Objective To analyze the relationship between tumor necrosis factor-alpha (TNFα) gene promoter -308 polymorphism and myasthenia gravis (MG) in Chinese and analyze secretion of TNFα in peripheral blood mononuclear ce...Objective To analyze the relationship between tumor necrosis factor-alpha (TNFα) gene promoter -308 polymorphism and myasthenia gravis (MG) in Chinese and analyze secretion of TNFα in peripheral blood mononuclear cells (PBMC) in MG patients. Methods A biallelic polymorphism at position -308 in the promoter of TNFα gene was screened by PCR amplification and NcoI recognition site. One hundred and twenty-three MG cases and 115 healthy controls were included in this study. MG patients were classified to different groups according to clinical type, age at onset, and sex respectively. PBMC were isolated from 20 patients and 20 healthy controls, and then cultured in the presence or absence of phytohemag- glutinin (PHA) and acetycholine receptors (AchR). The supernatants were harvested after incubation and stored until TNFα was assayed by enzyme-linked immunosorbent assay. Results The frequency of TNFα-308 allele 2 (A) was found significantly increase in MG patients and showed a trend especially in late onset (≥ 40 years) and male patients (P < 0.05). The allele A had no relationship with thymic pathogenesis in MG patients. But frequency of allele A was significantly higher in general type than in ocular type (P < 0.05). MG patients had a higher inducible level of TNFα by PHA and AchR, and could be down regulated after treatment. Conclusion Polymorphism in TNFα gene promoter -308 is associated with onset of MG. The microsatellite allele TNFα2 confer risk for the development of MG in Chinese patients. MG patients have a higher inducible level of TNFα.展开更多
Objective: To investigate the expression of both thymic regulatory T cells (CD4+CD25+Foxp3+cells, Treg) and thymic stromal lymphopoietin (TSLP) in thymomas accompanying myasthenia gravis. Methods: We used immunohistoc...Objective: To investigate the expression of both thymic regulatory T cells (CD4+CD25+Foxp3+cells, Treg) and thymic stromal lymphopoietin (TSLP) in thymomas accompanying myasthenia gravis. Methods: We used immunohistochemistry and real-time reverse trancription polymerase chain reaction (real-time RT-PCR) techniques to determine Foxp3+ Treg counts and the expression levels of Foxp3 mRNA and TSLP mRNA in thymomas of 23 MG patients and thymuses of 4 healthy controls. Results: The CD4+ Foxp3+ nTreg (natural regulatory T cells) counts in thymomas were significantly lower than those in normal thymuses (P<0.01), and the expression levels of Foxp3 mRNA and TSLP mRNA were also lower in thymomas(P<0.01). Among the thymoma types, type B1 thymoma had the highest Foxp3+ nTreg count and standard values of Foxp3 mRNA and TSLP mRNA. There was a strong positive correlation between the mRNA transcriptional levels of Foxp3 and TSLP. Conclusion: The insufficient expression of Foxp3 in thymoma, which may be caused by decreased transcription of TSLP, may result in the reduction of Tregs and cause autoimmune disorders.展开更多
To express and purify the protein coded by the TRAF-type zinc finger domain of myasthenia gravis (MG)-re-lated gene P9 ( P9-ZFD ) and to prepare P9-ZFD antiserum for detecting expression and subcellular distribution o...To express and purify the protein coded by the TRAF-type zinc finger domain of myasthenia gravis (MG)-re-lated gene P9 ( P9-ZFD ) and to prepare P9-ZFD antiserum for detecting expression and subcellular distribution of P9-ZFD protein in the skeletal muscles of patient with MG. Methods The cDNA encoding P9-ZFD was amplified by RT-PCR. The cloned P9-ZFD cDNA was ligated into pET-24a, and the P9-ZFD recombinant protein was induced via E.coli. BL21 (DE3) and purified by histidine affinity chromato-graphy. P9-ZFD antiserum was prepared and its titer and specificity were determined by ELISA and Western blot. Expres-sion and subcellular distribution of P9-ZFD protein in the skeletal muscles of MG and control were studied. Results The molecular weight of purified P9-ZFD protein was about 30 kD. Its purity was more than 95%. Antiserum specific for P9-ZFD was excellent. P9-ZFD protein is fully confined to the cytoplasm membrane of skeletal muscle cell of MG, obvious immunostaining was absent in the A, I, and Z bands of cytoplasm and no immunoreactivity was observed in the skeletal muscle cell of control. Conclusion P9-ZFD protein is expressed as a cytoplasm membrane-bound protein and has obvious distribution difference in the skeletal muscle cells of patient with MG and normal control.展开更多
