癫痫患儿的免疫功能及免疫球蛋白辅助治疗的初步研究

目的：探讨癫痫患儿的免疫功能状态及免疫球蛋白辅助治疗的疗效。方法：测定５４例癫痫患儿血中ＩｇＧ、ＩｇＡ、ＩｇＭ、Ｓ３及Ｔ细胞亚群，与正常对照组比较；对１４例常规抗癫痫治疗效果不佳者加用免疫球蛋白辅助治疗，观察疗效。结果：癫痫患儿血清ＩｇＧ降低（Ｐ＜０．０５），ＩｇＡ降低（Ｐ＜０．０１），ＩｇＭ及Ｃ３正常，ＣＤ３、ＣＤ４降低（Ｐ＜０．０５），ＣＤ８升高（Ｐ＜０．０１），ＣＤ４／ＣＤ８降低（Ｐ＜０．０５），免疫球蛋白辅助治疗有效率５７．２％。结论：癫痫患儿存在免疫功能紊乱，提示免疫机制参与了癫痫发病机制；免疫球蛋白辅助治疗癫痫有效。     

重症肌无力患者若干临床问题探讨（附10例分析）

报告１０例ＭＧ病人均检测了周围血淋巴细胞计数、血清免疫球蛋白（ＩｇＧ、ＩｇＡ、ＩｇＭ）、补体Ｃ３、ＣＨ５０、Ｅ－玫瑰花结试验（ＥＲＦＴ）和淋巴细胞转换试验（ＬＴＴ），同时还测定血丙酮酸及酶谱（ＧＯＴ、ＬＤＨ、ＣＰＫ），并设３０例正常对照。ＭＧ组与对照组比较，除ＥＲＦＴ（Ｐ＜０．００１）、ＧＯＴ（Ｐ＜０．０１）、ＣＰＫ（Ｐ＜０．０１）、及ＬＤＨ（Ｐ＜０．０５）有差异外，余诸项均无统计学意义、提示一般血清免疫学或补体测定对ＭＧ诊断无特异性意义，结合文献复习对ＭＧ患者若干临床问题分别进行讨论。     

夏科-马里-图思病Cx32、MPZ和PMP22基因点突变的特点

目的研究我国夏科马里图思病（ＣＭＴ）Ｃｘ３２、ＭＰＺ和ＰＭＰ２２基因点突变的特点。方法应用聚合酶链反应单链构象多态性（ＰＣＲＳＳＣＰ）结合ＤＮＡ序列分析检测３０个ＣＭＴ家系的患者及５０名非血缘关系的正常对照的Ｃｘ３２、ＭＰＺ和ＰＭＰ２２基因的编码外显子。结果４个家系（３个为Ｘ连锁隐性遗传）有４种不同的Ｃｘ３２基因点突变（１３．３％）,其中１个家系为１８８位的苏氨酸被丙氨酸置换是未见报道的新突变。１个家系（３．３％）有ＭＰＺ基因点突变,未发现ＰＭＰ２２基因的点突变。结论Ｃｘ３２、ＭＰＺ和ＰＭＰ２２基因的点突变占ＣＭＴ致病原因的１６．７％。我国也存在不少Ｘ连锁遗传的家系（＞１０．０％）,对可疑的家系（家系中患者无男传男的现象）应首先进行Ｃｘ３２基因的点突变检测。我国的ＣＭＴ发病率低可能与其基因突变特点有关。     

脑血管疾病与动态血压监测

采用动态血压监测技术（ＡＢＰＭ）观察２４０例脑血管病（ＣＶＤ）患者和４０名正常成人。其中脑动脉粥样硬化４６例。短暂性脑缺血发作（ＴＩＡ）２８例，脑出血３６例，脑血栓形成４０例，腔隙梗塞９０例。ＡＢＰＭ监测结果显示：正常人血压波动呈长柄“杓”型，少数正常人（２．５％）昼夜节律消失。２４０例ＣＶＤ患者ＡＢＰＭ异常者２２８例（９５．０％），其中平均收缩压（ＭＳＢＰ），平均舒张压（ＭＤＢＰ）超过正常值者１     

