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121.
122.
David A Grimes J David Grimes Lem Racacho Kylie A Scoggan Fabin Han Betty Anne Schwarz John Woulfe Dennise Bulman 《Movement disorders》2002,17(6):1205-1212
The identification of rare, large families with Parkinson's disease (PD) has provided important clues that have contributed to our understanding of this complex disorder. We have identified a large French-Canadian kindred that spans five generations consisting of more than 90 individuals. A total of 65 individuals now have been examined, had venous blood drawn, and DNA extracted. Two-point and multipoint linkage analysis was performed to assess linkage to known PD genes or loci. Within the third and fourth generations of this family there are 10 living, plus 3 deceased members with well-documented levodopa responsive parkinsonism. Autopsy results on 1 member demonstrated the loss of pigmented neurons in the substantia nigra and the presence of alpha-synuclein positive Lewy bodies. Four of the PD patients have prominent postural and kinetic tremors that preceded their parkinsonism by up to 10 years. Two other individuals within the family have prominent isolated postural and kinetic tremors without parkinsonism. The alpha-synuclein(4q21.3-23), Parkin(6q25.2-27), PARK3 (2p13), PARK4, and ubiquitin carboxy terminal hydrolase-L1 (4p14-16.3) and PARK6 and PARK7 (1p35-36) loci were excluded in this kindred using closely linked markers. The clinical and pathological features of this family are consistent with the diagnosis of PD. This family further demonstrates the known genetic heterogeneity in PD and is large enough that a genome-wide screen has been undertaken in an effort to identify a novel PD gene. 相似文献
123.
Magnus Stangenberg Gran Lingman George Roberts Pinar Ozand 《American journal of medical genetics. Part A》1992,44(2):142-144
We report on fetal hydrops presenting at 18 weeks of gestation and diagnosed as β-glucuronidase deficiency. The parents were first cousins and there were 2 previous similar fetal deaths. β-Glucuronidase was absent in cultured fetal fibroblasts and lymphoblasts but was normal in the tested relatives. The activities of other lysosomal enzymes were normal. © 1992 Wiley-Liss, Inc. 相似文献
124.
The presence and binding properties of epidermal growth-factor receptors (EGF-Rs) in different cell types purified from the rat medial septal area in culture were investigated. We report that astrocytes, oligodendrocytes and neurons from this area possess EGF-Rs while microglia do not. EGF-binding sites are detectable on astrocytes derived from the medial septum of both embryonic and neonatal rats. Scatchard analysis of the data for astrocytes from the fetal rats show that EGF specifically binds to both high- (Kd = 7.21 × 10−10 M, Bmax = 3602 receptors/cell) and low-affinity (Kd = 3.99 × 10−8 10−8 M, Bmax = 6,265 receptors/cell) receptors on these cells. On the other hand, astrocytes purified from neonatal tissue possess a greater number of high-affinity receptors (Bmax = 10,938 receptors/cell) when compared with the embryonic astroglia. With time in culture, the number of both types of receptors on neonatal astrocytes decreases. Oligodendrocytes also possess high- and low-affinity EGF-Rs with dissociation constants of 3.25 × 10−10 M and 3.85 × 10−8 M, respectively. The number of receptors on oligodendrocytes is significantly lower than those on neonatal astrocytes (Bmax = 1185 and 25,081 receptors/cell for high- and low-affinity binding sites, respectively). Finally, neurons from this area also exhibit two different EGF-R types with dissociation constants similar to those described for astrocytes. As the number of receptors/neuron (Bmax = 136 and 1159 receptors/cell for high- and low-affinity binding sites, respectively) appears to be extremely low, it is possible that EGF specifically binds only to a subpopulation of neurons from this area. These studies demonstrate which cell types in the developing medial sepal area posses EGF-Rs and provide a detailed characterization of these binding sites. These EGF-R-bearing cells may be potential targets for this growth factor or for transforming growth factor α in this brain area. 相似文献
125.
Lorraine D. Buckberry Ian S. Blagbrough Barrie W. Bycroft P.Nicholas Shaw 《Toxicology letters》1992,60(3):241-246
The C-S lyase enzymes are responsible for the generation of mutagenic and cytotoxic metabolites via aberrant drug-metabolising pathways in mammalian tissues. We have examined human hepatic cytosolic, mitochondrial and microsomal fractions for evidence of C-S lyase activity. The cytosolic enzyme was purified using fast protein liquid chromatography over FFQ Sepharose, Mono P and Superose 12. An homogeneous protein (monitored by SDS-PAGE) was obtained following purification, and an 11-fold increase in C-S lyase specific activity was observed. The molecular weight of the enzyme was found to be 37 kDa in denaturing conditions, 82.3 kDa in non-denaturing conditions, and the C-S lyase activity was shown to co-purify with kynurenine aminotransferase activity when the transaminase activity of the enzyme was examined with kynurenine as the substrate. 相似文献
126.
