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121.
Frequency and coverage of trinucleotide repeats in eukaryotes 总被引:3,自引:0,他引:3
In the aim to assess whether the tri-repeat shortage reported in vertebrates affects specific motifs, such as those causing neuromuscular diseases in man, we detected approximate di-, tri- and tetra-repeats (STR) longer than 25 bases in human chromosomes 21 and 22, and in some model organisms (M. musculus, D. melanogaster, C. elegans, A. thaliana and S. cerevisiae). We found that overall STR are more represented in mouse and in man than in the other organisms. However, tri-repeats are less represented than di- and tetra- in man and mouse, but show intermediate values between di- and tetra- in the other organisms. In man, ACG shows the lowest both frequency and coverage, ATC the highest coverage and AAT the highest frequency. In general, coverage and frequency of tri-repeats are linearly related, except for ACC, ATC, AAG, AGG motifs in man and AAG, AGG in mouse, which exhibit unexpectedly long repeats. Often their copy numbers exceed that found responsible for the dynamic mutations, set at around 40. The shortage in frequency and coverage of tri- vs. di- and tetra-repeats observed in man and mouse can be ascribed to a subset of the remaining tri-repeat motifs, but among them those recognized as dynamically mutable (AAG, AGC and CCG) are not the least represented. Possible constraints in tri-repeat expansion seem to be structural and conserved along the evolutionary scale: a motif-specific relaxation of the relevant controls may be responsible for the occasional expansions found in mouse and man. 相似文献
122.
123.
Bradbury A Velappan N Verzillo V Ovecka M Chasteen L Sblattero D Marzari R Lou J Siegel R Pavlik P 《Trends in biotechnology》2003,21(7):312-317
There are many ways in which the use of antibodies and antibody selection can be improved and developed for high-throughput characterization. Standard protocols, such as immunoprecipitation, western blotting and immunofluorescence, can be used with antibody fragments generated by display technologies. Together with novel approaches, such as antibody chips and intracellular immunization, these methods will yield useful proteomic data following adaptation of the protocols for increased reliability and robustness. To date, most work has focused on the use of standard, well-characterized commercial antibodies. Such protocols need to be adapted for broader use, for example, with antibody fragments or other binders generated by display technologies, because it is unlikely that traditional approaches will provide the required throughput. 相似文献
124.
Drug treatment in the development of mismatch repair defective acute leukemia and myelodysplastic syndrome 总被引:5,自引:0,他引:5
Casorelli I Offman J Mele L Pagano L Sica S D'Errico M Giannini G Leone G Bignami M Karran P 《DNA Repair》2003,2(5):547-559
DNA from therapy-related acute leukemia/myelodysplastic syndrome cases (tAL/MDS) from the GIMEMA [Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto] Archive was examined for the microsatellite instability (MSI(+)) phenotype that is diagnostic for defective DNA mismatch repair. More than 60% (16/25) of tAL/MDS cases were MSI(+) in contrast to <4% (0/28) of de novo cases. hMLH1 gene silencing was rare and evidence of promoter methylation was found in less than one-third of the MSI(+) cases. Among the GIMEMA patients who had been treated for breast cancer there was an apparent trend towards early onset primary breast disease. This suggests that there might be common predisposing factors for breast cancer and tAL/MDS. There were also three examples of mutations in the MRE11 gene among the 25 tAL/MDS cases suggesting that defective recombinational DNA repair may promote the development of secondary malignancy. MSI(+) tAL/MDS was significantly associated with previous chemotherapy and the frequency of MSI(+) among radiotherapy patients was considerably lower. In view of the established relationship between drug resistance and mismatch repair defects, we suggest that selection for therapeutic drug resistance may contribute to the incidence of MSI(+) tAL/MDS. 相似文献
125.
Kennergren C Mantovani V Strindberg L Berglin E Hamberger A Lonnroth P 《American journal of physiology. Endocrinology and metabolism》2003,284(4):E788-E794
The interstitial fluid of the human myocardium was monitored in 13 patients undergoing aortic valve and/or bypass surgery before, during, and after hypothermic potassium cardioplegia. The regulation of glucose and lactate was studied after sampling with microdialysis. The following questions were addressed. 1). Is the rate of transcapillary diffusion the limiting step for myocardial uptake of glucose before or after cardioplegia? 2). Does cold potassium cardioplegia induce a critical deprivation of glucose and/or accumulation of lactate in the myocardium? Before cardioplegia, interstitial glucose was approximately 50% of the plasma level (P < 0.001). Interstitial glucose decreased significantly immediately after induction of cardioplegia and remained low (1.25 +/- 0.25 mM) throughout cardioplegia. It was restored to precardioplegic levels 1 h after release of the aortic clamp. Interstitial glucose then decreased again at 25 and 35 h postoperatively to the levels observed during cardioplegia. Interstitial lactate decreased immediately after induction of cardioplegia but returned to basal level during the clamping period. At 25 and 35 h, interstitial lactate was significantly lower than before and during cardioplegia. Glucose transport over the capillary endothelium is considered rate limiting for its uptake in the working heart but not during cold potassium cardioplegia despite the glucose deprivation following perfusion of glucose-free cardioplegic solution. Lactate accumulated during cardioplegia but never reached exceedingly high interstitial levels. We conclude that microdialysis provides information that may be relevant for myocardial protection during open-heart surgery. 相似文献
126.