人脑胶质瘤细胞多药耐药性的形成及其耐药特性的研究

目的探讨人脑胶质瘤细胞多药耐药性（ＭＤＲ）的形成规律及其耐药特性。方法采用长春新碱（ＶＣＲ）在体外对人脑胶质瘤ＢＴ３２５细胞持续诱导获得了表现为ＭＤＲ特征的人脑胶质瘤细胞模型．以ＭＴＴ法测定胶质瘤细胞增殖，透射电镜行超微结构研究，通过流式细胞仪，检测培养的胶质瘤细胞与３２例术后胶质瘤新鲜组织标本中Ｐ－糖蛋白的表达。结果耐药的胶质瘤细胞ＢＴ３２５／ＶＣＲ对长春新碱的耐受程度为其亲本细胞的２４倍，对阿霉素、威猛交叉耐药，对５－氟脲嘧啶敏感。透射电镜下见ＢＴ３２５／ＶＣＲ细胞常染色质明显，线粒体丰富，粗面内质网增多。研究表明ＢＴ３２５／ＶＣＲ表现为Ｐ－糖蛋白介导的典型ＭＤＲ。胶质瘤新鲜组织标本中，Ｐ－糖蛋白表达阳性率为３７５％（１２／３２），同肿瘤的恶性程度呈正相关（Ｐ＜０．０１）。结论长春新碱能够诱导人脑胶质瘤细胞产生Ｐ－糖蛋白介导的典型ＭＤＲ。胶质瘤中多药耐药基因产物Ｐ－糖蛋白表达的阳性率同肿瘤的恶性程度呈正相关。应用流式细胞仅能早期发现耐药细胞，具有临床推广价值。     

格林-巴利综合征患者脑脊液抗P2蛋白IgG抗体增高

用ＥＬＩＳＡ方法，检测３６例格林－巴利综合征（ＧＢＳ）患者和４０例其他神经病（ＯＮＤ）患者的血清和脑脊液及４０例健康对照（ＮＣ）血清标本的抗Ｐ２蛋白ＩｇＧ和ＩｇＭ抗体。结果发现：ＧＢＳ和ＯＮＤ血清抗Ｐ２Ｉｇ６和ＩｇＭ抗体与ＮＣ血清比较无明显差异（Ｐ＞０．０５）。ＧＢＳ脑脊液抗Ｐ２ＩｇＧ抗体明显高于ＯＮＤ（Ｐ＜０．０５），而抗Ｐ２ＩｇＭ抗体则两者无显著差异（Ｐ＞０．０５）。     

多发性肌炎和皮肌炎患者肌肉组织中组织相容性白？…

目的 检测多发性肌炎（ＰＭ），皮肌炎（ＤＭ）和非肌炎患者肌肉组织中组织相容性白细胞，Ｉ，Ⅱ类抗原（ＨＬＡ－Ｉ，Ⅱ）分子，探讨ＰＭ和ＤＭ的发病机制，方法 用链菌素亲生物蛋白－过氧化物酶连结技术对１７例已确诊的ＰＭ和ＤＭ患者，７例非肌炎患者肌肉组织染色观察。结果 ＨＬＡ－１和ＨＬＡ－Ⅱ类分子在肌炎组的阳性率分别是８８．２４％和６４．７１％，对照组为阴性，它们主要沉积在肌纤维表面，单核细胞，毛细血管和小     

脑脊液髓鞘碱性蛋白抗体检测对格林—巴利综合 …

目的 探讨格林－巴利综合征（ＧＢＳ）中枢神经髓鞘的免疫性损伤，方法ＧＢＳ患者２０例，神经系统其它疾病组（ＯＮＤ）２０例，非神经系统疾病手术者３３例，以酶联免疫吸附法检测了７３份脑脊液（ＣＳＦ）中髓鞘碱性蛋白ＩｇＧ（ＭＢＰ－ＩｇＧ）。结果 ＧＢＳ患者，ＯＮＤ患者和非神经系统疾病手术者ＣＳＦ中ＭＢＰ－ＩｇＧ阳性经分别为５５％，３０％和９．１％，ＧＢＳ患者ＣＳＦ中ＭＢＰ－ＩｇＧ阳性率与发病天线有关，结论     

