MMP-2、MMP-9基因多态性与缺血性脑卒中临床分型及预后

目的探讨基质金属蛋白酶2(Matrix Metalloproteinase-2,MMP-2)基因C1306T、C735T和MMP-9基因C1562T多态性位点与缺血性脑卒中的关系。方法采用限制性片段长度多态性分析技术,检测缺血性脑卒中组232例和健康对照组235例MMP-2基因C1306T、C735T和MMP-9基因C1562T多态的分布。结果缺血性脑卒中组和对照组MMP-2 C1306T基因型和等位基因频率分布无统计学意义。在动脉粥样硬化性血栓性脑梗死组MMP-9 C1562T的CT+TT基因型频率和T等位基因频率、MMP-2 C735T的CC基因型频率和C等位基因频率明显高于对照组(P<0.05),而在脑栓塞组、腔梗组差异无统计学意义(P>0.05)。多因素Logistic回归分析,MMP-2、MMP-9不同基因型别与缺血性脑卒中预后无显著相关性(P>0.05)。结论 MMP-2 C735T的C等位基因、MMP-9 C1562T的T等位基因是动脉粥样硬化性血栓性脑梗死的遗传易感基因之一。MMP-2、MMP-9基因多态性与缺血性脑卒中预后无关。     

基质金属蛋白酶-9基因R668Q多态性与动脉粥样硬化性脑梗死初发及复发相关性研究

目的研究基质金属蛋白酶-9(MMP-9)基因R668Q多态性与动脉粥样硬化性脑梗死初发及复发的相关性。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析法对初发脑梗死350例,复发脑梗死340例,正常对照组360例患者的MMP-9基因R668Q多态性进行分析。采用ELISA法检测MMP-9的含量,对结果进行比较。结果与正常对照组比较,初发脑梗死组及复发脑梗死组高血压病、吸烟的比率及LDL-C、血清MMP-9水平显著升高(均P0.05)。复发脑梗死组LDL-C及血清MMP-9水平显著高于初发脑梗死组(均P0.01)。Logistic回归分析显示,血浆MMP-9水平增高是脑梗死初发的独立危险因素(OR=1.336,95%CI:1.031~1.072,P=0.028),但不是脑梗死复发的独立危险因素(OR=0.609,95%CI:0.428~1.006,P0.05)。三组MMP-9基因R668Q基因型(χ~2=0.625,P0.05)和等位基因(χ~2=0.424,P0.05)的频率比较,差异无统计学意义。多变量Logistic回归分析显示,MMP-9 R668Q基因与脑梗死初发及复发均无明显相关性(OR=0.770,95%CI:0.952~1.541,P0.05;OR=0.765,95%CI:0.577~1.376,P0.05)。结论 MMP-9基因R668Q多态性与动脉粥样硬化性脑梗死初发及复发无明显相关性。     

中性内肽酶基因C159T多态性与阿尔茨海默病关联的初步研究

目的 观察中性内肽酶(neprilysin,NEP)C159T多态在广东地区汉族老年人中的分布,探讨其与晚发阿尔茨海默病(AD)的相关性.方法 以91例晚发AD患者和97名正常老年人为对照进行病例-对照研究.用聚合酶链反应-限制性片段长度多态性方法(PCR-RFLP)分析NEP基因C159T多态性和载脂蛋白E(apoE)基因多态性.结果 AD组C159T多态T等位基因频率较对照组降低(23.2%vs 25.3%,χ2=184.96,P<0.05),而两组间基因型频率差异无统计学意义(P>0.05).AD组apoE等位基因ε4与AD成正关联(19.2%vs 8.2%,OR=2.648,χ2=9.66,P<0.05).无论是否携带ApoEε4,C159T各基因型和等位基因分布在两组间差异均无统计学意义(P>0.05).结论 NEP基因C159T多态C等位基因可能与晚发AD关联,未发现APOEε4与该多态性存在协同效应.     