Dopamine transporter density is decreased in parkinsonian patients with a history of manganese exposure: What does it mean? 总被引:2,自引:0,他引:2
Y Kim J-M Kim J-W Kim C-I Yoo C R Lee J H Lee H K Kim S O Yang H K Chung D S Lee B Jeon 《Movement disorders》2002,17(3):568-575
Manganese (Mn) exposure can cause parkinsonism. Pathological changes occur mostly in the pallidum and striatum. Two patients with a long history of occupational Mn exposure presented with Mn-induced parkinsonism. In one patient, magnetic resonance imaging (MRI) showed findings consistent with Mn exposure, and Mn concentration was increased in the blood and urine. However, this patient's clinical features were typical of idiopathic Parkinson disease (PD). Previous pathological and positron emission tomography studies indicate that striatal dopamine transporter density is normal in Mn-induced parkinsonism, whereas it is decreased in PD. Therefore, we performed [(123)I]-(1r)-2 beta-carboxymethoxy-3beta-(4-iodophenyl)tropane ([(123)I]-beta-CIT) single-photon emission computed tomography. Severe reduction of striatal beta-CIT binding was indicated, which is consistent with PD. We propose three interpretations: (1) the patients have PD, and Mn exposure is incidental; (2) Mn induces selective degeneration of presynaptic dopaminergic nerve terminals, thereby causing parkinsonism; or (3) Mn exposure acts as a risk of PD in these patients. Our results and careful review of previous studies indicate that the axiom that Mn causes parkinsonism by pallidal lesion may be over-simplified; Mn exposure and parkinsonism may be more complex than previously thought. Further studies are required to elucidate the relationship between Mn and various forms of parkinsonism. 相似文献
127.
To elucidate the pathogenesis of angioimmunoblastic lymphadenopathy-like T cell lymphoma (AILD-T) we investigated the T cell receptor Vβ gene repertoires of four AILD-Ts and compared them with those of other histological types of lymphomas and three cases with reactive disorders. All lymphoma patients had rearrangement bands detected by Southern blot analysis. Only 1 of the 4 cases of AILD-T showed a single predominant usage of Vβ 20 gene by PCR with 20 different Vβ specific primers and the others had repertoires somewhat restricted but similar to reactive lesions. Subsequent sequencing of this PCR product revealed that only 2 of 7 clones were identical. These results suggest the monoclonal malignant cells in AILD-T are scant and that the infiltrating T cells show a reactive pattern. In the only AILD-T case with a single dominant Vβ usage, the relationships of this repertoire and lymphoma cells seems to be of some consequence. 相似文献
128.
Circling behavior in honey bees 总被引:1,自引:0,他引:1
Unilateral microinjections of gamma-aminobutyric acid (GABA), acetylcholine (ACh) and related substances into central parts of the brain of the honey bee elicit a quantifiable circling behavior. GABA (40 nl, 10(-2) M, muscimol (40 nl, 10(-4) M) and flaxedil (10(-3) M, 40 nl) induce contralateral circling whilst ACh (40 nl, 10(-2) M), nicotine (40 nl, 10(-4) M) and picrotoxin (40 nl, 10(-3) M) induce ipsilateral circling if injected in the proximity of the alpha-lobe (50-100 microns) of the of the mushroom body. Mechanical lesions of the pedunculus induce ipsilateral circling. This can be reversed by ipsilateral injections of GABA and flaxedil. Intracellular recordings demonstrate a hyperpolarizing effect of GABA and a depolarising effect of ACh on individual neurons in this region. These results suggest that circling behavior in the bee is controlled by the balance of GABA in the alpha-lobes and mediated by acetylcholinergic neurons. 相似文献
129.
目的探讨细胞色素b(cytochrome b,Cytb)与高氧肺损伤发生、发展的关系。方法早产新生SD(Sprague-Dawley)大鼠生后1d随机分为空气组、高氧组,高氧组持续暴露于常压氧舱中,氧浓度〉85%;空气组置于同一室常压空气中。两组分别于高氧或空气暴露后1、4、7、10和14d时提取肺组织RNA,采用半定量逆转录聚合酶链反应(RT-PCR)测定CytbmRNA表达;同时应用免疫组化方法检测肺组织切片中Cytb蛋白表达;应用Western-blot检测高氧肺损伤肺组织中Cytb蛋白水平的表达变化。结果与空气组相比,高氧暴露1d、4d CytbmRNA含量及其表达显著增强(P〈0.05);7d后Cytb呈下降趋势,其表达较空气组减弱,但两者相比差异无统计学意义(P〉0.05)。高氧暴露后,随日龄变化肺组织Cytb免化结果与CytbmRNA表达相似;与空气组相比,高氧暴露1d、4d肺组织Cytb表达显著增强(P〈0.05);7d后Cytb呈逐渐下降趋势,其表达较空气组减弱,但7、10d两组相比差异无统计学意义,14d极显著减弱(P〈0.01)。Western-blot实验结果:与空气组相比,高氧暴露1d、4dCytb蛋白水平表达增强但两组相比差异无统计学意义(P〉0.05);7d后Cytb呈下降趋势,其表达较空气组减弱,但7、10d两组相比差异无统计学意义(P〉0.05),而14d显著减弱(P〈0.05)。结论85%高浓度氧暴露诱导早产新生大鼠线粒体编码的Cytb异常表达,这种变化可能参与高氧肺损伤的发生。 相似文献
130.
P16MTS1、P27KIP1基因在胆管癌组织中的表达研究 总被引:2,自引:0,他引:2
目的:探讨P16^MIS1,P27^KIP1基因与胆管癌临床病理的关系。方法:采用免疫组化方法,检测48例胆管癌和8例伴慢性炎症的胆管壁组织中P16^MIS1,P27^KIP1蛋白表达情况。结果:(1)胆管癌中P16^MIS1,P27^KIP1阳性表达率分别为47.9%和35.4%,而伴炎症的胆管组织阳性表达率为100%和87.5%;(2)P16^MIS1,P27KIP1蛋白表达与胆管癌的分化程度,有无淋巴结或远处转移以及临床分期呈显著相关性。结论:P16^MIS1,P27^KIP1多基因表达异常可能与胆管癌的发生发展有关,是衡量胆管癌预后的有用指标。 相似文献