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71.
Dystonia is a common movement disorder which is thought to represent a disease of the basal ganglia. However, the pathogenesis of the idiopathic dystonias, i.e. the neuroanatomic and neurochemical basis, is still a mystery. Research in dystonia is complicated by the existence of various phenotypic and genotypic subtypes of idiopathic dystonia, probably related to heterogeneous dysfunctions.In neurological diseases in which no obvious neuronal degeneration can be found, such as in idiopathic dystonia, the identification of a primary defect is difficult, because of the large number of chemically distinct, but functionally interrelated, neurotransmitter systems in the brain.The variable response to pharmacological agents in patients with idiopathic dystonia supports the notion that the underlying biochemical dysfunctions vary in the subtypes of idiopathic dystonia. Hence, in basic research it is important to clearly define the involved type of dystonia.Animal models of dystonias were described as limited. However, over the last years, there has been considerable progress in the evaluation of animal models for different types of dystonia.Apart from animal models of symptomatic dystonia, genetic animal models with inherited dystonia which occurs in the absence of pathomorphological alterations in brain and spinal cord are described.This review will focus mainly on genetic animal models of different idiopathic dystonias and pathophysiological findings. In particular, in the case of the mutant dystonic (dt) rat, a model of generalized dystonia, and in the case of the genetically dystonic hamster (dtsz), a model of paroxysmal dystonic choreoathetosis has been used, as these show great promise in contributing to the identification of underlying mechanisms in idiopathic dystonias, although even a proper animal model will probably never be equivalent to a human disease.Several pathophysiological findings from animal models are in line with clinical observations in dystonic patients, indicating abnormalities not only in the basal ganglia and thalamic nuclei, but also in the cerebellum and brainstem. Through clinical studies and neurochemical data several similarities were found in the genetic animal models, although the current data indicates different defects in dystonic animals which is consistent with the notion that dystonia is a heterogenous disorder.Different supraspinal dysfunctions appear to lead to manifestation of dystonic movements and postures. In addition to increasing our understanding of the pathophysiology of idiopathic dystonia, animal models may help to improve therapeutic strategies for this movement disorder. 相似文献
72.
目的:探讨GPC4基因与中国山东Smith-Fineman-Myers综合征(SFMS)的关系,并分析SFMS患者GPC4基因突变。方法:利用primer3设计扩增GPC4全部编码序列及内含子和外显子接头序列的引物,采用PCR扩增结合PCR产物直接测序方法检测GPC4基因开放性阅读框架区域基因突变。结果:在GPC4基因开放性阅读框架区域内并未检测到导致疾病的基因突变。结论:山东SFMS家系患者不是由于GPC4基因编码区域基因突变所致。 相似文献
73.
L. Portengen G. de Meer G. Doekes D. Heederik 《Clinical and experimental allergy》2004,34(8):1243-1250
BACKGROUND AND OBJECTIVES: We have previously reported that high rat urinary allergen (RUA) exposure was not associated with increased risk of rat allergy in long-term-exposed laboratory animal (LA) workers. We aimed to assess whether strong allergen-specific IgG4 responses could explain the absence of a dose response in these subjects. We investigated whether IgG4 was associated with allergen exposure and prevalence of sensitization or respiratory symptoms to rats. The longitudinal relation between IgG4 and rat allergy was studied using data obtained during 2 years of follow-up. METHODS: Five hundred and twenty-nine LA workers answered a questionnaire on respiratory symptoms and occupational history and participated in skin prick testing. Blood samples were analysed for specific IgG4 and IgE to RUA. Exposure to RUA was estimated based on personal air samples. The relation between IgG4 and newly occurring sensitization or rat allergy was studied in workers who were not sensitized or did not report respiratory symptoms to rats. RESULTS: IgG4 titres were higher in atopic than in non-atopic subjects, and increased with higher allergen exposure. Titres were highest in subjects who were sensitized and reported respiratory symptoms to rats when compared with those who were not (geometric mean [geometric standard deviation] = 202 [5.7] vs. 8.4 [18.3] AU). The association between IgG4 and sensitization or symptomatic rat allergy was independent of estimated allergen exposure. IgG4 was a strong predictor of newly occurring sensitization and symptomatic rat allergy during follow-up in atopic and rat-sensitized subjects. CONCLUSION: High exposure to RUA is associated with a strong allergen-specific IgG4 antibody response. High anti-RUA IgG4 is a strong predictor of prevalent and incident sensitization and symptomatic rat allergy in atopic and rat-sensitized subjects. IgG4 can therefore not explain the absence of a dose response between allergen exposure and allergy in long-term-exposed workers. We consider anti-RUA IgG4 to be a marker that combines aspects of exposure and susceptibility. 相似文献
74.