Anti-bungarotoxin anti-serum,which has the internal image of nicotinicacetylcholine receptor,was used as a tool to measure anti-idiotypic antibodies toantibodies to Iigand of nicotinic acctylcholine receptor in scra f...Anti-bungarotoxin anti-serum,which has the internal image of nicotinicacetylcholine receptor,was used as a tool to measure anti-idiotypic antibodies toantibodies to Iigand of nicotinic acctylcholine receptor in scra from 81 patients withmyasthenia gravis.Enzyme-linked immunosorbcnt assay was adopted.Thc positive ratewas 46.9%(38/81).The specific cross inhibitory test with nicotinic acetylcholinereceptor was positive.Anti-idiotype antibodies to antibodies to ligand of nicotinicacetylcholine receptor in sera of different types of myasthenia gravis patients classified ac-cording to modified Osserman’s standard and myasthenia gravis patients with or withoutthymoma were comparcd in this study and the role of anti-idiotype antibodies toantibodies to Iigand of nicotinic acctylcholinc receptor in the immunity of myasthcniagravis and the possibility of thcrapeutic use of anti-idiotype antibodies arc discussed.展开更多
objective: To analyze the effects of thymectomy for children with myasthenia gravis (MG).Methods: Thirty-six children with MG were treated by thymectomy from 1984 to 1997, their age ranging from 4 to 14 years, with sy...objective: To analyze the effects of thymectomy for children with myasthenia gravis (MG).Methods: Thirty-six children with MG were treated by thymectomy from 1984 to 1997, their age ranging from 4 to 14 years, with symptom duration from 2 months to 8 years. According to Osserman’s classifica tion, 27 case belongs to class Ⅰ, 6 class Ⅱa, 2 class Ⅱb and 1 class Ⅲ. The outcome was graded as "much im proved", "improved", "unchanged" and "deteriorated or death". Results: 13. 9% of patients were much im proved, 69. 4% improved, so the better response to thymectomy (much improved or improved) is 83. 3%, which is significantly higher than the control group (without surgical treatment) 44. 8% (P<0. 001), and no one exacerbated or died. Conclusion: Thymectomy for children with MG is safe and effective, and the out come after thymectomy relates to the duration of symptoms and pathologic classification, but irrelevant to sex and age, and the follow-up results were satisfactory.展开更多
Objective: To explore the postoperative clinical characteristics and outcomes of myasthenia gravis with and without thymoma. Methods: Two hundred and forty-three patients with myasthenia gravis(MG) surgically treated ...Objective: To explore the postoperative clinical characteristics and outcomes of myasthenia gravis with and without thymoma. Methods: Two hundred and forty-three patients with myasthenia gravis(MG) surgically treated in our department from 1978 to 2003 were studied retrospectively. The clinical characteristics, complication, remissions and survival rates were compared between MG with and without thymoma. Results: The patients of MG with thymoma were significantly older (P<0.01), had shorter duration of symptom(P<0.01), and higher myasthenia crisis rates after operation(P<0.01) than those without thymoma. No difference of Osserman classification was found between the 2 groups. The complete remission rates and partial remission rates of MG with thymoma were significantly lower than those without thymoma at 1 and 3 years(P=0.049, P=0.000, P=0.015, P=0.010), but no differences at 5 years(P=0.457, P=0.699). The survival rates were lower in MG with thymoma than without thymoma(Log rank=18.58,P=0.000). Conclusion: The clinical characteristics are different between MG with and without thymoma. The remission of symptom of MG with thymoma is worse than that of MG without thymoma in the near future, but similar in the long future. In a long-term, the death rate of MG with thymoma is significantly higher than that of MG without thymoma.展开更多
Myasthenia gravis patients are hypersensitive to nondepolarizing relaxants, such as alcuronium, an intermediate-long nondepolarizing agent. This study observed the effects of alcuronium treatment in myasthenia gravis ...Myasthenia gravis patients are hypersensitive to nondepolarizing relaxants, such as alcuronium, an intermediate-long nondepolarizing agent. This study observed the effects of alcuronium treatment in myasthenia gravis patients as compared with non-MG patients during operation. Ten MG patients (Ossermann class I - IV, scheduled for thymectomy) and 10 non-MG patients (ASA class I-Ⅱ, scheduled for operation) were selected. An induction dose of alcuronium 0. 2 mg/kg and thiopental 4-6 mg/kg was given , followed by intubation and ventilation with 50% nitrous oxide in oxygen and 0.5-1. 5% ethrane. Neuromuscular transmission was monitored using an accelerogragh and degrees of neuromuscular function at different depths were recorded. There were statistically significant differences between the two groups. The effect of alloferin in the MG group was quicker and deeper.This study also found a relation between MG class and the recovery of respiration: Respiratory recovery was quicker in classes I-Ⅱthan in classes Ⅲ-Ⅳ.展开更多