PERIFASCICULAR EXPRESSION OF THE NEURAL CELL ADHESION MOLECULE IN INTERSTITIAL MYOSITIS

（１）目的：突发性多发性肌炎（ＩＰＭ）、皮肌炎（ＤＭ）和包含体肌炎（ＩＢＭ）在形态学上定义明确，但仅有间质性肌炎的诊断标准不够明确。为了确定ＩＢＭ形态学上的特征，作者用光镜试图探索肌纤维束周Ｌｅｕ１９抗原表达对ＩＢＭ的诊断意义。（２）方法：１５例无肌无力的正常对照，１２例ＩＰＭ，１４例ＤＭ，２６例ＩＢＭ，８例坏死性血管炎（ＮＶ），１５例神经性肌萎缩（ＮＭ），作肌肉活检。除作常规光镜检查外，还作免疫组化研究，用小鼠抗Ｌｅｕ１９、Ｌｅｕ２ａ、ＣＤ４、ＣＤ１６、ＣＤ２２、ＣＤ６８、Ｃ５ｂ－９单克隆抗体作一抗，再用碱性磷酸酶抗碱性磷酸酶法显色。（３）结果：肌纤维束周Ｌｅｕ１９抗原表达阳性率：ＩＢＤ、ＤＭ和ＮＶ依次为８５％、１００％和１００％，而正常对照、ＮＭ均为０％。（４）结论：在其它方面正常而有肌纤维束周Ｌｅｕ１９抗原表达是ＩＢＭ的病理学特征，所以可能有诊断价值。     

一氧化氮与帕金森病小鼠模型神经损害的研究

目的　研究一氧化氮（ＮＯ） 在帕金森病（ＰＤ）小鼠模型神经损害中的作用。方法　用比色分析、高效液相色谱电化学及免疫组化法检测１甲基４苯基四氢吡啶（ＭＰＴＰ）和７硝基吲唑（７ＮＩ）对Ｃ５７ＢＬ小鼠纹状体一氧化氮合酶（ＮＯＳ） 活性,多巴胺（ＤＡ）、二羟基苯乙酸（ＤＯＰＡＣ）、高香草酸（ＨＶＡ） 水平和酪氨酸羟化酶（ＴＨ） 免疫阳性神经纤维的影响。结果　注射ＭＰＴＰ后Ｃ５７ＢＬ小鼠纹状体ＮＯＳ活性增加,７ＮＩ能明显抑制ＭＰＴＰ引起的ＮＯＳ活性的升高（ 分别为０ ．９３ ±０．２４ 和０．５４ ±０．１６,ｎｍｏｌ·ｍｉｎ－１·ｇ－１ 组织,Ｐ＜０．０１） 。７ＮＩ能明显减轻ＭＰＴＰ引起的Ｃ５７ＢＬ小鼠纹状体ＤＡ（ 分别为０ ．８ ±０ ．２ 和６．８±０．５,μｇ／ｇ 组织,Ｐ＜０．０１） 、ＤＰＯＡＣ（ 分别为０．３ ±０．１ 和０ ．９ ±０ ．３ ,μｇ／ｇ 组织,Ｐ＜ ０ ．０１）、ＨＶＡ（分别为０．４±０．２ 和０．９ ±０ ．２,μｇ／ｇ 湿组织,Ｐ＜ ０．０１） 的降低及ＴＨ 阳性神经纤维损害。结论神经元来源的ＮＯ 参与了ＭＰＴＰ的毒性机制,神经元型ＮＯＳ抑制剂可能有益于ＰＤ的治疗。     

Expression of tissue inhibitor of metalloproteinase-1 in progression muscular dystrophy

