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71.
72.
Heare T Alp NJ Priestman DA Kulkarni AB Qasba P Butters TD Dwek RA Clarke K Channon KM Platt FM 《Journal of inherited metabolic disease》2007,30(1):79-87
Summary
Objective: Fabry disease results from α-gala- ctosidase A deficiency and is characterized by the lysosomal accumulation of globotriaosylceramide.
Globotriaosylceramide storage predominantly affects endothelial cells, altering vascular wall morphology and vasomotor function.
Our objective was to investigate aortic globotriaosylceramide levels, morphology and function in a mouse model of Fabry disease,
and the effect of substrate reduction therapy, using the glycosphingolipid biosynthesis inhibitor N-butyldeoxynojirimycin. Methods and results: Mice used were C57BL/6J and α-galactosidase A knockout (Fabry). We show progressive accumulation of aortic globotriaosylceramide
throughout the lifespan of untreated Fabry mice (55-fold elevation at 2 months increasing to 187-fold by 19 months), localized
to endothelial and vascular smooth-muscle cells; there was no effect on vascular wall morphology in young Fabry mice. In old
mice, storage resulted in intimal thickening. Endothelial function declined with age in Fabry mouse aorta. Aortae from N-butyldeoxynojirimycin-treated Fabry mice at 19 months of age had reduced endothelial globotriaosylceramide storage, fewer
morphological abnormalities and less severe vasomotor dysfunction compared with untreated littermates. Conclusion: We provide evidence of a novel vascular phenotype in the Fabry mouse that has relevance to vascular disease in Fabry patients.
N-Butyldeoxynojirimycin treatment partially prevented the phenotype in the Fabry mouse by reducing endothelial globotriaosylceramide
storage. 相似文献
73.
Ajit Sood Vandana Midha Omesh Goyal Prerna Goyal Pramod Sood Suresh Kumar Sharma Neena Sood 《Indian journal of gastroenterology》2014,33(3):281-284
Skin and soft tissue infections (SSTI) are an important cause of morbidity and mortality in patients with cirrhosis. This prospective study aimed to analyze the clinical profile and factors affecting outcome of SSTIs in cirrhotics. All cirrhotics hospitalized between September 2007 and August 2010 were included. Frequency, site, extent, and type of SSTI were noted. Of 1,395 cirrhotics, 19.4 % (n = 271) had bacterial infections, out of which 32.8 % (89/271) had SSTI. Alcohol was the predominant etiological factor for cirrhosis; 95.2 % belonged to Child class B/C, and 67 % gave history of barefoot walking. The most common site of SSTI was the lower limbs (87.1 %), cellulitis was the most common type (61.2 %), and gram-negative bacilli (GNB) is the most common organism (86.7 %). Mortality rate was 23.5 %. Serum creatinine and model for end-stage liver disease (MELD) score were independent predictors of mortality. SSTIs in cirrhotics were common and mostly involved the lower limbs. Cellulitis was the most common type, and GNB was the most common organism. Serum creatinine and MELD score were independent predictors of mortality. 相似文献
74.
Reactions of α-Aminoacetonitriles with metallic Sodium in Toluene When α-aminonitriles are treated with metallic sodium in toluene the CN-group is replaced by hydrogen or by the CN-free part of a second aminonitrile molecule. The reaction mechanisms and their dependence on the structure of the aminonitrile are discussed. 相似文献
75.
Patterns of gene expression in normal and neoplastic rat mammary tissues were compared by cell-free translation of their total polyadenylated RNAs and by dot blot hybridization of the RNA to cloned complementary DNA probes for six of the major milk proteins, including: Mr 42,000 and 25,000 caseins, X-casein, whey phosphoproteins, kappa-proteins, and alpha-lactalbumin. Distinct but overlapping messenger RNA populations were evident from the translation patterns of normal virgin, pregnant, and lactating mammary glands. Dot blot analysis showed that each milk protein RNA had a different characteristic accumulation profile during pregnancy and lactation. The MTW9 and MCCLX mammary tumor lines, which are transplantable, prolactin dependent for growth, and produce alpha-lactalbumin, both showed high alpha-lactalbumin and Mr 42,000 casein messenger RNA activity. The tumors also had other milk protein RNA sequences, although in different proportions than at any stage during functional differentiation of normal adult mammary gland. Our results indicate that normal pregnant mammary gland expresses all of the abundant milk protein genes prior to detectable milk secretion. The patterns of gene expression in the two mammary tumors do not appear to correspond to any particular stage of functional differentiation of the normal mammary gland. 相似文献
76.
