原发全身性癫痫遗传流行病学研究

本文报道１００例原发全身性癫痫家系的遗传流行病学研究结果。先证者一级亲属患病率为６．８６％，二级亲属为１．０３％；分别是对照组一级亲属的１３．８３倍和２．０８倍。原发全身性癫痫的遗传度为：一级亲属０．７５２１±０．０６７８，二级亲属０．３５９２±０．０７４６；加权平均０．５７４３±０．０５０２。说明遗传因素起重要作用。发病年龄影响因素分析表明：原发全身性癫痫有一定年龄依从性。ＥＥＧ家系分析显示，该型癫痫一级亲属癫痫样放电明显高于对照组一级亲属，提示癫痫样放电的遗传倾向。     

抑郁症患者自杀的遗传效应研究

目的：了解抑郁症患者自杀行为与遗传的关系，提供有关遗传预测的资料。方法：对近二年连续住我院符合ＣＣＭＤ－２－Ｒ抑郁症诊断标准的６３例抑郁症患者及其一级亲属进行了遗传效应的研究，以无精神疾病者２６９人为对照组。所得资料行单因素分析，用多基因阈值理论估算自杀行为的遗传率。结果：索引病例中有自杀行为者较其一级亲属高（Ｐ〈０．００１）。一级亲属中发生自杀行为的危险性较对照组高（Ｐ〈０．０１），有自杀行为的     

情感性精神障碍遗传学家系调查

目的评价情感性精神障碍的遗传效应。方法对符合国际疾病分类第１０版和中国精神疾病分类方案与诊断标准第２版修订本中情感性精神障碍诊断的１０２个先证者家系登门调查。结果共调查先证者一、二级亲属４８９８人。１０２个先证者家系精神障碍的阳性率为５８．８％，其中情感性精神障碍同病率为８５．０％，遗传率加权平均值为１０６．３％±２．４％，高发家系为１５０．７％±１４．８％。结论遗传因素在情感性精神障碍病因中具有十分重要地位，遗传方式可能是具有显性主基因的多基因遗传     

情感性障碍高发家系的遗传学调查

本文调查３０例情感性障碍高发家系的一、二、三级亲属成员共１０９６人，患各类精神疾病１０５例，患病率为９．５８％，其中情感性障碍６４例，占６０．９５％．调查资料表明，各级亲属患病率是亲缘关系越近，患病率越高，远超于群体患病率。本文还就遗传方式进行了探讨，提出情感性障碍以伴性遗传的可能性大．     

抗人乙酰胆碱受体单抗的致病性和可变区序列分析

为探讨重症肌无力（ＭＧ）和实验性自身免疫性重症肌无力（ＥＡＭＧ）的发病机制，测定了小鼠抗人肌肉乙酰胆碱受体（ＡＣｈＲ）单抗Ｇ１０对健康大鼠的致病性以及Ｇ１０可变区核苷酸序列。Ｇ１０可使健康大鼠诱导出ＥＡＭＧ，其全身肌肉ＡＣｈＲ损失率达２８．８％±１４．０％。Ｇ１０的重链可变区（ＶＨ）基因由小鼠ＰＣ７１８３种系基因编码，与ＭＯＰＣ２１ＶＨ种系基因的同源性为９７．０％。Ｇ１０的轻链可变区（ＶＬ）基因与抗ＤＮＡ抗体的ＶＬ基因同源性为９６．２％。从此结果可以看出，Ｇ１０的重链（尤其是互补决定区３）在介导ＭＧ和ＥＡＭＧ中起更重要的作用。     

100例Alzheimer病家属同病率调查报告

目的 调查Ａｌｚｈｅｉｍｅｒ病（ＡＤ）一级亲属同病率。方法 以住院ＡＤ病人的一级亲属为对象进行家访筛查。结果 １００例ＡＤ中有阳性家族史５２例，一级亲属４４６人中有ＡＤ５６例，其中５５岁以上患病率为１５．４％，６５岁以上为２０．１％，７５岁以上为２６．４％，加权平均遗传率为７３．５％。结论 ＡＤ一级亲属同病患病风险大于普通人群。     

