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71.
Keeling KM Brooks DA Hopwood JJ Li P Thompson JN Bedwell DM 《Human molecular genetics》2001,10(3):291-299
Hurler syndrome is the most severe form of a lysosomal storage disease caused by loss of the enzyme alpha-L-iduronidase (encoded by the IDUA gene), which participates in the degradation of glycosaminoglycans (GAGs) within the lysosome. In some populations, premature stop mutations represent roughly two-thirds of the mutations that cause Hurler syndrome. In this study we investigated whether the aminoglycoside gentamicin can suppress stop mutations within the IDUA gene. We found that a Hurler syndrome fibroblast cell line heterozygous for the IDUA stop mutations Q70X and W402X showed a significant increase in alpha-L-iduronidase activity when cultured in the presence of gentamicin, resulting in the restoration of 2.8% of normal alpha-L-iduronidase activity. Determination of alpha-L-iduronidase protein levels by an immunoquantification assay indicated that gentamicin treatment produced a similar increase in alpha-L-iduronidase protein in Hurler cells. Both the alpha-L-iduronidase activity and protein level resulting from this treatment have previously been correlated with mild Hurler phenotypes. Although Hurler fibroblasts contain a much higher level of GAGs than normal, we found that gentamicin treatment reduced GAG accumulation in Hurler cells to a normal level. We also found that a reduced GAG level could be sustained for at least 2 days after gentamicin treatment was discontinued. The reduction in the GAG level was also reflected in a marked reduction in lysosomal vacuolation. Taken together, these results suggest that the suppression of premature stop mutations may provide an effective treatment for Hurler syndrome patients with premature stop mutations in the IDUA gene. 相似文献
72.
Detection of either rapidly cytolytic macrophages or NK cells in "activated" peritoneal exudates depends on the method of analysis and the target cell type 总被引:1,自引:1,他引:1 下载免费PDF全文
The nature of the cytotoxic cells present in the peritoneal cavity of rats treated with Bacille Calmette-Guérin (BCG) or Corynebacterium parvum was investigated using a 6 hr chromium release assay and a quantitative method of analysis based on consideration of target-cell killing as an enzyme-substrate reaction. When the results of cell-fractionation experiments were evaluated in terms of recovery of total lytic units and when appropriate target cells (such as sarcoma Mc7) were used, the simultaneous presence of both cytotoxic macrophages and NK cells in peritoneal exudates could be readily demonstrated. With certain other target cells different results were obtained. Thus, with normal thymocytes, normal hepatocytes, or myeloma P3NSI as targets, NK cells were preferentially detected, whereas with leukaemias L5178Y, P815, and EL4 as targets, cytotoxic macrophages were preferentially detected. These findings resolve the previously conflicting reports concerning the nature of cytotoxic cells in activated peritoneal exudates. 相似文献
73.
Glycogen synthesis and metabolism of lactic acid after exercise 总被引:1,自引:0,他引:1
74.
Waters DL Brooks WM Qualls CR Baumgartner RN 《Mechanisms of ageing and development》2003,124(3):301-309
BACKGROUND: The decline in muscle mass (sarcopenia) with aging may be related to a decline in mitochondrial function. However, investigators have yet to reach a consensus as to whether a decline in mitochondrial function can be attenuated by physical activity has yet to reach a consensus. METHODS: Using dynamic 31PMRS to measure mitochondrial function, we measured baseline Phosphocreatine (PCr), inorganic phosphate (Pi), phosphodiester (PDE), [ADP], pH and recovery times (t(1/2)) for PCr and [ADP] following exercise, in 45 older (73+/-4 years, SD), and 20 younger subjects (25+/-4 years, SD) who were matched for body mass across high and low activity levels and within age and sex groupings. RESULTS: Baseline PCr, and Pi, were lower, and PDE higher in the older subjects compared to younger subjects (all P<0.01). The t(1/2)(ADP) was longer in older subjects (P<0.001) controlling for age and sex in the low activity group (P=0.02). In the older low activity groups, t(1/2)(PCr) was longer than high activity groups. Higher PDE levels were positively correlated with longer t(1/2)(PCr) in the older low activity females (both P<0.05). CONCLUSIONS: Our data suggests that mitochondrial function declines with age in healthy, exercising elderly adults and that the decline appears to be influenced by the level of physical activity. 相似文献
75.
S. Brooks M. E. Nevill L. Meleagros H. K. A. Lakomy G. M. Hall S. R. Bloom C. Williams 《European journal of applied physiology》1990,60(2):144-148
Summary The responses of nine men and nine women to brief repetitive maximal exercise have been studied. The exercise involved a 6-s sprint on a non-motorised treadmill repeated 10 times with 30 s recovery between each sprint. The total work done during the ten sprints was 37,693±3,956 J by the men and 26,555±4,589 J by the women (M > F,P<0.01). This difference in performance was not associated with higher blood lactate concentrations in the men (13.96± 1.70 mmol·–1) than the women (13.09±3.04 mmol·l–1). An 18-fold increase in plasma adrenaline (AD) occurred with the peak concentration observed after five sprints. The peak AD concentration in the men was larger than that seen in the women (9.2 +- 7.3 and 3.7 ± 2.4 nmol · l–1 respectively,P<0.05). The maximum noradrenaline (NA) concentration occurred after ten sprints in the men (31.6±10.9 nmol·l–1) and after five sprints in the women (27.4 ± 20.8 nmol · l–1). Plasma cardiodilatin (CDN) and atrial natriuretic peptide (ANP) concentrations were elevated in response to the exercise. The peak ANP concentration occurred immediately postexercise and the response of the women (10.8 ± 4.5 pmol · l–1 was greater than that of the men (5.1 ± 2.6 pmol · l–1,P<0.05). The peak CDN concentrations were 163 ± 61 pmol · l–1 for the women and 135 ± 61 pmol · l–1 for the men. No increases in calcitonin gene related peptide (CGRP) were detected in response to the exercise. These results indicate differences between men and women in performance and hormonal responses. There was no evidence for a role of CGRP in the control of the cardiovascular system after brief intermittent maximal exercise. 相似文献
76.