BERT PH. M. Menco ANNE M. Cunningham PANKAJ Qasba NINA Levy RANDALL R. Reed 《Journal of neurocytology》1997,26(10):691-706
Two different polyclonal antibodies were raised to synthetic peptides corresponding to distinct putative odour receptors of rat and mouse. Both antibodies selectively labelled olfactory cilia as seen with cryofixation and immunogold ultrastructural procedures. Regions of the olfactory organ where label was detected were consistent with those found at LM levels. Immunopositive cells were rare; only up to about 0.4% of these receptor cells were labelled. Despite chemical, species, and topographic differences both antibodies behaved identically in their ultrastructural labelling patterns. For both antibodies, labelling was very specific for olfactory cilia; both bound amply to the thick proximal and the thinner and long distal parts of the cilia. Dendritic knobs showed little labelling if any. Dendritic receptor cell structures below the knobs, supporting cell structures, and respiratory cilia did not immunolabel. There were no obvious differences in morphology between labelled and unlabelled receptor cells and their cilia. Labelling could be followed up to a distance of about 15 m from the knobs along the distal parts of the cilia. When labelled cells were observed, this signal was detectable in two, sometimes three, sections taken through these cells while being consistently absent in neighbouring cells. This pattern argues strongly for the specificity of the labelling. In conclusion, very few receptor cells labelled with the antibodies to putative odour receptors. Additionally the olfactory cilia, the cellular regions that first encounter odour molecules and that are thought to transduce the odorous signal, displayed the most intense labelling with both antibodies. Consequently, the results showed these cilia as having many copies of the putative receptors. Finally, similar patterns of subcellular labelling were displayed in two different species, despite the use of different antibodies. Thus, this study provides compelling evidence that the heptahelical putative odour receptors localize in the olfactory cilia. 相似文献
77.
PURPOSE: To compare intraocular pressure (IOP) and rates of postoperative hypotony with 25-gauge pars plana vitrectomy (PPV) without tamponade using oblique versus direct cannula insertions. METHODS: A prospective consecutive series of eyes that underwent 25-gauge PPV without tamponade using an oblique cannula insertion technique was compared with a historical consecutive series of eyes that underwent 25-gauge PPV without tamponade using direct cannula insertions. IOP was recorded before surgery, on postoperative day 1, and on postoperative week 1. RESULTS: Ninety-five eyes had 25-gauge PPV without tamponade, 55 with oblique cannula insertions and 40 with direct insertions. With oblique insertions, there was no statistically significant difference between mean IOPs measured before surgery, on postoperative day 1, and on postoperative week 1. Only 1 (1.8%) of the 55 eyes had hypotony (IOP, 相似文献
78.
The availability of structural information on glycosyltransferases is beginning to make structure-based reengineering of these enzymes possible. Mutant glycosyltransferases have been generated that can transfer a sugar residue with a chemically reactive unique functional group to a sugar moiety of glycoproteins, glycolipids, and proteoglycans (glycoconjugates). The presence of modified sugar moiety on a glycoprotein makes it possible to link bioactive molecules via modified glycan chains, thereby assisting in the assembly of bionanoparticles that are useful for developing the targeted drug delivery system and contrast agents for magnetic resonance imaging. The reengineered recombinant glycosyltransferases also make it possible to (1) remodel the oligosaccharide chains of glycoprotein drugs, and (2) synthesize oligosaccharides for vaccine development. 相似文献
79.
DNA and Gene Therapy: Transfer of Mouse DNA to Human and Mouse Embryonic Cells by Polyoma Pseudovirions 总被引:8,自引:1,他引:7 下载免费PDF全文
Pradman K. Qasba H. Vasken Aposhian 《Proceedings of the National Academy of Sciences of the United States of America》1971,68(10):2345-2349
It was demonstrated previously that polyoma pseudovirions (DNA fragments encapsidated by polyoma virus coats) are adsorbed to and uncoated by mouse-embryo cells. 24 hr after infection of secondary mouse-embryo cells with [(3)H]thymidine-labeled pseudovirus, 24% of the total radioactivity found in cells occurred in the nuclear fraction. This nuclear radioactivity represents pseudovirus DNA, as shown by its hybridization with mouse-embryo DNA. Since much of the radioactive material found in the nuclear fraction is sensitive to pancreatic DNase, it is available as uncoated DNA.24 hr after infection of human embryo cells with [(3)H]thymidine-labeled pseudovirions, 7% of the total cellular radioactivity is found in the nuclear fraction of the cells. That this radioactivity represents uncoated pseudoviral DNA was shown by sedimentation of the disrupted nuclear fraction through a neutral sucrose gradient. The pseudoviral DNA in the nuclear fraction has been nicked to some extent, as shown by the heterogeneity of the peaks found after sedimentation of the disrupted nuclear fraction through alkaline sucrose. The experiments demonstrate that polyoma pseudovirions deliver DNA to human cells. 相似文献
80.
Bajpai Omesh Dutta Venkatesh Singh Rachna Chaudhary L. B. Pandey Jitendra 《Proceedings of the National Academy of Sciences, India. Section B.》2020,90(4):873-883
Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - The Himalayan foothills in northern India form one of the distinct eco-climatic regions of the world which... 相似文献