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101.
Zellweger syndrome is a peroxisomal biogenesis disorder that results in abnormal neuronal migration in the central nervous system and severe neurologic dysfunction. The pathogenesis of the multiple severe anomalies associated with the disorders of peroxisome biogenesis remains unknown. To study the relationship between lack of peroxisomal function and organ dysfunction, the PEX2 peroxisome assembly gene (formerly peroxisome assembly factor-1) was disrupted by gene targeting. Homozygous PEX2-deficient mice survive in utero but die several hours after birth. The mutant animals do not feed and are hypoactive and markedly hypotonic. The PEX2-deficient mice lack normal peroxisomes but do assemble empty peroxisome membrane ghosts. They display abnormal peroxisomal biochemical parameters, including accumulations of very long chain fatty acids in plasma and deficient erythrocyte plasmalogens. Abnormal lipid storage is evident in the adrenal cortex, with characteristic lamellar-lipid inclusions. In the central nervous system of newborn mutant mice there is disordered lamination in the cerebral cortex and an increased cell density in the underlying white matter, indicating an abnormality of neuronal migration. These findings demonstrate that mice with a PEX2 gene deletion have a peroxisomal disorder and provide an important model to study the role of peroxisomal function in the pathogenesis of this human disease. 相似文献
102.
LD Rodger GP Carlson ME Moran TB Yarbrough JR Pascoe JA Reynolds 《Canadian Metallurgical Quarterly》1995,9(4):280-282
A 3-year-old Thoroughbred colt was presented for evaluation of azotemia and anorexia. Physical examination revealed a ureterolith in the left ureter, approximately 10 cm from the bladder, which was thought to obstruct urine flow by approximately 90% when viewed cystoscopically. Ultrasonographic examination of both kidneys revealed indistinct corticomedullary junctions, and the right kidney was more hyperechoic. A percutaneous biopsy of the right kidney revealed chronic interstitial nephritis with marked interstitial medullary fibrosis. Medical therapy consisting of IV fluids, sodium chloride PO, and ammonium chloride PO was initiated. Ureteroscopic electrohydraulic lithotripsy via a perineal urethrostomy was used to successfully remove the stone. Klebsiella oxytoca, which responded to oral enrofloxacin therapy, was cultured from the urine after surgery. Azotemia resolved and the horse resumed training. 相似文献
103.
ME Reilly D Mantle PJ Richardson J Salisbury J Jones TJ Peters VR Preedy 《Canadian Metallurgical Quarterly》1997,21(5):792-798
The complexity of the spot patterns of two-dimensional electrophoresis gels made it necessary to use image processing techniques to analyze the gels. An important issue in the analysis is the detection and quantification of the protein spots. In this paper we describe a new technique to segment and model the different spots. For the segmentation of a gel into its different spot regions we apply a watershed technique, which is robust and efficient. For the quantification of the spots, a new spot model is constructed, based on diffusion principles. Besides the advantage of having a physical interpretation, the model is demonstrated to be superior to the commonly used Gaussian models. 相似文献
104.
The level of care for children over the past 5 years has become bimodal, with most children with low levels of dental caries having good maintenance care, but those with moderate to high caries receiving significantly poorer care. Capitation has led to supervised neglect for many children who develop dental decay. This is not at all unexpected considering the general lack of concern by the government and public dental services and the fact that the level of payment of GDPs is such that they cannot afford to treat children. The problems of the dental care of children in the UK are compounded by the lack of specialist paediatric dentists for the more difficult patient. 相似文献
105.
106.
Unlike inhaled beta 2-agonists, more studies need to be performed before the action of systemic beta 2-agonists on athletic performance can be assessed accurately. Experiments in animals with oral clenbuterol have shown augmentation in muscle bulk across numerous species, but human studies cannot confirm similar muscle mass enlargement in healthy men. Although the human studies demonstrate the potential for long-acting systemic beta 2-agonists to increase muscle strength in certain muscle fiber types, it is difficult to judge the drugs' effects on overall athletic performance, because athletic skill is more than strength, speed, and endurance. The effect of oral clenbuterol on athletic performance cannot be evaluated from its actions on muscle strength alone. However, as evidence stands now, sports regulatory agencies are correct to ban systemic beta 2-agonists until the following 2 points can be proven: (1) oral forms provide a therapeutic benefit that cannot be obtained with aerosol or inhaled forms; and (2) oral forms do not give any unfair advantage to the competitor in muscle strength, power output, or endurance. Provided they are administered as prescribed, aerosol or inhaled beta-agonists do not impart an unfair advantage or enhance athletic performance and can continue to be used in competition by athletes with EIA. 相似文献
107.
Fuller's Earth, a dioctahedral calcium montmorillonite clay mineral of the smectite group, undergoes thermal transformation via a series of complex intermediate states that are highly structurally disordered. Fuller's Earth is a commercially significant material with considerable levels of paramagnetic iron (Fe3+) substitution into octahedrally coordinated metal sites. Despite the high iron-content (approximately 10% of the occupied octahedral metal sites) in these samples 29Si and 27Al magic angle spinning (MAS) NMR spectra of sufficient quality are obtained to reveal structural changes in samples that have been heated from room temperature to 1400 degrees C. Two major structural changes are clearly observed, initial dehydroxylation and then collapse of the layer structure into more highly connected silica-rich domains and an alumina-rich phase. 相似文献
108.
MJ Lemmon P van Zijl ME Fox ML Mauchline AJ Giaccia NP Minton JM Brown 《Canadian Metallurgical Quarterly》1997,4(8):791-796
A fundamental obstacle in gene therapy for cancer treatment is the specific delivery of an anticancer gene product to a solid tumor. Although several strategies exist to control gene expression once a vector is directly introduced into a tumor, as yet no systemic delivery system exists that specifically targets solid tumors. Nonpathogenic, obligate anaerobic bacteria of the genus Clostridium have been used experimentally as anticancer agents because of their selective growth in the hypoxic regions of solid tumors after systemic application. In this report we further describe a novel approach to cancer gene therapy in which genetically engineered clostridia are used as tumor-specific vectors for the delivery of antitumor genes. We have introduced into a strain of C. beijerinckii the gene for an E. coli nitroreductase known to activate the nontoxic prodrug CB 1954 to a toxic anticancer drug. Nitroreductase produced by these clostridia enhanced the killing of tumor cells in vitro by CB 1954, by a factor of 22. To demonstrate the specificity of this approach for tumor targeting, we intravenously injected the inactive spore form of C. beijerinckii, which upon transition to a reproductive state will express the E. coli nitroreductase gene. Nitroreductase activity was detectable in 10 of 10 tumors during the first 5 days after intravenous injection of inactive clostridial spores, indicating a rapid transition from spore to reproductive state. Tumors harboring clostridial spores which did not possess the E. coli nitroreductase gene were devoid of nitroreductase activity. Most importantly, E. coli nitroreductase protein was not found in a large survey of normal mouse tissues following intravenous injection of nitroreductase containing clostridia, strongly suggesting that obligate anaerobic bacteria such as clostridia can be utilized as highly specific gene delivery vectors for cancer therapy. 相似文献
109.
110.