75.
C4d Deposition and Clearance in Cardiac Transplants Correlates With Alloantibody Levels and Rejection in Rats 总被引:4,自引:3,他引:1
K. Minami K. Murata C.-Y. Lee K. Fox-Talbot B. A. Wasowska M. D. Pescovitz W. M. Baldwin III 《American journal of transplantation》2006,6(5P1):923-932
Antibody-mediated rejection of human cardiac transplants is correlated with C4d deposits and macrophage infiltrates in capillaries of endomyocardial biopsies. We produced an antibody to rat C4d to study C4d deposition and clearance in Lewis rats that were sensitized with a blood transfusion from DA rats 7, 14 or 21 days before cardiac transplantation. Cyclosporin A (CsA) immunosuppression was initiated after transplantation at a dose that inhibited graft rejection, antibody production and C4d deposition in unsensitized recipients. Blood transfusion elicited high levels of circulating IgG alloantibodies, predominantly of the complement-activating IgG2b subclass, that peaked 14 days after transplantation. At this time, macrophages accumulated in capillaries, and C4d deposits were diffuse and intense on arteries, capillaries and veins. Grafts that survived 90 days in sensitized recipients still had deposits of C4d that were associated with increased interstitial fibrosis and vasculopathy in arteries. Clearance of C4d was determined by retransplanting DA cardiac allografts from Lewis recipients back to DA recipients. C4d deposits were decreased to minimal levels within 5 days after retransplantation. Thus, C4d deposition is not limited to the capillaries, but extends throughout the arterial tree, and despite formation of a covalent bond, C4d is cleared within days. 相似文献
76.
M. Depré D. J. Margolskee A. Van Hecken J. S. Y. Hsieh A. Buntinx P. J. De Schepper J. D. Rogers 《European journal of clinical pharmacology》1992,43(4):431-433
Summary The disposition of the enantiomers of MK-571 (MK-0679 and L-668,018) following single i. v. doses of MK-571 (L-660,711) was studied in a three way cross-over study in 12 healthy male volunteers. Each volunteer received 75 mg, 300 mg and 600 mg i. v. doses of MK-571 at weekly intervals.The disposition of both enantiomers appeared dose-dependent, since the AUC increased disproportionately faster than the dose. The dose dependency was much more pronounced for L-668,018: its AUC increased 6-fold from the 75 to the 300 mg dose, 16-fold from 75 to 600 mg and 2.7 fold from 300 to 600 mg. For MK-0679, the corresponding increases in AUC were 4.8-, ll-, and 2.3 fold. Regardless of dose, the elimination of L-668,018 was more rapid than that of MK-0679.The disposition of MK-0679 needs to be investigated independently to detect any potential influence of L-668,018 on its disposition. 相似文献
77.
本文对19例中药雷公藤服用者精子、精浆中乳酸脱氢酶(LDH)及同功酶C_4(LDHC_4)的活性进行了测定分析。发现服药后以单位数量精子表示的LDHC_4活性在精子、精浆中均有明显升高(双侧非参数秩和检验,分别为P<0.01和P<0.02);通过酶活性与精子计数的相关分析,显示服药后精浆LDHC_4活性(mU/ml)与精子计数的正相关性(r=0.2279)较服药前(r=0.5505)弱,可能与精液中精子以外的其他LDHC_4来源贡献增大有关,诸如生精细胞的分解增多等。本文认为服药后精子LDHC_4活性上升,精液中非成熟精子比例增高是其原因之一。 相似文献
78.