Opa (protein II) influences gonococcal organization in colonies, surface appearance, size and attachment to human fallopian tube tissues 总被引:3,自引:0,他引:3
Opa-expressing variants of Neisseria gonorrhoeae strain F62-SF and an Opa- variant, all non-piliated, were examined for differences in the interaction of the bacteria within colonies and in attachment to and damage of human fallopian tube mucosa. Expression of certain Opas was associated with the formation of transparent colonies where the bacteria were tightly packed and evenly spaced within the colonies. Expression of other Opas was associated with the formation of opaque colonies where the gonococci were less tightly packed and were unevenly spaced. Distinct differences in the size of the gonococci and in their surface characteristics were dependent upon the Opa being expressed. Certain Opas were associated with gonococci that had significantly larger cross-sectional areas and bigger perimeters. Scanning electron microscopy showed that OpaC- and OpaD-containing variants yielded greater mucosal damage than OpaB-containing and Opa- variants with the least damage caused by the OpaA-containing variant (clumped bacteria from dark opaque friable colonies). The mucosal damage after 60 min incubation included shortening and decreased numbers of microvilli on non-ciliated cells and invagination and sloughing of ciliated cells. Differences in the interactions of gonococci within colonies and in attachment to fallopian tube mucosa and damage to the mucosal cells occurred with different Opa-expressing variants of N. gonorrhoeae strain F62-SF. 相似文献
77.
D R Hunt A Maslovitz B J Rowlands B Brooks 《Journal of the American Dietetic Association》1985,85(3):332-335
Nutrition screening is the process of identifying hospital patients with a high risk for nutrition problems who may require comprehensive nutrition assessment. Dietitians at a 700-bed teaching hospital recently implemented a nutrition screening program remarkable for efficient use of existing personnel resources. The three-step procedure includes a nutrition questionnaire completed by the patient in the hospital admissions office, measurement of each patient's height and weight by an admissions nurse, and addition of the patient's serum albumin concentration plus summary and recommendations for nutrition intervention by a registered dietitian. The procedure reduces the time needed for individual evaluation from 25 to 5 minutes and results in 1 1/2-hour time saving per day per clinical dietitian. Patients designated as "high risk" by this method appear to be more seriously ill, as shown by significantly longer hospitalization. The nutrition screening procedure described is simple, efficient, and applicable to a wide variety of institutional settings. 相似文献
78.
Ray L. Hanson Alan R. Dahl Simon J. Rothenberg Janet M. Benson Antone L. Brooks John S. Dutcher 《Archives of environmental contamination and toxicology》1985,14(3):289-297
Volatile components from diesel exhaust particles and coal gasifier process gas condensate were vacuum fractionated by cryogenic distillation and identified by infrared spectroscopy and gas chromatography/mass spectrometry. The vacuum distillation line consisted of a sample flask and nine traps cooled from 0°C to ?196°C in approximately 20°C steps. The pressure in the vacuum line of about 10?2 Torr was maintained with a vacuum pump. Separated compounds were identified by comparison to reference infrared spectra and confirmed by comparison with standards when practical. Volatile compounds identified from the diesel exhaust particle sample included NOx, carbon dioxide, sulfur dioxide, alkanes, aldehydes, and one and two ring aromatic hydrocarbons. Volatile compounds identified in process gas condensate from a coal gasifier were ammonia, carbonyl sulfide, carbon dioxide, C3-C7 hydrocarbons, one and two ring aromatic hydrocarbons, and phenols. Volatile components collected at either 0° or ?24°C were evaluated to determine their genotoxicity using the Chinese hamster ovary/hypoxanthine-guanine phosphoribosyltransferase (CHO/HGPRT) assay. Neither the gasifier condensate nor diesel particle samples produced mutations at the HGPRT locus. The diesel samples were not cytotoxic at the concentrations tested (100 μg/ml) but the gasifier samples resulted in 50% cell killing at concentrations between 25 and 100 μg/ml depending on the temperature of collection and the test conditions. Vacuum desorption with cryogenic distillation has provided a means to separate the volatile components in complex environmental samples to allow chemical and biological characterization of these components. 相似文献
79.
80.
Three measures of lower extremity function were compared in a homogenous population of ALS patients. Isokinetic dynamometry was shown to be a sensitive tool for change in strength over time. It demonstrated positive correlations with gait velocity as well as other behavioral measures. Manual muscle tests were relatively insensitive and no more reliable than isokinetics. Isokinetics are a useful adjunct in the assessment of ALS. 相似文献