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Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulfatase A. This leads to the accumulation of 3-O-sulfogalactosylceramide, which results in severe demyelination. Here we describe a novel non-sense mutation W124ter and two disease-causing missense mutations E382Q and C500F in arylsulfatase A gene. Another so far unknown allele harbors three sequence alterations: two polymorphisms (N350S, R496H) and a missense mutation (R288H). The R288H substitution and the N350S polymorphism have previously been found on one allele together with a polymorphism in a polyadenylation signal characteristic for the arylsulfatase A pseudodeficiency allele. The R496H has been shown to occur on another allele. The presence of the R288H, N350S, and R496H substitution on one allele in the absence of the polyadenylation site polymorphism shows that this allele has probably arisen by recombination between the nucleotides of codon 350 and 496. 相似文献
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Almasirad A Tabatabai SA Faizi M Kebriaeezadeh A Mehrabi N Dalvandi A Shafiee A 《Bioorganic & medicinal chemistry letters》2004,14(24):191-6059
A series of new 2-substituted-5-[2-(2-fluorophenoxy)phenyl]-1,3,4-oxadiazoles has been synthesized and screened for their anticonvulsant activities. Compound 3 shows considerable anticonvulsant activity both in PTZ and MES models. It seems that this effect is mediated by benzodiazepine receptors and other unknown mechanism, respectively. 相似文献
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The purpose of this study was to evaluate the nature of film formation on tablets with different compositions, using confocal
laser scanning microscopy (CLSM), and to measure film adhesion via the application of a novel “magnet probe test”. Three excipients,
microcrystalline cellulose (MCC), spray-dried lactose monohydrate, and dibasic calcium phosphate dihydrate, were individually
blended with 0.5% magnesium stearate, as a lubricant, and 2.5% tetracycline HCl, as a fluorescent marker, and were compressed
using a Carver press. Tablets were coated with a solution consisting of 7% hydroxypropyl methylcellulose (HPMC) phthalate
(HP-55), and 0.5% cetyl alcohl in acetone and isopropanol (11:9). The nature of polymer interaction with the tablets and coating
was evaluated using CLSM and a designed magnet probe test. CLSM images clearly showed coating efficiency, thickness, and uniformity
of film formation, and the extent of drug migration into the film at the coating interfaces of tablets. Among the excipients,
MCC demonstrated the best interface for both film formation and uniformity in thickness relative to lactose monohydrate and
dibasic calcium phosphate dihydrate. The detachment force of the coating layers from the tablet surfaces, as measured with
the developed magnet probe test, was in the order of MCC>lactose monohydrate>dibasic calcium phosphate dihydrate. It was also
shown that the designed magnet probe test provides reliable and reproducible results when used for measurement of film adhesion
and bonding strength. 相似文献
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Shane Deegan Svetlana Saveljeva Sanjeev Gupta David C MacDonald Afshin Samali 《Biochemical and biophysical research communications》2014
Cells respond to endoplasmic reticulum (ER) stress through the unfolded protein response (UPR), autophagy and cell death. In this study we utilized casp9+/+ and casp9−/− MEFs to determine the effect of inhibition of mitochondrial apoptosis pathway on ER stress-induced-cell death, UPR and autophagy. We observed prolonged activation of UPR and autophagy in casp9−/− cells as compared with casp9+/+ MEFs, which displayed transient activation of both pathways. Furthermore we showed that while casp9−/− MEFs were resistant to ER stress, prolonged exposure led to the activation of a non-canonical, caspase-mediated mode of cell death. 相似文献
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Sedaghati T Yang SY Mosahebi A Alavijeh MS Seifalian AM 《Biotechnology and applied biochemistry》2011,58(5):288-300
Repairing nerve defects with large gaps remains one of the most operative challenges for surgeons. Incomplete recovery from peripheral nerve injuries can produce a diversity of negative outcomes, including numbness, impairment of sensory or motor function, possibility of developing chronic pain, and devastating permanent disability. In the last few years, numerous microsurgical techniques, such as coaptation, nerve autograft, and different biological or polymeric nerve conduits, have been developed to reconstruct a long segment of damaged peripheral nerve. A few of these techniques are promising and have become popular among surgeons. Advancements in the field of tissue engineering have led to development of synthetic nerve conduits as an alternative for the nerve autograft technique, which is the current practice to bridge nerve defects with gaps larger than 30 mm. However, to date, despite significant progress in this field, no material has been found to be an ideal alternative to the nerve autograft. This article briefly reviews major up-to-date published studies using different materials as an alternative to the nerve autograft to bridge peripheral nerve gaps in an attempt to assess their ability to support and enhance nerve regeneration and their prospective drawbacks, and also highlights the promising hope for nerve regeneration with the next generation of nerve conduits, which has been significantly enhanced with the tissue engineering approach, especially with the aid of nanotechnology in development of the three-dimensional scaffold. The goal is to determine potential alternatives for nerve regeneration and repair that are simply and directly applicable in clinical conditions. 相似文献
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Don't lose heart--therapeutic value of apoptosis prevention in the treatment of cardiovascular disease 总被引:4,自引:0,他引:4
Cardiovascular disease is a leading cause of death worldwide. Loss of function or death of cardiomyocytes is a major contributing factor to these diseases. Cell death in conditions such as heart failure and myocardial infarction is associated with apoptosis. Apoptotic pathways have been well studied in non-myocytes and it is thought that similar pathways exist in cardiomyocytes. These pathways include death initiated by ligation of membrane-bound death receptors, release of pro-apoptotic factors from mitochondria or stress at the endoplasmic reticulum. The key regulators of apoptosis include inhibitors of caspases (IAPs), the Bcl-2 family of proteins, growth factors, stress proteins, calcium and oxidants. The highly organized and predictive nature of apoptotic signaling means it is amenable to manipulation. A thorough understanding of the apoptotic process would facilitate intervention at the most suitable points, alleviating myocardium decline and dysfunction. This review summarizes the mechanisms underlying apoptosis and the mediators/regulators involved in these signaling pathways. We also discuss how the potential therapeutic value of these molecules could be harnessed. 相似文献
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Alterations in the p53 tumor suppressor gene are important events in many cases of human cancers. We have developed a novel microarray based approach for re-sequencing and mutation detection of the p53 gene. The method facilitates rapid and simple scanning of the target gene sequence and could be expanded to include other candidate cancer genes. The methodology employs the previously described apyrase-mediated allele-specific extension reaction (AMASE). In order to re-sequence the selected region, four extension oligonucleotides with different 3'-termini were used for each base position and they were covalently attached to the glass slide's surface. The amplified single-stranded DNA templates were then hybridized to the array followed by in situ extension with fluorescently labeled dNTPs in the presence of apyrase. The model system used was based on analysis of a 15 bp stretch in exon 5 of the p53 gene. Mutations were scored as allelic fractions calculated as (wt)/(wt + mut) signals. When apyrase was included in the extension reactions of wild type templates, the mean allelic fraction was 0.96. When apyrase was excluded with the same wild type templates, significantly lower allelic fractions were obtained. Two 60-mer synthetic oligonucleotides were used to establish the detectable amount of mutations with AMASE and a clear distinction between all the points could be made. Several samples from different stages of skin malignancies were also analyzed. The results from this study imply the possibility to efficiently and accurately re-sequence the entire p53 gene with AMASE technology. 相似文献
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