Objective Tissue inhibitor of metalloproteinase-1(TIMP-1) is a multifunctional protein that has the capacity to modify cellular activities and to modulate matrix turnover. This paper revealed the contributive role of TIMP-1 in progressive muscular dystrophy (PMD). Methods We examined the expression and cellular localization of TIMP-1 protein using biopsied frozen muscle from patients with Duchenne muscular dystrophy ( DMD) , Becker muscular dystrophy (BMD) , congenital muscular dystrophy (CMD) by immunohistochemistry, double immunofluorescence and Western blot analysis. Results The results of immunohistochemistry and double immunofluorescence showed that TIMP-1 was positive only in vascular endothelial cells of normal muscles. Immunohistochemistry and Western blot analysis showed that the staining intensity was distinctly increased in some dystrophic muscles of PMD for TIMP-1. Double immunofluorescence revealed that TIMP-1 strongly expressed in the regenerating muscle fibers, macrophages and macrophage infiltrating necrotic fibers. Some activated fibroblasts in endomysium and perimysium of DMD and CMD muscles were also positive for TIMP-1. Conclusion The functional consequence of overexpression of TIMP-1 in the dystrophic muscles is unknown, but the elevated local expression of TIMP-1 in diseased muscles of PMD and their distinct distribution pattern provide evidence that TIMP-1 may participate in the pathogenesis of PMD.     

Expression of tissue inhibitor of metalloproteinase-1 in progression muscular dystrophy

Objective Tissue inhibitor of metalloproteinase-1 （TIMP-1） is a muhifunctional protein that has thc capacity to modify cellular activities and to modulate matrix turnover. This paper revealed the contributive role of TIMP-1 in progressive muscular dystrophy （PMD）. Methods We examined the expression and cellular localization of TIMP-1 protein using biopsied frozen muscle from patients with Duchenne muscular dystrophy （DMD）, Becker muscular dystrophy （BMD） , congenital muscular dystrophy （CMD） by immunohistochemistry, double immunofluorescence and Western blot analysis. Results The results of immunohistochemistry and double immunofluorescence showed that TIMP-1 was positive only in vascular endothelial cells of normal muscles. Immunohistochemistry and Western blot analysis showed that the staining intensity was distinctly increased in some dystrophic muscles of PMD for TIMP-1. Double immunofluorescence revealed that TIMP-1 strongly expressed in the regenerating muscle fibers, macrophages and macrophage infiltrating necrotic fibers. Some activated fibroblasts in endomysium and perimysium of DMD and CMD muscles were also positive for TIMP- 1. Conclusion The functional consequence of overexpression of TIMP-1 in the dystrophic muscles is unknown, but the elevated local expression of TIMP-1 in diseased muscles of PMD and their distinct distribution pattern provide evidence that TIMP-1 may participate in the pathogenesis of PMD.     

Pentose phosphate pathway in neuromuscular diseases--evaluation of muscular glucose 6-phosphate dehydrogenase activity and RNA content]

There have been several reports concerning elevated glucose 6 phosphate dehydrogenase (G6PDH), the rate-limiting enzyme of pentose phosphate pathway (PPP), in experimental muscle disturbances. PPP produces ribose, a substrate of RNA, and NADPH which is a cofactor of fatty acid synthesis. PPP also has a role of by-path pathway of glycolysis. Then, we evaluated G6PDH activity and RNA content in biopsied quadriceps muscle. The subjects were muscles from 23 neurogenic amyotrophy, 54 myopathy including 19 progressive muscular dystrophy (PMD), and 10 controls whose muscle was obtained at orthopedic surgery. Neurogenic amyotrophy consisted of 12 amyotrophic lateral sclerosis (ALS), 4 spinal muscular atrophy and 7 peripheral nerve disorders. Myopathy were 3 Duchenne dystrophy, 2 congenital muscular dystrophy, 8 limb-girdle type dystrophy, 6 facio-scapular +-humeral muscular dystrophy, 6 myotonic dystrophy, 6 mitochondrial myopathy, 5 endocrinological myopathy, 3 hypokalemic myopathy, 8 polymyositis and 4 other inflammatory myopathy. The assays of G6PDH and RNA were performed after Glock's and Fleck's methods, respectively. The control values were 3.6 +/- 0.8 nmol formed NADPH/mg protein/min (M +/- SD) in G6PDH and 0.69 +/- 0.17 micrograms/mg non-collagen protein in RNA. Most cases of PMD, as well as some cases of ALS, hyperthyroidism, mitochondria hypokalemic myopathy, inflammatory myopathy showed increased values (beyond M + 2SD of control) both in G6PDH and RNA. There were significant positive correlations between G6PDH activity and RNA content in PMD and motor neuron disease. Myotonic dystrophy showed normal values in both G6PDH and RNA. Half number of cases of mitochondrial myopathy demonstrated increased G6PDH alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Presence of immunoreactive beta-endorphin in human brain tumor cyst fluids

