Objective To investigate the distribution and clinical manifestations of intracranial arterial occlusive lesions （IA- OLs）, and their correlation with thyroid function. Methods We enrolled 7 patients who had Graves...Objective To investigate the distribution and clinical manifestations of intracranial arterial occlusive lesions （IA- OLs）, and their correlation with thyroid function. Methods We enrolled 7 patients who had Graves＇ disease （GD） with IAOLs screened and evidenced by transcranial Doppler, then further confirmed with digital substract angiography in 2 patients and magnetic resonance angiography in 5 patients. Brain magnetic resonance imaging （MRI） was performed in all 7 patients. Three patients were followed up. Results Among 7 patients, 1 was male and 6 were females. The mean age was 32.0 ± 5.5 （ range from 11 to 49） years old. Six of them had symptoms of GD but one was asymptomatic with abnormality of I3, T4, and thyroid stimulating hormone. The lesions of intracranial arteries were symmetrical bilaterally in the intemal carotid artery system in 6 patients, as well as asymmetrical in 1 patient. Terminal internal carotid artery （TICA） were involved in all 7 patients. Middle cerebral artery （MCA） were involved in 3, anterior cerebral artery in 2, and basilar artery in 1 patient. Net-like collateral vessels and mimic moyamoya disease were observed in the vicinity of the occlusive arteries in 2 patients. All patients presented symptoms of ischemic stroke including transient ischemic attack and/or infarction while IA- OLs were found. Three patients had obvious involuntary movements. Brain MRI revealed infarctions located in the cortex, basal ganglion, or hemiovular center in 5 patients. The remaining 2 patients had normal brain MRI. The neurological symptoms were improved concomitant with relief of the thyroid function in 2 patients, while IAOLs were aggravated with deterioration of the thyroid function in 1 patient. Conclusion IAOLs in patients with GD mainly involve intracranial arteries, especially the TICA and MCA, which is similar to moyamoya disease. The neurological symptoms and severity of involved arteries may relieve while the hyperthyroidism is gradually under control.展开更多
Objective Graves’disease is the most common autoimmune thyroid disease and its prevalence and clinical manifestations are disparate between females and males.Costimulatory molecules play an essential role in regulati...Objective Graves’disease is the most common autoimmune thyroid disease and its prevalence and clinical manifestations are disparate between females and males.Costimulatory molecules play an essential role in regulating autoimmune responses.The objective of this study was to determine if expression of inhibitory molecules was correlated with treatment by dihydrotestosterone(DHT)in an in vivo BALB/c mouse model of experimental autoimmune Graves’disease.Methods Female BALB/c mice were immunized three times with thyroid stimulating hormone receptor A-subunit encoded by adenovirus to establish a Graves’disease model.Three different doses of DHT or a matching placebo were administered by implantation of slow-release pellets a week before the first immunization.Four weeks after the third immunization,the mice were euthanatized,and then the spleen and thymus were removed.Total thyroxine and free thyroxine levels in serum of mice were detected using a radioimmunoassay kit.Real-time polymerase chain reaction was performed to estimate the expression of costimulatory molecules in lymphocytes from the spleen and thymus.Flow cytometry was used to analyze the percentage of CD4^+T cells in splenic lymphocytes.Quantitative data were compared with unpaired t-tests.Correlation between two variables was analyzed using Analysis of Variance.Results Treatment with DHT can dramatically reduce total thyroxine and free thyroxine levels.Higher expression of programmed death-1 was found in the spleen of Graves’disease mice receiving 5 mg of DHT treatment(0.635±0.296 vs.0.327±0.212;t=2.714,P=0.014),similarly,T-cell immunoglobulin domain and mucin domain 3(TIM-3)in both the spleen(1.004±0.338 vs.0.646±0.314;t=2.205,P=0.022)and the thymus(0.263±0.127 vs.0.120±0.076;t=3.221,P=0.004)also increased after 5 mg of DHT treatment compared with the parallel placebo model mice.Moreover,the percentage of CD4^+T cells declined in the splenic lymphocytes of Graves’disease mice treated with 5 mg of DHT(19.90%±3.985%vs.24.05%±2.587%;t=2.804,P=0.012).A significant negative association was observed between expression of TIM-3 in the spleen and serum levels of total thyroxine(r=-0.7106,P=0.014)as well as free thyroxine(r=-0.6542,P=0.029).Conclusion This study demonstrates that DHT can ameliorate experimental autoimmune Graves’disease,which may occur by up-regulating expression of programmed death-1 and TIM-3 and inhibiting development of CD4^+T cells.展开更多
