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71.
Assessment of aldehyde dehydrogenase in viable cells 总被引:3,自引:4,他引:3
Jones RJ; Barber JP; Vala MS; Collector MI; Kaufmann SH; Ludeman SM; Colvin OM; Hilton J 《Blood》1995,85(10):2742-2746
Cytosolic aldehyde dehydrogenase (ALDH), an enzyme responsible for oxidizing intracellular aldehydes, has an important role in ethanol, vitamin A, and cyclophosphamide metabolism. High expression of this enzyme in primitive stem cells from multiple tissues, including bone marrow and intestine, appears to be an important mechanism by which these cells are resistant to cyclophosphamide. However, although hematopoietic stem cells (HSC) express high levels of cytosolic ALDH, isolating viable HSC by their ALDH expression has not been possible because ALDH is an intracellular protein. We found that a fluorescent aldehyde, dansyl aminoacetaldehyde (DAAA), could be used in flow cytometry experiments to isolate viable mouse and human cells based on their ALDH content. The level of dansyl fluorescence exhibited by cells after incubation with DAAA paralleled cytosolic ALDH levels determined by Western blotting and the sensitivity of the cells to cyclophosphamide. Moreover, DAAA appeared to be a more sensitive means of assessing cytosolic ALDH levels than Western blotting. Bone marrow progenitors treated with DAAA proliferated normally. Furthermore, marrow cells expressing high levels of dansyl fluorescence after incubation with DAAA were enriched for hematopoietic progenitors. The ability to isolate viable cells that express high levels of cytosolic ALDH could be an important component of methodology for identifying and purifying HSC and for studying cyclophosphamide-resistant tumor cell populations. 相似文献
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73.
Erik P A van Iperen Suthesh Sivapalaratnam S Matthijs Boekholdt G Kees Hovingh Stephanie Maiwald Michael W Tanck Nicole Soranzo Jonathan C Stephens Jennifer G Sambrook Marcel Levi Willem H Ouwehand John JP Kastelein Mieke D Trip Aeilko H Zwinderman 《European journal of human genetics : EJHG》2014,22(6):809-813
In recent years, multiple loci dispersed on the genome have been shown to be associated with coronary artery disease (CAD). We investigated whether these common genetic variants also hold value for CAD prediction in a large cohort of patients with familial hypercholesterolemia (FH). We genotyped a total of 41 single-nucleotide polymorphisms (SNPs) in 1701 FH patients, of whom 482 patients (28.3%) had at least one coronary event during an average follow up of 66 years. The association of each SNP with event-free survival time was calculated with a Cox proportional hazard model. In the cardiovascular disease risk factor adjusted analysis, the most significant SNP was rs1122608:G>T in the SMARCA4 gene near the LDL-receptor (LDLR) gene, with a hazard ratio for CAD risk of 0.74 (95% CI 0.49–0.99; P-value 0.021). However, none of the SNPs reached the Bonferroni threshold. Of all the known CAD loci analyzed, the SMARCA4 locus near the LDLR had the strongest negative association with CAD in this high-risk FH cohort. The effect is contrary to what was expected. None of the other loci showed association with CAD. 相似文献
74.
Katherine JP Schwenger Johane P Allard 《World journal of gastroenterology : WJG》2014,20(7):1712-1723
Non-alcoholic fatty liver disease(NAFLD)ranges from simple steatosis to nonalcoholic steatohepatitis(NASH),leading to fibrosis and potentially cirrhosis,and it is one of the most common causes of liver disease worldwide.NAFLD is associated with other medical conditions such as metabolic syndrome,obesity,cardiovascular disease and diabetes.NASH can only be diagnosed through liver biopsy,but noninvasive techniques have been developed to identify patients who are most likely to have NASH or fibrosis,reducing the need for liver biopsy and risk to patients.Disease progression varies between individuals and is linked to a number of risk factors.Mechanisms involved in the pathogenesis are associated with diet and lifestyle,influx of free fatty acids to the liver from adipose tissue due to insulin resistance,hepatic oxidative stress,cytokines production,reduced very low-density lipoprotein secretion and intestinal microbiome.Weight loss through improved diet and increased physical activity has been the cornerstone therapy of NAFLD.Recent therapies such as pioglitazone and vitamin E have been shown to be beneficial.Omega 3 polyunsaturated fatty acids and statins may offer additional benefits.Bariatric surgery should be considered in morbidly obese patients.More research is needed to assess the impact of these treatments on a long-term basis.The objective of this article is to briefly review the diagnosis,management and treatment of this disease in order to aid clinicians in managing these patients. 相似文献
75.