单双相情感性障碍的家系遗传倾向研究

本文通过住院的１６９例情感性障碍先证者，就其家系成员罹患精神病情况以及某些遗传倾向进行研究分析。同时对情感性障碍的分型，临床患病等作了比较。发现３６．１％的先证者有家族精神病史，罹患病的三级亲属中，Ⅰ级亲属占６２．４％，双亲患病率为８．６％，母亲患病率显著高于父亲患病率（Ｐ＜０．００２）。提示：遗传是情感性障碍的可能病因之一，母亲患病后对其后代影响最大。单相型患者的Ⅰ级亲属患病率并不低于双相型的Ⅰ级亲属患病率。     

高发情感性障碍的遗传方式探讨

目的 探讨４５个高发情感性障碍的家系的遗传方式。方法 按中国精神疾病分类方案与诊断标准第二版（ＣＣＭＤ－２）及美国精神障碍诊断和统计手册第三版修订本（ＤＳＭ－Ⅲ－Ｒ）的情感障碍诊断标准，均符合者选为样本进行家系调查。结果 其遗传方式为多基因遗传，其加权平均遗传率为１３２．２７％，结论 认为本病可能具有一个显性主基因的多基因遗传。     

200例癔症遗传学研究

目的：探讨癔症的遗传方式。方法：对200例癔症患者家系采用多基因阈值模式理论进行了遗传方式的探讨。结果：本病有较高的家族聚集性，血缘关系越近，亲属的患病率越高，加权平均遗传率为60．5％。结论：癔症的遗传方式可能为多基因遗传。     

苏坡乡精神分裂症遗传流行学调查

本文运用遗传流行学的调查工具及方法,逐户调查了苏坡乡15岁以上人口7843人,发现精神分裂症患者48例,终身患病率为6.1％;其发病年龄以20～39岁之间为最高,全部缓解与都份缓解的病例占29.2％;精神分裂症亲属的患病率明显高于群体患病率及对照组亲属的患病率。最后就上述问题进行了讨论。     

Safety of influenza vaccination in patients with myasthenia gravis: A population‐based study

Influenza vaccination has been associated with adverse events including Guillain–Barré syndrome. Because the safety of influenza vaccination in patients with myasthenia gravis (MG) has not been established, some clinicians discourage vaccination for these patients. We explored whether the administration of influenza vaccine to patients with MG might increase the risk of myasthenic crisis. Using population‐based healthcare data from Ontario, Canada, from 1992 to 2007, we utilized the self‐matched, case‐series method of detecting adverse events following vaccination. We studied patients with established myasthenia who were hospitalized for MG within 42 weeks of influenza vaccination. We defined the primary risk interval as the 6 weeks following vaccination. Between January 1, 1992 and March 31, 2006, we identified 3667 hospital admissions for MG. No seasonal trend in MG admissions was evident. In 513 instances, hospitalization occurred within 42 weeks following vaccination in patients previously diagnosed with MG. Among these patients, 266 (52%) were men, the median age was 74 years, and 86 (17%) had previously undergone thymectomy. The estimated relative incidence of admission for MG in the primary risk interval compared with the control interval was 0.84 (95% confidence interval 0.65–1.09). We found similar results in stratified analyses according to gender, age, and thymectomy status. Vaccination of patients with MG against influenza was not found to be associated with exacerbations of the disease. Our findings do not support the practice of withholding influenza vaccination in patients with MG. Muscle Nerve, 2009     

重症肌无力病人胸腺切除术后血清自身抗体水平变化和临床转归分析

６９例重症肌无力（ＭＧ）病人行胸腺切除术，术前血清乙酰胆碱受体抗体水平均高于正常，术后半年抗体水平明显下降，胸腺增生组（２０例）尤为显著．胸腺瘤组（４９例）术前胸腺瘤相关抗体水平增高，但术后半年内无明显变化．６９例ＭＧ患者胸腺切除术后４年，症状总缓解率为７６．８１％，其中胸腺增生组９５％，胸腺瘤组６９．３９％。作者认为，对于伴有胸腺增生或胸腺瘤的ＭＧ患者，胸腺切除术是有效的，应该列为治疗的第一选择。     

