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101.
Muscle-specific mutations accumulate with aging in critical human mtDNA control sites for replication 总被引:15,自引:0,他引:15 下载免费PDF全文
Wang Y Michikawa Y Mallidis C Bai Y Woodhouse L Yarasheski KE Miller CA Askanas V Engel WK Bhasin S Attardi G 《Proceedings of the National Academy of Sciences of the United States of America》2001,98(7):4022-4027
The recently discovered aging-dependent large accumulation of point mutations in the human fibroblast mtDNA control region raised the question of their occurrence in postmitotic tissues. In the present work, analysis of biopsied or autopsied human skeletal muscle revealed the absence or only minimal presence of those mutations. By contrast, surprisingly, most of 26 individuals 53 to 92 years old, without a known history of neuromuscular disease, exhibited at mtDNA replication control sites in muscle an accumulation of two new point mutations, i.e., A189G and T408A, which were absent or marginally present in 19 individuals younger than 34 years. These two mutations were not found in fibroblasts from 22 subjects 64 to 101 years of age (T408A), or were present only in three subjects in very low amounts (A189G). Furthermore, in several older individuals exhibiting an accumulation in muscle of one or both of these mutations, they were nearly absent in other tissues, whereas the most frequent fibroblast-specific mutation (T414G) was present in skin, but not in muscle. Among eight additional individuals exhibiting partial denervation of their biopsied muscle, four subjects >80 years old had accumulated the two muscle-specific point mutations, which were, conversely, present at only very low levels in four subjects < or =40 years old. The striking tissue specificity of the muscle mtDNA mutations detected here and their mapping at critical sites for mtDNA replication strongly point to the involvement of a specific mutagenic machinery and to the functional relevance of these mutations. 相似文献
102.
Plasma aspirin esterase: the influence of old age and frailty 总被引:3,自引:0,他引:3
Plasma aspirin esterase activity, expressed as nmol salicylate formed/ml plasma/min, was found to be similar in a group of healthy elderly adults, a group of young adults and a group of frail young adults, but was lower in a sample of frail elderly subjects. This was associated with reduced plasma albumin levels in healthy elderly subjects compared with young subjects and levels were lower still in the frail elderly group. Plasma cholinesterase also showed a trend towards reduced activity in the frail elderly subjects. As plasma aspirin esterase activity may influence the amount of circulating aspirin, these changes may have implications for the use of aspirin in frail elderly people. 相似文献
103.
Woodhouse LJ Gupta N Bhasin M Singh AB Ross R Phillips J Bhasin S 《The Journal of clinical endocrinology and metabolism》2004,89(2):718-726
Testosterone supplementation reduces total body adipose tissue (AT), but we do not know whether the effects are uniformly distributed throughout the body or are region specific, or whether they are dose related. We determined the effects of graded doses of testosterone on regional AT distribution in 54 healthy men (18-35 yr) in a 20-wk, randomized, double-blind study of combined treatment with GnRH agonist plus one of five doses (25, 50, 125, 300, or 600 mg/wk) of testosterone enanthate (TE). Total body, appendicular, and trunk AT and lean body mass were measured by dual-energy x-ray absorptiometry, and sc, intermuscular, and intraabdominal AT of the thigh and abdomen were measured by magnetic resonance imaging. Treatment regimens resulted in serum nadir testosterone concentrations ranging from subphysiological to supraphysiological levels. Dose-dependent changes in AT mass were negatively correlated with TE dose at all sites and were equally distributed between the trunk and appendices. The lowest dose was associated with gains in sc, intermuscular, and intraabdominal AT, with the greatest percent increase occurring in the sc stores. At the three highest TE doses, thigh intermuscular AT volume was significantly reduced, with a greater percent loss in intermuscular than sc depots, whereas intraabdominal AT stores remained unchanged. In conclusion, changes in testosterone concentrations in young men are associated with dose-dependent and region-specific changes in AT and lean body mass in the appendices and trunk. Lowering testosterone concentrations below baseline increases sc and deep AT stores in the appendices and abdomen, with a greater percent increase in sc depots. Conversely, elevating testosterone concentrations above baseline induces a greater loss of AT from the smaller, deeper intermuscular stores of the thigh. 相似文献
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106.
