.Clin Exp Immunol,1997;108(3):523-8.
[185]侯世芳，等. 重症肌无力患者外周血干扰素-γ和白细胞介素-10分泌性T检测.中华神经科杂志，2000，33（2）：107-109.
[186]Zhang gx,Xiao BG,Bakhiet M,et al.Both CD4+ and CD8+T cells are essential to induce experimental autoimmune myasthenia gravis.J Exp Med,1996;184:349-356.
[187]Ma CG,Zhang GX,Xiao BG,et al.Cellular Mrna expression of interferon-gamma(IFN-gamma) ,IL-4and transforming growth factor-beta(TGF-beta) in rats nasally tolerized against experimental autoimmune myasthenia gravis (EAMG).Clin Exp Immunol,1996;104(3):509-16.
[188]Boritz E,Palmer BE,Livingston B.Diverse repertoire of HIV-1 p24-specific,IFN-gamma-producing CD4+ T cell clones following immune reconstitution on highly active antire troviral therapy.2003;170(2):1106-16.
[189]Zhang GX,Navikas V,Link H,et al.Cytokins and the pathogenesis of myasthenia gravis. Muscle Nerve,1997;20(5):543-51.
[190]Spurkland A,Gilhus NE,Ronningen KS,et al.Myasthenia gravis patients with thymus hyperplasia and myasthenai gravis patients with thymoma display different
HLA associations. Tissue Antigens,1991;37(2):90-3.
[191]国 红，等.重症肌无力胸腺和外周血抗原特异性单个核细胞IFN-γ、IL-4的转录及表达.中国神经免疫学和神经病学杂志，1999；6（2）：67-72.
[192]孙 宏，等. 重症肌无力患者外周血乙酰胆碱受体特异性T细胞sIL-2R、IFN-γ、IL-4的表达和转录.中华神经科杂志，1998；31（2）：79-82.
[193]Link J.Interferon-γ,IL-4 and transform growth factor-βmRNA expression in multiple sclerosis and myasthenia gravis.Acta Neurol Scand.1994;158(supple):1-58.
[194]Moiola L,Karachunski P,Protti MP,et al.Epitopes on the beta subunit of human muscle acetylcholine recepter recognized by CD4+ cells of myasthenia gravis patients and healthy subunits.J Clin Invest,1994;93:1020-1028.
[195]Zhang GX,Ma CG,Xiao BG,et al.Autoreactive T cell responses and cytokin patterns reflect resistance to experimental autoimmune myasthenia gravis in Wistar Farth rats. Eur J Immunol,1996;26(11):2552-8.
[196]Balasa B,Deng C,Lee J,et al.Interferon-gamma is necessary for the genes of acetylcholine receptor induced clinical experimental autoimmune myastnenia gravis in mice. J Exp Med,1997;186(3):385-91.
[197]Shenoy M,Baron S,Wu B,et al.IFN-alpha trentment supresses the development of experimental autoimmune myasthenia gravis .J Immunol,1995;154(11):6203-8.
[198]Benigni F,Sado S,Pennica D.Cardiotrophin-1 inhibits tumor necrosis factor production in the heart and serum of lipopolysaccharide-treated mice and vitro in mouse blood cells.Am J Pathol,1996;149(6):1847-50.
[199]Nadif R,Tedicka A,Mintz M,et al. Effect of TNF and LAT polymorphisms on biological markers of response to oxidative stimuli in coal miners:a model of gene-environmemt interaction Tumor necrosis factor and lymphotoxin alpha.J Med Genet,2003;40(2):96-103.
[200]Ares MP,Stollenuerk M,Olsson A,et al. Decreased inducibility of TNF expression in lipidloaded macrophages.BMC Immunol,2002;3(1):13..
[201]Marriott JB,Clarke IA,Dredge K,et al.Thalidomide and its anslogues have distinct and opposing effects on TNF-alpha and TNFR2 during costimulation of both CD4+ and CD8+ T cells.Clin Exp Immunol,2002;130(1):75-84.
[202]Becker J C,Dummer K,Hartmann AA,et al. Shedding of ICAM-1 from human melanoma cell lines induced by IFN-gamma and tumor necrosis factor-alpha Functional consequences on cell-mediated cytotoxicity.J Immunol,1991;147(12):4398-401.