中国人不同C4基因型时血中C4浓度的定量检测 总被引:1,自引:0,他引:1
用神经氨酸酶及羧肽酶B处理血浆,依次经C4高压琼脂糖电泳、免疫固定、薄层激光扫描等步骤,并结合血浆免疫火箭电泳定量法对我国武汉地区随机人群的血浆C4总量及C4两种同种型,主要别型,单、双QO,重复座位等时的血浆C4含量进行了检测与分析。结果发现:遗传因素明显影响血浆C4水平,因而在群体中表现宽广的C4浓度范围,特别在有C4QO与C4重复基因座位时差异特别明显。这一研究提示,不同的C4基因型,循环C4含量表现明显差异。临床上检测C4含量时应该考虑患者的C4基因型别。 相似文献
79.
D. A. Basketter E. W. Scholes M. Cumberbatch C. D. Evans I. Kimber 《Contact dermatitis》1992,27(4):209-213
The guinea pig maximization test (GPMT) has proven to be a valuable tool for the identification of the skin sensitization potential of chemicals. The method identifies a hazard which can lead in the EC to compulsory labelling of that chemical. In the present study, data on sulphanilic acid derived from the GPMT has been compared with results from a second guinea pig assay (the cumulative contact enhancement test) and the murine local lymph node assay, both of which require only topical application of chemical. Except for the GPMT, no test identified any sensitizing activity associated with exposure to sulphanilic acid. These latter results are consistent with the experience gained from substantial human exposure in an occupational setting and from which no cases of allergic contact dermatitis to sulphanilic acid have arisen over a 20-year period. In consequence, it is questioned which test protocol in practice has given the more accurate identification of sensitization hazard relevant to man. 相似文献
80.
Ko-Huang Lue Yung-Hsiang Lin Hai-Lun Sun Ko-Hsiu Lu Jie-Cheng Hsieh Ming-Chih Chou 《Pediatric allergy and immunology》2006,17(6):408-415
Immunotherapy through oral routes is thought to be a valuable therapeutic option for asthma. The clinical and immunologic effects of sublingual immunotherapy (SLIT) in children with asthma caused by mites were evaluated in a double-blind, placebo-controlled study for 6 months. Patients (aged 6-12 yr) with mild-to-moderate asthma, with single sensitization to mite allergen, received either SLIT or placebo with a standardized Dermatophagoides pteronyssinus (D.p.)/D. farinae (D.f.) 50/50 extract. The cumulative dose was around 41824 IR, equivalent to 1.7 mg of D.p. and 3.0 mg of D.f. allergen. Symptom and medication scores were assessed throughout the study. Serum total immunoglobulin (Ig)E, eosinophil count, eosinophil cationic protein, specific IgE, specific IgG4, and skin sensitivity were evaluated before starting the treatment and after the treatment period. Twenty patients completed the study. At the beginning of the treatment, no differences were observed between the groups for symptom and medication scores, skin sensitivity, or immunologic parameters. After 6 months of treatment, there was a significant difference in nighttime asthma symptom scores and specific IgG4 (p < 0.05) in the SLIT group compared with the placebo group. Daytime symptom and medication scores, total IgE, eosinophil count, forced expiratory volume in 1 s, and mean evening peak expiratory flow rate reached significant differences in the SLIT group during the treatment period (p < 0.05). No severe adverse effects were reported. Our results revealed that treatment for 6 months with SLIT is clinically effective in decreasing asthmatic symptoms and medication use in children with mild-to-moderate asthma because of mite sensitivity. The clinical usefulness of this form of immunotherapy and the mechanism underlying its immunologic effects deserve further studies. 相似文献