Antiendotoxin activity of protegrin analog IB-367 alone or in combination with piperacillin in different animal models of septic shock 总被引:1,自引:0,他引:1
Giacometti A Cirioni O Ghiselli R Mocchegiani F Viticchi C Orlando F D'Amato G Del Prete MS Kamysz W łLukasiak J Saba V Scalise G 《Peptides》2003,24(11):1747-1752
The therapeutic efficacy of protegrin peptide IB-367 was investigated in three rat models of septic shock: (i) rats injected intraperitoneally with 1mg Escherichia coli 0111:B4 lipopolysaccharide, (ii) rats given an intraperitoneal injection of 2 X 10(10) CFU of E. coli ATCC 25922, and (iii) rats in which intra-abdominal sepsis was induced via cecal ligation and puncture. All animals were randomized to receive parenterally isotonic sodium chloride solution, 1mg/kg of IB-367, 60mg/kg piperacillin and 1mg/kg of IB-367 plus 60mg/kg piperacillin. The peptide demonstrated lower level of antimicrobial activity than piperacillin, nevertheless it exhibited the dual properties of antimicrobial and antiendotoxin agent. Finally IB-367 and piperacillin association showed to be the most effective therapeutic approach. 相似文献
127.
128.
We report a kinetic study on thermal aggregation process of the model protein bovine serum albumin (BSA) in low concentration regime. Aim of this study is to provide information on relationship between conformational changes and initial step of aggregation. The experimental approach is based on steady-state fluorescence spectra of the two tryptophans located in two different domains, in way to study conformational changes in the surrounding of these residues. We also follow emission spectra of Fluorescein-5-Maleimide dye bound to the single free cysteine of BSA. Complementary information on the extent of aggregation and on the structural changes is obtained by Rayleigh scattering and circular dichroism measurements. These data contribute to clarify the connection between conformational changes at tertiary and secondary structure level during the aggregation and how the different domains are involved. We also discuss the relevant role played by cysteine 34 in the aggregation pathways. 相似文献
129.
Battino M Bompadre S Leone L Pugnaloni A Rubini C Ferreiro MS Gallardo I Bullon P 《BioFactors (Oxford, England)》2003,18(1-4):271-275
Cyclosporine A (CsA) plays a pivotal role in controlling Ca2+ movement in the cell modulating also the mitochondrial permeability transition pore. We investigated if chronic administration of CsA may have some effects on the lipophilic and hydrophilic antioxidant pattern of rat liver mitochondria and on their morphological structure. It seems that CsA administration does not statistically affect the redox status of the antioxidants investigated and their amounts (vitamin E, CoQ9, CoQ10, glutathione, uric acid and ascorbic acid) despite the variety of effects that this treatment produces at physiological and morphological levels. However, some kind of derangement could occur in the liver biochemical machinery since CsA treatment induces a markedly increased variability in antioxidant contents. 相似文献
130.
Vonasek E Mateu L Luzzati V Marquez G Vargas R Céspedes G Cotúa M Borges J 《European biophysics journal : EBJ》2001,30(1):11-16
A sural nerve dissected from a recently dead patient displayed an unusual X-ray diffraction pattern, suggesting that in situ and at the time of the patient's death the myelin sheaths were in a swollen state. Diffraction patterns of the swollen type were also recorded from: (1) a sural nerve from the corpse of a neurologically healthy person after soaking the nerve with Ringer solution at pH 5.5; (2) sciatic nerves dissected from rat cadavers at increasing time after death. In all the cases the swollen patterns reversed to the native type upon superfusion with Ringer solution at pH 7.3. The postmortem effect is to decrease the pH of the fluids surrounding the nerves in the cadavers. Our experiments show that the early postmortem processes have the effect of acidifying PNS nerves and that as a consequence of acidification the myelin sheaths swell. 相似文献