The authors report the muscular and humoral immunological abnormalities found in a family with progressive external ophthalmoplegia (PEO) of the “pure” form. Serum circulating immune complexes as determined by the polyethylen glycol (PEG) test and double radial immunodiffusion (DRID) were positive for IgG in both cases studied and for IgM and Clq for the propositus. In the latter circulating auto-antibodies against smooth muscle were also present. Immunohistochemical studies on striated muscle of the propositus showed positive perivascular IgG and IgM staining and IgG in the sarcolemma-basement membrane complex. It is suggested that in this family a genetically inherited abnormal immune response to the muscular blood vessel wall has induced vascular injury and ultimately chronic ischemic muscular damage. This is consistent with the view that PEO is a clinical syndrome, i.e. the expression of various defects affecting primarily or secondarily the energy metabolism of the muscular tissue.     

Selective type II muscle fiber hypertrophy in severe infantile spinal muscular atrophy

The diagnostic muscle biopsy finding in severe infantile spinal muscular atrophy (Werdnig-Hoffmann disease, SMA type 1) is considered to be large-group atrophy with isolated clusters of hypertrophic type I myofibers. We present a unique case of severe infantile spinal muscular atrophy with selective hypertrophy of type II myofibers. A male infant presented at age 2 months with breathing difficulties and by age 4 months was hypotonic and weak. Electromyography revealed denervation in all extremity muscles, and nerve conduction velocities were normal but with small compound muscle action potentials. Quadriceps muscle biopsy revealed many hypertrophied type II myofibers (myofibers with a mean least diameter of 25.4 microns). In contrast, the largest type I myofibers were 20 microns in least diameter (mean diameter, 14.9 microns), and there was a normal-size population of type II fibers (mean diameter, 15.7 microns). In addition, sheets of atrophic type I and type II fibers averaged 2.0 microns in least diameter. Sural nerve biopsy was normal. Breathing difficulties progressed, with death ensuing at age 5 1/2 months. Autopsy revealed atrophy of ventral spinal roots with normal dorsal roots. There was loss of anterior horn cells, while remnant neurons were reduced in size. No other pathologic changes were identified. This case indicates that in severe infantile spinal muscular atrophy, relative sparing of the motor units with type II myofibers may occur.     

Pelizaeus-Merzbacher disease: cellular hypersensitivity to ultraviolet light.

We report two connatal cases of Pelizaeus-Merzbacher disease (PMD) with cellular ultraviolet (UV)-hypersensitivity. We studied the UV-sensitivity of cultured fibroblast cells derived from these PMD cases, as compared with UV-sensitive Cockayne syndrome (CS) and xeroderma pigmentosum (XP) cells as positive controls. The ability of the PMD cells to form colonies after UV irradiation was intermediate between those of CS cells and normal controls. There were no differences in both colony-forming ability after x-ray irradiation and unscheduled DNA synthesis (UDS) activity after UV irradiation between the PMD cells and the control cells. These cytological results suggest the possibility that a DNA defect might be involved in PMD.     