[203]Hill ME,Ferguson DJ,Austyn JM,et al.Potent immunostimalatory dendritic cells can be cultured in bulk from progrenitors in normal infantand adult myasthenic human thymus.Immunology,1999;97(2):325-32.
[204]李作孝，等. 重症肌无力患者血清TNF水平变化及其与AchRab产生的相关性研究.中华神经科杂志，1996；29（6）：354~356.
[205]Yotota S,Geppert TD,Lipsky PE.Enhacemeht of antigen-and mitogen-induced human T lmphocyte proliferration by tumor necrosis factor-α,J Immunol,1988,140:531.
[206]Rubin LA,Nelson DL.The soluble interleukin2 recepter:biology,function and clinical application.Ann Intern Med,1990;113:619.
[207]Becker J C,Kolanus w,Lonnemuann C,et al.Human natural clones enhance in vitro antibody production by tumor necrosis factor alpha and gama interferon.Scand J Immunol,1990;32:153.
[208]Kehrl J.Thevenin C,Rieckmann P,et al.Transforming growth factor beta suppresses human Blymphocyte Ig production by inhibiting Synthesis and the Swith from the
membrone form to the secreted form of Ig mRNA.J Immunol,1991;146:4016-4023.
[209]Wahl S M,Hunt D A,Wong HL,et al.Transforming growth factor beta is apotent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation.J Immunol,1992,149:3026-3032.
[210]Chantry D,Turner m,Abney E et al.Modulation of cytokine production by transforming growth factor-β.J Immunol,1989;142:4295-4300.
[211]Link J,Fredrikson S,Olsson T,et al.Orgon-specific autoantigens induce transforming growth factor-βmRNAexpression in mononuclear cells in multiple sclerosis and myasthenia gravis.Ann Neurol,1994;35:197-203.
[212]Wang ZY,Link H,Ljungdah A.Induction of interferon-gamma,interleukin-4,and transforming growth factor-beta in rats orally tolerized against experimental autoimmune myasthenia gravis.Cell Immunol,1994;157(2):353-68.
[213]Zhang GX,Ma CG,Xiao BG,et al.Suppression of experimental autoimmune myasthenia gravis after CD8 depletion is associated with decreased IFN-gamma and IL-4.Scand J Immunol,1995;42(4):457-65.
[214]He B,Link J,Navikas V,et al.Transforming growth factor beta1 suppresses auto-antigen induced expression of pro-inflammatory cytokines but not of interleukin-10 in multiple sclerosis and myasthenia gravis .J Neuroimmunol,1995;58:21-35.
[215]Shipman GF,Bloomfield CD,Smith KA,et al.The effect of slucocorticoid therapy on glucocorticoid recepters in leukemia and lymphoma.Blood,1981,58(6):1198.
[216]Gooduin TS,Messner RP,Williams R.Inhibitors of T cell mitogenesis:effect of mitogen dose.Cellular immunol,1979;45:303.
[217]Waage A,Bakke O.Glucocorticoids suppress the production of tumor necrosis factor by lipopolysaccharide-stimulated humanmonocytes.Immunology,1988;63(2):299-302.
[218]杨晓红，等.实验性重症肌无力小鼠脾淋巴细胞糖皮质激素受体测定.川北医学院学报，1998；13（2）：14-15.
[219]Pouplard A,Battazzo GF,doniach D et al.Binding of immunoglobulins to pituitary ACTH cells.Nature,1976;261:142.
[220]Besedorsky HO,Del Rey A,Sorkin B et al.Lymphoid cells produce an immunoregulatory glucocorticoid increasing factor(GIF) acting through the pituitary gland.Clin Exp Immunol,1985;59(3):6227.
[221]刘卫彬，等. 重症肌无力患者淋巴细胞糖皮质激素受体与激素疗效依赖性的关系.中国神经精神疾病杂志，1999；25（4）：195-197.
[222]Aoki T,Drachman DB,Asher DM, et al.Attempts to immplicate viruses in myasthenia gravis.Neurology,1985;35(2):185-92.
[223]Shirkey BL,Slavin S,Vistica BP,et al.Immunomodulatory effects of linomide in animals immunized with immunopathogenic retinal antigens:dissolciation between different immune functions.Clin Exo Immunol,1997;11108(3):539-44.