Patients with Graves’ disease (GD) have marked lymphocytic infiltration in their thyroid glands We examined the gene for the variable regions of the α chain of the Chinese T cell rece...Patients with Graves’ disease (GD) have marked lymphocytic infiltration in their thyroid glands We examined the gene for the variable regions of the α chain of the Chinese T cell receptor(V α gene) in intrathyroidal T cells to determine the role of T cells in the pathogenesis of GD and offer potential for the development of immunotherapeutic remedies for GD Methods. We used the reverse transcription and polymerase chain reaction(RT PCR) to amplify complementary DNA(cDNA) for the 18 known families of the V α gene in intrathyroidal T cells from 5 patients with Graves’ disease The findings were compared with the results of peripheral blood T cells in the same patients as well as those in normal subjects Results. We found that marked restriction in the expression of T cell receptor V α genes by T cells from the thyroid tissue of Chinese patients with GD(P<0 001) An average of only 4 6±1 52 of the 18 V α genes were expressed in such samples, as compared with 10 4±2 30V α genes expressed in peripheral blood T cells from the same patients The pattern of expressed V α genes differed from patient to patient with no clear predominance Conclusions. Expression of intrathyroidal T cell receptor V α genes in GD is highly restricted suggesting the primacy of T cells in causing the disorders展开更多
目的通过分析胎儿微嵌合体对Graves病(GD)动物模型制备的影响,探讨胎儿微嵌合体在产后GD发病中的机制。方法应用重组人Ad-TSHR289免疫BABL/c小鼠制备GD模型,随机分组分别配对致妊娠中期或分娩结束后2周。HE染色行甲状腺组织的病理学检查...目的通过分析胎儿微嵌合体对Graves病(GD)动物模型制备的影响,探讨胎儿微嵌合体在产后GD发病中的机制。方法应用重组人Ad-TSHR289免疫BABL/c小鼠制备GD模型,随机分组分别配对致妊娠中期或分娩结束后2周。HE染色行甲状腺组织的病理学检查,Real-ti me PCR测定甲状腺内Y染色体特异性基因序列SRY。结果GD动物模型的成功率在单纯免疫组为61.5%,免疫妊娠组为38.5%,免疫生育组为76.9%,三组间存在显著性差异(P<0.05)。SRY基因的检出率在GD妊娠组中为84.6%,在妊娠对照组中为62.5%,两组间存在显著性差异(P<0.05)。分娩结束后2周,SRY在GD生育组中仍有53.8%的检出率,显著高于生育对照组中的12.5%(P<0.05)。并且,甲状腺内SRY基因的相对表达量在GD成模小鼠中较未成模小鼠显著升高(妊娠组:0.82±0.07vs.0.34±0.16;生育组:0.58±0.12vs.0,P<0.05)。结论胎儿微嵌合体在BABL/c雌鼠GD成功模型中检出几率较GD未成模者更高,SRY基因的相对表达量更高,提示胎儿微嵌合体可能参与了产后GD的发病。展开更多
文摘Objective To investigate the distribution and clinical manifestations of intracranial arterial occlusive lesions （IA- OLs）, and their correlation with thyroid function. Methods We enrolled 7 patients who had Graves＇ disease （GD） with IAOLs screened and evidenced by transcranial Doppler, then further confirmed with digital substract angiography in 2 patients and magnetic resonance angiography in 5 patients. Brain magnetic resonance imaging （MRI） was performed in all 7 patients. Three patients were followed up. Results Among 7 patients, 1 was male and 6 were females. The mean age was 32.0 ± 5.5 （ range from 11 to 49） years old. Six of them had symptoms of GD but one was asymptomatic with abnormality of I3, T4, and thyroid stimulating hormone. The lesions of intracranial arteries were symmetrical bilaterally in the intemal carotid artery system in 6 patients, as well as asymmetrical in 1 patient. Terminal internal carotid artery （TICA） were involved in all 7 patients. Middle cerebral artery （MCA） were involved in 3, anterior cerebral artery in 2, and basilar artery in 1 patient. Net-like collateral vessels and mimic moyamoya disease were observed in the vicinity of the occlusive arteries in 2 patients. All patients presented symptoms of ischemic stroke including transient ischemic attack and/or infarction while IA- OLs were found. Three patients had obvious involuntary movements. Brain MRI revealed infarctions located in the cortex, basal ganglion, or hemiovular center in 5 patients. The remaining 2 patients had normal brain MRI. The neurological symptoms were improved concomitant with relief of the thyroid function in 2 patients, while IAOLs were aggravated with deterioration of the thyroid function in 1 patient. Conclusion IAOLs in patients with GD mainly involve intracranial arteries, especially the TICA and MCA, which is similar to moyamoya disease. The neurological symptoms and severity of involved arteries may relieve while the hyperthyroidism is gradually under control.