Studies on the thymus from patients with multiple sclerosis and myasthenia gravis

The thymus glands which were excised for therapy (myasthenia gravis; MG) or experimental therapy (multiple sclerosis; MS) were compared to thymic biopsies from patients undergoing cardiac surgery. There was no difference in the weight or total cells of MG and MS thymuses or of the cell density of control, of MG or MS glands. Only 1 of 25 MS thymuses was hyperplastic, as were 2 of 9 of the MG thymuses and none of the controls. Several differences were noted for thymic lymphocyte proliferation to mitogenes in MS patients and to antigens in MS and MG patients. Ms thymuses had a decreased stimulation index to antithymocyte globulin and to optimal concentrations of pokeweed mitogen. Myasthenia gravis thymuses showed a significantly increased stimulation of myelin basic protein. The % B and % T cell counts were normal for the MS patients. No differences were noted in the incidence of mixed lymphocyte reactions between thymocytes and peripheral lymphocytes in the three groups. Fresh thymic lymphocytes did not suppress concanavalin A stimulated lymphocyte proliferation. It is not known if the differences in lymphocyte proliferation between MS, MG, and control thymuses represent a primary or secondary change.     

NG2 proteoglycan-expressing microglia as multipotent neural progenitors in normal and pathologic brains

Rat primary microglia (MG) acquired a multipotent property to give rise to neuroectodermal cells through two-step culture in 10 and 70% serum-supplemented media for 5 days. Such multipotent MG, called promicroglioblasts (ProMGBs), formed cell aggregates, which generated cells with neuroectodermal phenotypes shortly after their transfer into serum-free medium. As revealed by immunohistochemistry, there were a few MG expressing NG2 chondroitin sulfate proteoglycan (NG2) in the neonatal rat brain. Primary culture from the neonatal brain contained NG2+ MG, which appeared to be the source of NG2+ ProMGB aggregates. The aggregates were MG marker+/NG2+/GFAP+/NCAM+/S-100beta- and had alkaline phosphatase activity. The marked accumulation of NG2+ MG was observed close to stab wounds made in the mature rat brain. The accumulated NG2+ MG in the wound gradually decreased in number, but the cells persisted up to 150 days postlesioning. In addition, GFAP immunoreactivity increased markedly around the wound. The NG2+ MG in the wounds separated with trypsin-EDTA formed NG2+ aggregates in 70% serum-supplemented medium and then transformed into cells with neuroectodermal phenotypes in serum-free medium. Although it is difficult to separate viable neurons from mature brains, cells from stab wounds generated process-bearing beta-tubulin III+ cells in vitro easily. These data suggest that NG2+ MG in normal developing or pathologic brains are involved in the genesis or regeneration of the brain.     

Randomized,controlled trial of intravenous immunoglobulin in myasthenia gravis

We initiated a randomized, double-blinded, placebo-controlled trial of intravenous immunoglobulin (IVIG) treatment in myasthenia gravis (MG). Patients received IVIG 2 gm/kg at induction and 1 gm/kg after 3 weeks vs. 5% albumin placebo. The primary efficacy measurement was the change in the quantitative MG Score (QMG) at day 42. Fifteen patients were enrolled (6 to IVIG; 9 to placebo) before the study was terminated because of insufficient IVIG inventories. At day 42, there was no significant difference in primary or secondary outcome measurements between the two groups. In a subsequent 6-week open-label study of IVIG, positive trends were observed.     

Myasthenia Gravis : Identification of Skeletal and Heart Muscle antigens not related to the acetylcholine receptor

Myasthenia gravis (MG) is a neuromuscular disease thought to have an autoimmune etiology. The acetylcholine receptor has been considered the primary site of antibody binding; however, other muscle components may be involved in the pathogenesis of myasthenia gravis. This study describes a hypertonic sucrose extract of skeletal muscle (Muscle-HSE) that reacts with antibodies in myasthenic sera. The active component in Muscle-HSE is not the acetylcholine receptor as demonstrated by the inability of this extract to bind [125I]alpha-bungarotoxin. Muscle-HSE does, however, contain two distinct antigenic components reactive with MG sera. One antigen reacted with 70% (14/20) of myasthenic sera in the passive hemagglutination assay. This antigen was detected in the HSE of both skeletal muscle and heart, and was unaffected by treatment with Triton X-100. The second antigen reacted with 10% (2/20) of MG sera in the complement fixation assay, was unique to skeletal muscle, and was inactivated by Triton X-100.     