[224]Caponnet to G,Rossi E,Primavera A,et al.Mycophenolate nofetil:a new immunosuppressive approach.Eur Neurol,2001;46(1):53-4.
[225]Brenner T,Timore Y,Wirguin I,et al.IN vitro synthesis of antibodies to acetylcholine receptor by Epstein-Barr Virus-Stimulated B-lympholytes derived from patients with myasthenia gravis.J Neuroimmunol,1989;24(3):217-22.
[226]Nath A,Kerman RH,Novak IS,et al.Immune studies in human immunodeficiency virus. Neurology,1990;40(4):581-3.
[227]Stefansson K,Dieperink ME,Richman DP, et al.Sharing of epitopes by bacteria and nicotinic acetylcholine receptor:a possible role in the pathogenesis of myasthenia
gravis.Ann N Y Acad Sci,1987;505:451-60.
[228]Dwyer DS,Vakil M,Kearney JF, et al.Idiotypic network connectivity and a possible cause of myasthenia gravis.J Exp Med,1986;164(4):1310-8.
[229]Martin F,Corrigan FM,Donard OF,et al.Organotin compounds in trimethyltin-treated rats and in human brain in Alzheimers disease. Human Exp Toxicol,1997;16(9):512-5.
[230]Feltkamp Tew,et al.Myasthenia gravis auto-antibodies and HLA antigens.Br Med J,1974;1:131.
[231]Compston Das,et al.Clinical pathological HLA antigen and immunological evidence for disease heterogeneity on myasthenia gravis.Brain,1980;103:579.
[232]Naeim F et al.Association of HLA-B8,DRw3 and antiacetylcholine receptor antibodies in myasthenia gravis.Tissue Antigens,1978;12:381.
[233]Keesey J,et al.Acetylcholine receptor antibody titer and HLA-B8 antigen in myasthenia gravis.Arch Neurol,1982;39:73.
[234]Kaichi Kida,et al.Heterogeneity on Myasthenia gravis:HLA,phenotypes and autoantibody responses in ocular and generalized type.Annals of Neurology,1987;21:274.
[235]许贤豪.重症肌无力—120例实验和临床观察。中华神经科杂志，1985；6：321.
[236]徐文桢，等.重症肌无力患者HLA与抗乙酰胆碱受体抗体的研究.中华神经精神科杂志，1992；25（3）：150-153.
[237]Gigliotti D,Lefvent AK,Jeddi-Tehrani,et al.Over expression of select T cell receptor V gene families within CD4+ and CD8+ T cell subsets of myasthenia gravis patients.Mol Wed ,19962(4):452-9.
[238]Theofilopoulos A N.The basis of autoimmunity:Part 1 Mechanism of aberrant selfrecognition.Immunol Today,1995;16:90.
[239]Kronenberg M,Hood L E,et al.The molecular genetics of the T-cell antigen recepter and T-cell antigen recognition.Ann Rev Immunol,1986;4:529.
[240]Christadess P,Wu B,Shenoy M,et al.TCR gene usage in experimental autoimmune myasthenia gravis pathogensis.J Immunol,1995;154:3603.
[241]Berrih-Aknin S,Aime-Sempe c,Cohen-Kaminsky S,et al.In vivo preferential usag of TCR-Vβ8 in Torpedo acetylcholine receptor immune response in the murine experimental model of myasthenia gravis.J Neuroimmunol,1995;58:191.
[242]Hohlfeld R,Wekerle H.The thymus in myasthenia gravis.Neurol Clin North Am,1994;12:331.
[243Tesch H,Holhfeld R,,Toyka KV,et al.Analysis of immunoglobulin and T cell receptor gene rearrangements in the thymus of myasthenia gravis patients.J Neuroimmunol,1989;21:169.
[244]Kawada J,Ueda Y,Sakai K,et al.Rearrangement of T cell receptor gene in thymoma with myasthenia gravis.Muscle Nerve,1994,(Supple):S187.
[245]高 枫，李晓东，陈清棠，等. 重症肌无力T细胞受体基因重排的初步研究.中国神经免役学和神经病学杂志, 1997;4(2):74-76.