脑源性神经营养因子基因C270T多态性与儿童精神分裂症的关系

目的 探讨脑源性神经营养因子(BDNF)基因C270T多态性与儿童精神分裂症的关系.方法 采用病例对照研究,用聚合酶链反应-限制性片段长度多态性方法,分析204例儿童精神分裂症患者和210名健康对照的BDNF基因C270T多态性;进行阳性与阴性症状量表(PANSS)评定,用Andremson阳性与阴性精神分裂症分型标准将患者分为阴性症状为主型(阴性组)和阳性症状为主型(阳性组).结果 ①患者组和对照组间BDNF基因C270T多态性的基因型频率差异有统计学意义(χ2=24.56,P<0.01),前者的C/T型和T/T型频率高于后者;患者组等位基因T频率显著高于对照组(χ2=24.04,P<0.01);②阴性组、阳性组、对照组3组间基因型及等位基因分布的差异均有统计学义(χ2=37.93,P<0.01;χ2=38.90,P<0.01);两两比较显示,阴性组、阳组分别与对照组比较,基因型及等位基因分布差异均有统计学义(P<0.001).③不同基因型患者组之间PANSS各因子分和总分差异均无统计学意义(P>0.05).结论 BDNF C270T多态性与儿童精神分裂症有关,但与具体临床表现之间无明显的关系.     

TAFI基因编码区C291T的多态性与脑梗死的相关性研究

目的 探讨中国汉族人群中凝血酶激活的纤溶抑制物(TAH)基因编码区C291T的多态性与脑梗死的相关性.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测173例脑梗死患者(脑梗死组)和158例健康人(对照组)的TAFI基因编码区C291T多态性的基因型.结果 脑梗死组TAFI基因C291T多态性的CC基因型为53.2%(92/173),T等位基因携带者为46.8%(81/173);而对照组CC基因型为68.4%(108/158),T等位基因携带者为31.6%(50/158),两组之间的差异有统计学意义(χ2=7.952,P=0.005).脑梗死组C、T等位基因频率分别为70.8%(245/346),29.2%(101/346);对照组C、T等位基因频率分别为81.9%(259/316),18.1%(57/316),两组之间的差异有统计学意义(χ2=11.306,P=0.001).结论 TAFI基因编码区C291T的多态性与脑梗死呈显著性相关.     

铁调节蛋白2基因多态性与阿尔茨海默病及血管性痴呆的相关分析

目的 探讨铁调节蛋白2(IRP2)基因2616C/T多态性与阿尔茨海默病(AD)、血管性痴呆(VD)的关系.方法 用聚合酶链反应-限制性片段长度多态性技术检测281例AD、60例VD患者及285名正常老年人的IRF2基因2616C/T多念性分布,并评定简易精神状态检查表(MMSE);将AD患者按临床痴呆评定量表(CDR)评分分为轻度痴呆组(CDR=1分,72例)和中重度痴呆组(CDR=2分或3分,209例),比较各组间IRP2基因2616C/T多态性.结果 (1)AD组与对照组基因型(χ2=2.46)及等位基因(χ2=2.17)总体分布差异无统计学意义(P>0.05);而中重度AD组携带T等位基因的基因型频率(78.0%)高于对照组(69.8%;χ2=4.106,P<0.05),Logistic回归分析其中携带含T等位基因的基因型患者的比值比=1.62(95%可信区间=1.03～2.54).VD组携带含T等位基因型频率和T等位基因频率虽高于对照组,但未达统计学意义(P>0.05).(2)中重度AD患者T/T基因型频率(25.8%)和T等位基因频率(51.9%)高于轻度AD患者(分别为12.5%和40.3%),差异均有统计学意义(χ2=5.477和5.803,P<0.05).(3)携带T/T基因型的AD患者MMSE评分低于C/C基因型者(P=0.028)和C/T基因型者(P=0.014).结论 IRP2基因2616C/T多态性与中重度AD相关,而与VD可能无关联;T/T基因型可能是AD患者认知功能损害的危险因子.     