Nabin Paudel BOptom Susan J Leat PhD FCOptom FAAO Prakash Adhikari BOptom J Margaret Woodhouse PhD Jyoti Baba Shrestha MD 《Clinical & experimental optometry》2010,93(2):83-90
Background: Down syndrome (DS) is a common chromosomal anomaly. People with this syndrome have recognisable physical characteristics and limited intellectual abilities. The aim of this study was to determine visual defects, especially refractive error and binocular anomalies, in a sample of Nepalese children with DS. Methods: Thirty‐six children with DS (19 boys and 17 girls) from the Kathmandu valley, aged from four months to 18 years, underwent detailed optometric examination. Cycloplegic refraction was performed on all subjects. Vision on presentation of all the children was assessed with preferential looking cards, the Kay picture cards, the Bailey‐Lovie logMAR chart or the Snellen chart. Binocular function was assessed with cover test, Hirschberg or Bruckner test. Results: Cycloplegic refraction of the children revealed that 80 per cent of the children had significant refractive error. Most of them had hyperopia (55 per cent), followed by astigmatism (44 per cent), myopia (25 per cent) and anisometropia (19 per cent). Only two (5.6 per cent) children were strabismic and both of them were alternating esotropes. Nystagmus was present in 10 (28 per cent). Other ocular findings were upward slanting palpebral fissures, blepharitis, congenital nasolacrimal duct obstruction, blepharoconjunctivitis, chalazion and lenticular opacities. Conclusion: Nepalese children with DS have a high prevalence of refractive error and nystagmus. Regular eye examinations are indicated for these children to enable early diagnosis and appropriate management of ocular disorders to improve their vision and quality of life. 相似文献
107.
van Beek EJ Hill C Woodhouse N Fichele S Fleming S Howe B Bott S Wild JM Taylor CJ 《European radiology》2007,17(4):1018-1024
This study assesses the feasibility of hyperpolarized 3-Helium MRI in children with cystic fibrosis (CF) and correlates the
findings with standard clinical parameters based on chest radiograph (CXR) and pulmonary function tests (PFT). An uncontrolled,
observational study in eighteen children with cystic fibrosis aged 5 – 17 years (median 12.1 years), with different severity
of disease was carried out. All subjects underwent routine clinical assessment including PFT and standard auxology; CXR was
obtained and Shwachman and Chrispin-Norman scores calculated. Hyperpolarized 3-He magnetic resonance imaging (MRI) was carried
out using a spin-exchange polarizer and a whole body 1.5 T scanner. Ventilation distribution images were obtained during a
21-second breath-hold and scored according to previously defined criteria. Spearman’s non-parametric correlations test was
performed to assess for statistical significance at the p<0.05 level. The children tolerated the procedure well. No desaturation
events were observed during 3-He MRI. A significant, albeit moderate, correlation was found between MRI score and FEV1% predicted
(r=−0.41; p=0.047) and FVC% predicted (r=−0.42; p=0.04), while there were trends of correlations between Shwachman score and
MRI score (r=−0.38; p=0.06) and Shwachman score and FEV1% predicted (r=0.39; p=0.055). The feasibility of hyperpolarized 3-He
MRI in children with CF was demonstrated. MRI appears to be able to demonstrate functional lung changes, although correlations
with routine clinical tests are only moderate to poor. This non-ionising radiation technique could be useful for monitoring
lung disease and assessing therapy in this patient population. 相似文献
108.
STUDY DESIGN.: An in vitro biomechanical and imaging study generated from an in vivo porcine model of early stage degenerative disc disease was used to evaluate mechanical property restoration, comparing 2 minimally invasive injection techniques. OBJECTIVE.: To evaluate the ability of an injectable hydrogel to restore the mechanical properties of spinal motion segments with early stage disc degeneration, comparing 2 minimally invasive injection techniques. SUMMARY OF BACKGROUND DATA.: Treatment of early-stage disc degeneration may benefit from a combination of tissue engineering and minimally invasive therapeutic approaches. A recently developed hydrogel, thiol-modified hyaluronan elastin-like polypeptide (TMHA/EP) composite, has demonstrated potential as an injectable nucleus replacement. METHODS.: From a total of thirteen 35-kg Yorkshire boars, early-stage lumbar disc degeneration was introduced into 10 pigs via injection of chondroitinase ABC. After degeneration, 8 pigs received TMHA/EP augmentation; 1 disc via direct needle injection and a second using a modified kyphoplasty approach. High-resolution magnetic resonance images were acquired of the excised spinal motion segments, followed by biomechanical testing in axial compression, flexion-extension, lateral bending, and torsion. RESULTS.: The degenerate control motion segments were generally less stiff and more flexible than healthy controls. The injection of TMHA/EP into the degenerated nucleus produced similar mechanical stiffness to healthy controls. The direct-injected discs showed a dispersive pattern of TMHA/EP within the nucleus, whereas the modified kyphoplasty method yielded a bolus of hydrogel. Yet, mechanical behavior was comparable considering the 2 minimally invasive augmentation techniques. CONCLUSION.: The TMHA/EP composite can restore initial mechanical behavior in early-stage disc degeneration. Although both augmentation methods yielded mechanical properties comparable with healthy controls, direct injection represents a simpler technique, uses a smaller-gauge needle, does not introduce air into the disc, and yields a dispersive pattern that may be beneficial for future delivery of cells or growth factors. 相似文献
109.
Age and the metabolism of drugs 总被引:1,自引:0,他引:1
M D Rawlins O F James F M Williams H Wynne K W Woodhouse 《The Quarterly journal of medicine》1987,64(243):545-547
110.