文摘Objective To analyze the relationship between tumor necrosis factor-alpha (TNFα) gene promoter -308 polymorphism and myasthenia gravis (MG) in Chinese and analyze secretion of TNFα in peripheral blood mononuclear cells (PBMC) in MG patients. Methods A biallelic polymorphism at position -308 in the promoter of TNFα gene was screened by PCR amplification and NcoI recognition site. One hundred and twenty-three MG cases and 115 healthy controls were included in this study. MG patients were classified to different groups according to clinical type, age at onset, and sex respectively. PBMC were isolated from 20 patients and 20 healthy controls, and then cultured in the presence or absence of phytohemag- glutinin (PHA) and acetycholine receptors (AchR). The supernatants were harvested after incubation and stored until TNFα was assayed by enzyme-linked immunosorbent assay. Results The frequency of TNFα-308 allele 2 (A) was found significantly increase in MG patients and showed a trend especially in late onset (≥ 40 years) and male patients (P < 0.05). The allele A had no relationship with thymic pathogenesis in MG patients. But frequency of allele A was significantly higher in general type than in ocular type (P < 0.05). MG patients had a higher inducible level of TNFα by PHA and AchR, and could be down regulated after treatment. Conclusion Polymorphism in TNFα gene promoter -308 is associated with onset of MG. The microsatellite allele TNFα2 confer risk for the development of MG in Chinese patients. MG patients have a higher inducible level of TNFα.
文摘Objective: To investigate the expression of both thymic regulatory T cells (CD4+CD25+Foxp3+cells, Treg) and thymic stromal lymphopoietin (TSLP) in thymomas accompanying myasthenia gravis. Methods: We used immunohistochemistry and real-time reverse trancription polymerase chain reaction (real-time RT-PCR) techniques to determine Foxp3+ Treg counts and the expression levels of Foxp3 mRNA and TSLP mRNA in thymomas of 23 MG patients and thymuses of 4 healthy controls. Results: The CD4+ Foxp3+ nTreg (natural regulatory T cells) counts in thymomas were significantly lower than those in normal thymuses (P<0.01), and the expression levels of Foxp3 mRNA and TSLP mRNA were also lower in thymomas(P<0.01). Among the thymoma types, type B1 thymoma had the highest Foxp3+ nTreg count and standard values of Foxp3 mRNA and TSLP mRNA. There was a strong positive correlation between the mRNA transcriptional levels of Foxp3 and TSLP. Conclusion: The insufficient expression of Foxp3 in thymoma, which may be caused by decreased transcription of TSLP, may result in the reduction of Tregs and cause autoimmune disorders.
文摘To express and purify the protein coded by the TRAF-type zinc finger domain of myasthenia gravis (MG)-re-lated gene P9 ( P9-ZFD ) and to prepare P9-ZFD antiserum for detecting expression and subcellular distribution of P9-ZFD protein in the skeletal muscles of patient with MG. Methods The cDNA encoding P9-ZFD was amplified by RT-PCR. The cloned P9-ZFD cDNA was ligated into pET-24a, and the P9-ZFD recombinant protein was induced via E.coli. BL21 (DE3) and purified by histidine affinity chromato-graphy. P9-ZFD antiserum was prepared and its titer and specificity were determined by ELISA and Western blot. Expres-sion and subcellular distribution of P9-ZFD protein in the skeletal muscles of MG and control were studied. Results The molecular weight of purified P9-ZFD protein was about 30 kD. Its purity was more than 95%. Antiserum specific for P9-ZFD was excellent. P9-ZFD protein is fully confined to the cytoplasm membrane of skeletal muscle cell of MG, obvious immunostaining was absent in the A, I, and Z bands of cytoplasm and no immunoreactivity was observed in the skeletal muscle cell of control. Conclusion P9-ZFD protein is expressed as a cytoplasm membrane-bound protein and has obvious distribution difference in the skeletal muscle cells of patient with MG and normal control.