5,10-亚甲基四氢叶酸还原酶基因多态性与脑梗死患者颈动脉粥样硬化的相关性研究

目的探讨血浆同型半胱氨酸(homocysteine,Hcy)代谢酶5,10-亚甲基四氢叶酸还原酶(5,10-methylenetetrahydrofolate reductase,MTHFR)C677T基因多态性与脑梗死患者颈动脉粥样硬化的相关性。方法纳入新发前循环大动脉粥样硬化性脑梗死组患者,以无脑梗死的门诊体检者作为对照组。用荧光偏振免疫法测定两组血浆Hcy水平,彩色多普勒超声进行双侧颈动脉颅外段检查明确是否存在动脉粥样硬化斑块及斑块性质,采用全自动基因芯片检测目标人群MTHFR C677T基因型。结果共纳入新发前循环脑梗死组患者150例,对照组100例。①脑梗死组MTHFR C677T突变(TT)基因型及T等位基因频率显著高于对照组(48.0%vs 19.0%,χ~2=22.067,P0.001;64.0%vs 45.5%,χ~2=6.907,P=0.009);②脑梗死组MTHFR C677T C→T基因突变与颈动脉粥样硬化狭窄程度呈正相关(r=0.353,P0.001);③脑梗死组中不稳定斑块组MTHFR C677T突变(TT)基因型及T等位基因频率显著高于稳定斑块组(66.2%vs 34.1%,χ~2=14.587,P0.001;77.5%vs 60.2%,χ~2=6.978,P=0.008)。结论 MTHFR C677T位点C→T基因突变是颈动脉粥样硬化斑块不稳定性及其狭窄程度的相关危险因素。     

G10631A和C521T基因多态性与脑梗死相关性

目的探讨肾素-血管紧张素系统G10631A及C521T基因多态性与脑梗死患病风险的相关性。方法选择2016-05—2019-05郑州人民医院神经内科收治的100例脑梗死患者为脑梗死组,并选择同期100名健康志愿者为对照组。采集2组受试者静脉血样,采用酚/氯仿法提取DNA,采用限制性片段长度多态性分析技术检测G10631A及G521T的单核苷酸多态性。结果脑梗死组患者G10631A的AA基因型及A等位基因频率均高于对照组(χ2=8.672、10.172,P<0.05),脑梗死组患者C521T的TT基因型及T等位基因频率均高于对照组(χ2=8.665、22.118,P<0.05),G10631A的AA基因型、C521T的TT基因型可增加脑梗死发生率(OR=2.039、2.031,P<0.05)。脑梗死组患者A-T单体型出现频率高于对照组(χ2=16.127,P<0.05),但脑梗死组G-C单体型出现频率低于对照组(χ2=17.368,P<0.05)。结论肾素-血管紧张素系统G10631A的AA基因型及A等位基因、G521T的TT基因型及T等位基因和A-T单体型可能是脑梗死的遗传易感因素。     

基质金属蛋白酶-9基因多态与急性脑梗死

目的 探讨基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)基因多态及血清水平与急性脑梗死的关系.方法 对2006年1月至2007年5月期间在我院神经内科住院的急性脑梗死患者101例和我院体检中心健康体检者114名进行研究,采用ELISA法测定血清MMP-9水平,同时采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法 分析MMP-9基因启动子C-1562T多态.结果 脑梗死患者组48 h内血清MMP-9水平为(138.9±121.8)ng/ml,而对照组为(18.4±4.6)ng/ml,两组差异有统计学意义(t=9.93,P=0.00).脑梗死组CT基因型患者外周血MMP-9水平为(113.3±66.6)ng/ml.而CC基因型患者外周血MMP-9水平为(148.6±104.9)ng/ml,两者相比差异无统计学意义(t=1.22,P=0.21).脑梗死组CT+TT基因型频率13.9%,对照组为13.2%,两者比较差异无统计学意义(χ2=0.02,P=0.88),T等位基因频率在脑梗死组为6.9%,对照组为7.5%,两者比较差异也无统计学意义(χ2=0.04,P=0.83).结论 MMP-9基因启动子-1562位点的多态与MMP-9基因表达和脑梗死没有明确的关系.MMP-9基因启动子C-1562T的多态与缺血性脑血管疾病的关系有待进一步研究.     

血清基质金属蛋白酶9水平及其基因C1562T多态性与维族脑梗死患者颈动脉粥样硬化斑块稳定性的关系

目的探讨血清基质金属蛋白酶9(MMP-9)水平及其基因C1562T多态性与维族脑梗死患者颈动脉粥样硬化斑块稳定性的关系。方法采用彩色多普勒超声诊断仪对236例维族急性脑梗死患者进行颈动脉超声检测,根据颈动脉粥样硬化斑块稳定性进行分组。采用酶联免疫吸附法检测患者血清MMP-9水平,采用PCR-限制性片段长度多态性技术检测MMP-9基因C1562T的多态性。对结果进行组间比较并分析。结果颈动脉斑块呈低回声或等回声的患者有108例(易损斑块组),颈动脉斑块呈高回声的患者有128例(稳定斑块组)。易损斑块组血清MMP-9水平[(357.83±32.64)ng/ml]显著高于稳定斑块组[(304.47±38.91)ng/ml](P0.01)。两组MMP-9基因C1562T基因型CC、CT、TT的比例和等位基因C、T的频率比较,差异无统计学意义。结论血清MMP-9水平可能与维族脑梗死患者颈动脉斑块稳定性有关,而MMP-9基因C1562T多态性与维族脑梗死患者颈动脉粥样硬化斑块稳定性无关。     