基金supported by the National Natural Science Foundation(grant number 81670725,2017.01-2020.12)Key Research and Development Project of Shaanxi Province(grant number 2017ZDXM-SF-060,2017.01-2019.12)。
文摘Objective Graves’disease is the most common autoimmune thyroid disease and its prevalence and clinical manifestations are disparate between females and males.Costimulatory molecules play an essential role in regulating autoimmune responses.The objective of this study was to determine if expression of inhibitory molecules was correlated with treatment by dihydrotestosterone(DHT)in an in vivo BALB/c mouse model of experimental autoimmune Graves’disease.Methods Female BALB/c mice were immunized three times with thyroid stimulating hormone receptor A-subunit encoded by adenovirus to establish a Graves’disease model.Three different doses of DHT or a matching placebo were administered by implantation of slow-release pellets a week before the first immunization.Four weeks after the third immunization,the mice were euthanatized,and then the spleen and thymus were removed.Total thyroxine and free thyroxine levels in serum of mice were detected using a radioimmunoassay kit.Real-time polymerase chain reaction was performed to estimate the expression of costimulatory molecules in lymphocytes from the spleen and thymus.Flow cytometry was used to analyze the percentage of CD4^+T cells in splenic lymphocytes.Quantitative data were compared with unpaired t-tests.Correlation between two variables was analyzed using Analysis of Variance.Results Treatment with DHT can dramatically reduce total thyroxine and free thyroxine levels.Higher expression of programmed death-1 was found in the spleen of Graves’disease mice receiving 5 mg of DHT treatment(0.635±0.296 vs.0.327±0.212;t=2.714,P=0.014),similarly,T-cell immunoglobulin domain and mucin domain 3(TIM-3)in both the spleen(1.004±0.338 vs.0.646±0.314;t=2.205,P=0.022)and the thymus(0.263±0.127 vs.0.120±0.076;t=3.221,P=0.004)also increased after 5 mg of DHT treatment compared with the parallel placebo model mice.Moreover,the percentage of CD4^+T cells declined in the splenic lymphocytes of Graves’disease mice treated with 5 mg of DHT(19.90%±3.985%vs.24.05%±2.587%;t=2.804,P=0.012).A significant negative association was observed between expression of TIM-3 in the spleen and serum levels of total thyroxine(r=-0.7106,P=0.014)as well as free thyroxine(r=-0.6542,P=0.029).Conclusion This study demonstrates that DHT can ameliorate experimental autoimmune Graves’disease,which may occur by up-regulating expression of programmed death-1 and TIM-3 and inhibiting development of CD4^+T cells.
文摘Patients with Graves’ disease (GD) have marked lymphocytic infiltration in their thyroid glands We examined the gene for the variable regions of the α chain of the Chinese T cell receptor(V α gene) in intrathyroidal T cells to determine the role of T cells in the pathogenesis of GD and offer potential for the development of immunotherapeutic remedies for GD Methods. We used the reverse transcription and polymerase chain reaction(RT PCR) to amplify complementary DNA(cDNA) for the 18 known families of the V α gene in intrathyroidal T cells from 5 patients with Graves’ disease The findings were compared with the results of peripheral blood T cells in the same patients as well as those in normal subjects Results. We found that marked restriction in the expression of T cell receptor V α genes by T cells from the thyroid tissue of Chinese patients with GD(P<0 001) An average of only 4 6±1 52 of the 18 V α genes were expressed in such samples, as compared with 10 4±2 30V α genes expressed in peripheral blood T cells from the same patients The pattern of expressed V α genes differed from patient to patient with no clear predominance Conclusions. Expression of intrathyroidal T cell receptor V α genes in GD is highly restricted suggesting the primacy of T cells in causing the disorders
文摘目的通过分析胎儿微嵌合体对Graves病(GD)动物模型制备的影响,探讨胎儿微嵌合体在产后GD发病中的机制。方法应用重组人Ad-TSHR289免疫BABL/c小鼠制备GD模型,随机分组分别配对致妊娠中期或分娩结束后2周。HE染色行甲状腺组织的病理学检查,Real-ti me PCR测定甲状腺内Y染色体特异性基因序列SRY。结果GD动物模型的成功率在单纯免疫组为61.5%,免疫妊娠组为38.5%,免疫生育组为76.9%,三组间存在显著性差异(P<0.05)。SRY基因的检出率在GD妊娠组中为84.6%,在妊娠对照组中为62.5%,两组间存在显著性差异(P<0.05)。分娩结束后2周,SRY在GD生育组中仍有53.8%的检出率,显著高于生育对照组中的12.5%(P<0.05)。并且,甲状腺内SRY基因的相对表达量在GD成模小鼠中较未成模小鼠显著升高(妊娠组:0.82±0.07vs.0.34±0.16;生育组:0.58±0.12vs.0,P<0.05)。结论胎儿微嵌合体在BABL/c雌鼠GD成功模型中检出几率较GD未成模者更高,SRY基因的相对表达量更高,提示胎儿微嵌合体可能参与了产后GD的发病。