Generation and characterization of immortalized rat retinal microglial cell lines

Retinal microglia play an important role as resident immunocompetent and phagocytic cells in the event of injury and disease. Retinal microglia and microglia precursor transplantation show a rescue effect in ischemic retina and retinal degeneration. However, studies of retinal microglia have been hampered by the difficulty of obtaining sufficient numbers of microglia. One way to circumvent this difficulty is to establish permanent retinal microglia cell lines. In the present study, we report the generation of immortalized retinal microglia, T‐MG cells, from postnatal day 3 rat retinal tissue using a lentiviral vector encoding SV40 large T antigen. The T‐MG cells exhibited cell‐type‐specific antigens for monocyte/macrophage lineage cells, including CD11b (OX42), ED1 (OX6), and Iba1, and actively phagocytosed latex beads. In addition to primary retinal microglia, T‐MG cells also have the ability to recruit into chemokines. Treatment of T‐MG cells with lipopolysaccharide (LPS) led to increased levels of tumor necrosis factor‐α, interleukin‐1β, and inducible nitric oxide synthase. Genome‐wide microarray analysis showed a less than 1% difference in the genes between the T‐MG cells and the control primary retinal microglia. The T‐MG cells exhibited properties similar to those of the primary retinal microglia and should have considerable utility as an in vitro model for the study of retinal microglia in health and as a curative therapy and an in vivo model for the study of retinal microglia in disease. © 2014 Wiley Periodicals, Inc.     

重症肌无力单纤维肌电图测定

57例MG患者和40例健康正常人分别进行了SFEMG检查,部分患者同时进行重复电刺激和SFEMG进行比较。结果发现:MG患者SFEMG阳性率为82.5％。按MG分型:眼肌型阳性率为58.3％,全身型阳性率为100％。而重复电刺激阳性率仅为64％。同时SFEMG的个体MCD均值大小及Jitter阻滞率与病程无关,与病型和病情有关。SFEMG是诊断MG敏感的电生理检查方法。     

以咽喉部肌无力为首发表现的儿童重症肌无力六例

目的 提高临床医师对儿童期以咽喉部肌无力起病的重症肌无力(MG)临床表现的认识水平,做到及时诊断和个体化治疗.方法 分析6例以咽喉部肌无力为主要表现的儿童期MG的诊断、鉴别诊断及治疗过程.结果 在诊断儿童期MG明确后,给予规范治疗,病情迅速好转.结论 以吞咽困难、构音障碍等咽喉肌病变表现为MG唯一或主要起病症状时,应尽...     

Titin and ryanodine receptor epitopes are expressed in cortical thymoma along with costimulatory molecules

Cortical-type thymomas are associated with myasthenia gravis (MG) in 50% of the cases. MG is caused by antibodies against the acetylcholine receptors (AChR), but additional non-AChR muscle autoantibodies such as those against titin and ryanodine receptor (RyR) are found in up to 95% of MG patients with thymoma. To elucidate the induction of non-AChR autoantibodies in thymoma-associated MG, we studied cortical-type thymomas from seven thymoma MG patients, and sera from six of them. All six had titin antibodies, and four had RyR antibodies. Titin and RyR epitopes were co-expressed along with LFA3 and B7 (BB1) costimulatory molecules on thymoma antigen-presenting cells (APC) in all thymomas. In normal thymus, the staining by anti-titin, anti-RyR, anti-LFA3, and anti-BB1 antibodies was weak and occurred exclusively in the medulla and perivascularly. Our results indicate a primary autosensitization against titin and RyR antigens inside the thymoma. In MG-associated thymoma, the mechanisms involved in the initial autosensitization against titin and RyR are probably similar to those implicated in the autosensitization against AChR. In all cases, there is an overexpression of muscle-like epitopes and costimulatory molecules indicating that the T-cell autoimmunization is actively promoted by the pathogenic microenvironment inside the thymoma.