Fibrous xanthomas and xanthosarcomas of the meninges and the brain

Summary Three cases of intracranial fibrous xanthomas and a case of multicentric cerebral xanthosarcoma are reported. All three fibrous xanthomas developed in the temporal area of boys in their early teens, one was within the leptomeninges (without dural attachment), the other two involved meninges and the superficial portions of the temporal lobe itself. These tumors were characterized by mono- and multinucleated cells with morphological features of histiocytes, Touton type giant cells and a storiform pattern in areas of spindleshaped tumor cells.Because of cellular atypism, giant cells and mitotic figures such tumors may suggest the diagnosis of glioblastoma multiforme but the absence of glial fibers, negative Cajal impregnation, presence of reticulin fibers in close proximity to tumor cells and the morphological similarity to the bizarre cells found in atypical xanthofibromas of the skin and soft tissues help to establish the diagnosis. Since the menigeal forms are probably derived from local meningeal mesenchyme, occasional abortive whorls and pseudopsammoma bodies may be encountered, the overall picture, however, is very different from meningiomas. Two patients had a 2.5 and a 12 year long symptomfree survival, respectively. The third boy had a local recurrence 14 months after initial removal which was excised and the patient is presently doing well.The xanthosarcoma first developed in the right frontal lobe of a 26 year old woman. This tumor was almost exclusively made up of various sized anaplastic cells filled with birefringent lipids. It is suggested that this tumor which had a diffuse network of reticulin, had originated from primitive adventitial cells. It was histologically more malignant than the first three and the patient died within a year after removal of the frontal lobe tumor, from a second mass in the cerebellum. The relationship of this tumor to glioblastomas and to other types of giant cell sarcomas is discussed.This paper was presented in part at the 6th International Congress of Neuropathology in Paris, France, on August 31, 1970.     

Investigating the construct validity of the SPAI-C: comparing the sensitivity and specificity of the SPAI-C and the SAS-A

Investigates the construct validity of the Social Phobia and Anxiety Inventory for Children (SPAI-C) by comparing its sensitivity and specificity with another self-report measure of social anxiety, the Social Anxiety Scale for Adolescents (SAS-A). Participants were 252 adolescents (124 males and 128 females) 13-17 years old. Adolescents completed the SPAI-C and the SAS-A and were interviewed using the Anxiety Disorders Interview Schedule for DSM-IV: Child Version (ADIS-IV:C). Parents were also interviewed and composite diagnoses were formed. Youth were classified as socially phobic or non-anxious based on these composite diagnoses. By comparing clinical cutoff scores with diagnostic group classification, the sensitivity and the specificity of the SPAI-C and SAS-A were compared. Results indicated that the SPAI-C was a more sensitive measure than the SAS-A (61.5% vs. 43.6%) providing evidence of the scale's construct validity. The two measures were similar with regard to specificity (82.7% for both). Implications of these results for assessment and research are discussed.     

Alzheimer's disease and the pivotal role of the hypothalamus and the intrinsic opioid system

Although the "cholinergic hypothesis" of the pathophysiology of Alzheimer's disease has received great attention during the past years, it has recently come under increasing criticism specifically owing to failure of therapeutic endeavors based on this premise. As the potential broad role of the intrinsic opioids in the neurochemical modulation of diverse brain functions emerges, the realization that these data may be reconciled to a unifying hypothesis underlying the nature of some chronic dementing diseases (including Alzheimer's disease, Korsakoff disease and Parkinson's disease) occurs. Certain specific characteristics of the known pathologic changes and neurotransmitter deficits of Alzheimer's disease may be explained based on an early vulnerability of the hypothalamus combined with derangements of endorphinergic functions which follow. The latter may be implicated in the subsequent degeneration of structures receiving projections from the arcuate nucleus of the hypothalamus. This is based on the known role of endorphins in the modulation of central neurotransmitters and specifically acetylcholine activity. In addition, the reciprocal neuroendocrine and neuroimmunologic interactions mediated through the hypothalamus, may be of further importance in the evolution of Alzheimer's disease.