Mice are a widely utilized in vivo model for translational salivary gland research but must be used with caution. Specifically, mouse salivary glands are similar in many ways to human salivary glands (i.e., in terms of their anatomy, histology, and physiology) and are both readily available and relatively easy and affordable to maintain. However, there are some significant differences between the two organisms, and by extension, the salivary glands derived from them must be taken into account for translational studies. The current review details pertinent similarities and differences between human and mouse salivary glands and offers practical guidelines for using both for research purposes. 相似文献
76.
Estimates of the viral residual risk should be updated to reflect current incidence of infection in blood donors. Incidence rates were estimated for allogeneic whole‐blood donations made to Canadian Blood Services from 2006 to 2009 based on transmissible disease conversions of repeat donations within a 3‐year period. Residual risk was estimated as the incidence multiplied by the window period. The residual risk of HIV was 1 per 8 million donations, HCV 1 per 6·7 million donations and HBV 1 per 1·7 million donations. The residual risk remains low and has decreased for HCV since our previous estimates due to reduced incidence. 相似文献
77.
Charles-Henri Flouzat-Lachaniette Jérôme Allain Françoise Roudot-Thoraval Alexandre Poignard 《European spine journal》2013,22(3):548-555
Purpose
To analyze the neurological and mechanical outcomes in 44 consecutive patients treated for a hematological malignancy with epidural localization to assess the place of surgery in the treatment of this pathology.Methods
Clinical records, CT and MRI scans of 44 patients with epidural localizations of multiple myeloma or lymphoma treated between 1990 and 2005 were analyzed retrospectively. Neurological status, epiduritis and osteolysis volumes, vertebral collapse, and spinal canal compromise were assessed. The neurological outcome was graded according to Frankel and the mechanical outcome was evaluated on the rate of vertebral collapse.Results
Surgery was performed in 11 patients (25 %) for neurological (n = 9) or mechanical (n = 2) reasons. In five cases, a concomitant biopsy was performed because the etiology of the epiduritis was unknown. Fifteen patients (34.1 %) presented with a neurological deficit secondary to an acute vertebral collapse (n = 4), an epiduritis (n = 7), or both (n = 4). Whatever the treatment (surgical or not), a complete recovery (Frankel E) occurred in 14/15 (93.3 %) after a mean delay of 12 weeks (range 2–24 weeks). During the follow-up, seven collapses occurred. We estimated that a threshold of 30 % of osteolysis was associated with a significant risk of vertebral collapse (P = 0.005).Conclusions
Hematological malignancies with epidural localization must be treated first medically, even in patients with neurological symptoms. Surgery should be considered only in the cases of acute vertebral collapse, medical treatment failure, or to prevent acute collapse in patients with vertebral osteolysis of more than 30 %. 相似文献78.
Philippe Hernigou Yasuhiro Homma Charles Henri Flouzat Lachaniette Alexandre Poignard Jerome Allain Nathalie Chevallier Helene Rouard 《International orthopaedics》2013,37(11):2279-2287
Purpose
Aspirating bone marrow from the iliac crest using small volumes of 1–4 ml with a 10-ml syringe has been historically proposed for harvesting adult mesenchymal stem cells and described as a standard technique to avoid blood dilution. The disadvantage of repeated small aspirations is that there is a significantly increased time to harvest the bone marrow. However, it is not known if a large volume syringe can improve the rate of bone marrow aspiration without increasing blood dilution, thus reducing the quality of the aspirate. We compared the concentrations of mesenchymal stem cells obtained under normal conditions with two different size syringes.Methods
Thirty adults (16 men and 14 women with a mean age of 49?±?14 years) underwent surgery with aspiration of bone marrow from their iliac crest. Bilateral aspirates were obtained from the iliac crest of the same patients with a 10-ml syringe and a 50-ml syringe. Cell analysis determined the frequencies of mesenchymal stem cells (as determined by the number of colonies) from each size of syringe. The cell count, progenitor cell concentration (colonies/ml marrow) and progenitor cell frequency (per million nucleated cells) were calculated. All bone marrow aspirates were harvested by the same surgeon.Results
Aspirates of bone marrow demonstrated greater concentrations of mesenchymal stem cells with a 10-ml syringe compared with matched controls using a 50-ml syringe. Progenitor cell concentrations were on average 300 % higher using a 10-ml syringe than matched controls using a 50-ml syringe (p?<?0.01).Conclusions
In normal human donors, bone marrow aspiration from 30 patients demonstrated a reduced mesenchymal stem cell number in aspirates obtained using a larger volume syringe (50 ml) as compared with a smaller volume syringe (10 ml). 相似文献79.
80.