文摘Anti-bungarotoxin anti-serum,which has the internal image of nicotinicacetylcholine receptor,was used as a tool to measure anti-idiotypic antibodies toantibodies to Iigand of nicotinic acctylcholine receptor in scra from 81 patients withmyasthenia gravis.Enzyme-linked immunosorbcnt assay was adopted.Thc positive ratewas 46.9%(38/81).The specific cross inhibitory test with nicotinic acetylcholinereceptor was positive.Anti-idiotype antibodies to antibodies to ligand of nicotinicacetylcholine receptor in sera of different types of myasthenia gravis patients classified ac-cording to modified Osserman’s standard and myasthenia gravis patients with or withoutthymoma were comparcd in this study and the role of anti-idiotype antibodies toantibodies to Iigand of nicotinic acctylcholinc receptor in the immunity of myasthcniagravis and the possibility of thcrapeutic use of anti-idiotype antibodies arc discussed.
文摘objective: To analyze the effects of thymectomy for children with myasthenia gravis (MG).Methods: Thirty-six children with MG were treated by thymectomy from 1984 to 1997, their age ranging from 4 to 14 years, with symptom duration from 2 months to 8 years. According to Osserman’s classifica tion, 27 case belongs to class Ⅰ, 6 class Ⅱa, 2 class Ⅱb and 1 class Ⅲ. The outcome was graded as "much im proved", "improved", "unchanged" and "deteriorated or death". Results: 13. 9% of patients were much im proved, 69. 4% improved, so the better response to thymectomy (much improved or improved) is 83. 3%, which is significantly higher than the control group (without surgical treatment) 44. 8% (P<0. 001), and no one exacerbated or died. Conclusion: Thymectomy for children with MG is safe and effective, and the out come after thymectomy relates to the duration of symptoms and pathologic classification, but irrelevant to sex and age, and the follow-up results were satisfactory.
文摘Objective: To explore the postoperative clinical characteristics and outcomes of myasthenia gravis with and without thymoma. Methods: Two hundred and forty-three patients with myasthenia gravis(MG) surgically treated in our department from 1978 to 2003 were studied retrospectively. The clinical characteristics, complication, remissions and survival rates were compared between MG with and without thymoma. Results: The patients of MG with thymoma were significantly older (P<0.01), had shorter duration of symptom(P<0.01), and higher myasthenia crisis rates after operation(P<0.01) than those without thymoma. No difference of Osserman classification was found between the 2 groups. The complete remission rates and partial remission rates of MG with thymoma were significantly lower than those without thymoma at 1 and 3 years(P=0.049, P=0.000, P=0.015, P=0.010), but no differences at 5 years(P=0.457, P=0.699). The survival rates were lower in MG with thymoma than without thymoma(Log rank=18.58,P=0.000). Conclusion: The clinical characteristics are different between MG with and without thymoma. The remission of symptom of MG with thymoma is worse than that of MG without thymoma in the near future, but similar in the long future. In a long-term, the death rate of MG with thymoma is significantly higher than that of MG without thymoma.
文摘Myasthenia gravis patients are hypersensitive to nondepolarizing relaxants, such as alcuronium, an intermediate-long nondepolarizing agent. This study observed the effects of alcuronium treatment in myasthenia gravis patients as compared with non-MG patients during operation. Ten MG patients (Ossermann class I - IV, scheduled for thymectomy) and 10 non-MG patients (ASA class I-Ⅱ, scheduled for operation) were selected. An induction dose of alcuronium 0. 2 mg/kg and thiopental 4-6 mg/kg was given , followed by intubation and ventilation with 50% nitrous oxide in oxygen and 0.5-1. 5% ethrane. Neuromuscular transmission was monitored using an accelerogragh and degrees of neuromuscular function at different depths were recorded. There were statistically significant differences between the two groups. The effect of alloferin in the MG group was quicker and deeper.This study also found a relation between MG class and the recovery of respiration: Respiratory recovery was quicker in classes I-Ⅱthan in classes Ⅲ-Ⅳ.