Serum muscle-specific enolase in progressive muscular dystrophy and other neuromuscular diseases

Serum muscle-specific enolase (MSE, ββ and αβ enolases) levels were determined in 162 patients with progressive muscular dystrophy (PMD) and other neuromuscular diseases by means of an enzyme immunoassay method. The relationships were examinated between serum MSE, creatine kinase (CK) and other markers of muscle disease.Serum MSE was strikingly increased in Duchenne muscular dystrophy, and this elevation was more prominent in younger patients. Serum MSE was also increased in other types of PMD and certain other diseases. Serum MSE showed the highest correlation with CK. In the PMD group, the frequency of cases with elevated MSE was the same as in CK.These results indicated that serum MSE may well be a specific marker of muscle disease on a par with CK.     

Muscle coenzyme Q: a potential test for mitochondrial activity and redox status

The aim of this study is to determine whether coenzyme Q (CoQ) muscle concentrations and redox state are associated with pathologic changes in muscle biopsy specimens. Skeletal muscle biopsies were collected (January 2002-February 2004) and underwent pathologic evaluation. Quadriceps specimens (n = 47) were stratified accordingly: Group 1, controls without evidence of pathologic abnormalities; Group 2, type I myofiber predominance; Group 3, type II myofiber atrophy; Group 4, lower motor unit disease; and Group 5, muscular dystrophy. Ubiquinol-10, ubiquinone-10, total coenzyme Q10 (CoQ10), coenzyme Q9 (CoQ9), total CoQ (CoQ9+CoQ10) concentrations were analyzed in biopsy muscle by high-performance liquid chromatography. Ubiquinone-10, total CoQ10, and total CoQ concentrations were significantly decreased in Group 5. Significant positive correlations (r congruent with 0.40) were found between muscle ubiquinone-10, total CoQ10, and total CoQ concentrations vs the percentage of myofibers having subsarcolemmal mitochondrial aggregates. CoQ redox ratio and the fraction CoQ9/total CoQ were negatively correlated with subsarcolemmal mitochondrial aggregates. A significant correlation (r = 0.328) also occurred between ubiquinol-10 concentration and citrate synthase activity. This study suggests that total CoQ concentration provides a new method for estimating mitochondrial activity in biopsy muscle; and that the muscle CoQ test is feasible and potentially useful for diagnosing CoQ deficiency states.     

Slow-type C-protein in dystrophic chicken fast pectoralis muscle

C-protein isoform expression in hereditary dystrophic chicken skeletal muscle was compared with that in normal chicken muscle during postnatal development by immunocytochemical and immunoblot methods. In the pectoralis muscle (PM) of both normal and dystrophic chicken, slow- and fast-type C-proteins were coexpressed in the vast majority of myofibers at neonatal age, but the slow C-protein disappeared, leaving continued expression of only the fast-type C-protein as muscle development progressed up to 2 weeks posthatch. In the dystrophic chicken PM, however, myofibers containing slow-type C-protein reappeared about 1 month posthatch and increased in number with the progression of muscular dystrophy. We conclude that C-protein isoform expression in dystrophic myofibers resembles that in neonatal myofibers and that the expression of slow-type C-protein can be seen as a marker for chicken muscular dystrophy.     

Subacute sclerosing panencephalitis: influence of the clinical course and treatment with isoprinosine on non-specific cell-mediated and humoral immunity

Cell-mediated and humoral immunity were studied in 30 patients with subacute sclerosing panencephalitis (SSPE). Marked changes in cell-mediated immunity were observed, manifested as a decrease in total lymphocyte count, decrease of proportion of T cells forming late E rosettes, depression in lymphocyte blastogenesis, production of migration inhibition factor and delayed-type skin reactivity. The humoral immune responses was not so markedly changed and only increased levels of serum IgG, IgM and the C3c fragment of complement were noticed. The changes in immunity were more pronounced in patients with a more advanced stage of the disease. 19 patients were investigated 3 times at 7-week intervals during treatment with isoprinosine. In the group of patients (10 cases) whose clinical status was rapidly deteriorating, a marked decline of cell-mediated immunity was observed. In the group of patients showing a stationary course of the disease, cellular immunity was improving. The mechanism of the disturbances of non-specific immunity in SSPE and the influence of isoprinosine on the immune answer are discussed.