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Hepatic gene downregulation following acute and subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. 总被引:1,自引:0,他引:1
Bladimir J Ovando Chad M Vezina Barbara P McGarrigle James R Olson 《Toxicological sciences》2006,94(2):428-438
Chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to lead to the development of hepatotoxicity and carcinogenicity in the liver of female rats. In this study, we investigated hepatic gene downregulation in response to acute and subchronic TCDD exposure. We identified 61 probes which exhibited a downregulation of twofold or greater following subchronic (13 weeks) exposure to TCDD. Comparative analysis of the hepatic expression of these 61 probes was conducted with rats subchronically exposed to PeCDF, PCB126, PCB153, and a mixture of PCB126 and PCB153. PCB153 produced little or no alteration in these probes, while the binary mixture mimicked most closely the downregulation observed with TCDD. To discern if the repression of genes within this probe set occur as a primary response to TCDD exposure, we analyzed the early responsiveness of 11 genes at 6, 24, and 72 h following a single exposure to TCDD. We observed early repression of the 11 genes within this early time course, indicating that the repression of this subset of genes occurs as a primary response to TCDD exposure and not as a secondary response to 13 weeks of subchronic treatment. In addition, the gender, species, and AhR dependence of these responses were also investigated. Gender- and species-dependent repression was observed within this subset of genes. Furthermore, utilizing AhR knockout mice, we were able to determine the AhR-dependent downregulation of seven of 11 genes. Together these results assist efforts to understand the multitude of effects imposed by TCDD and AhR ligands on gene expression. 相似文献
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Marilyn Sawyer Sommers 《Journal of nursing scholarship》2006,38(4):314-320
PURPOSE: To discuss injury research as a phenomenon of concern in nursing science. ORGANIZING CONSTRUCT: Injury is defined as the physical damage that results when the human body is briefly subjected to intolerable levels of energy. It is the leading cause of death in the first 4 decades of life in high-income nations and is second only to infectious diseases as a leading cause of death in low- and middle-income nations. METHODS: Review and discussion of relevant scientific and theoretical literature in both injury and nursing science. FINDINGS: Nurse scientists can apply unique perspectives to increase understanding of injury and its consequences. Fertile areas for nursing inquiry include identifying people at risk, developing models to explain the association between risk-taking and injury, testing interventions to prevent and limit injury, and creating and refining interventions that are culturally relevant to subpopulations most at risk for injury. CONCLUSIONS: The mandate to improve global heath should lead to nursing inquiry about this phenomenon, including developing and testing interventions to prevent and reduce injury. 相似文献
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This article describes the proceedings of the 2006 Annual Meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG), which was held in Baltimore, Maryland on June 24, 2006. The meeting was held in conjunction with the annual meeting of the Research Society on Alcoholism and was supported by a grant from the National Institute on Alcohol Abuse and Alcoholism. The 2005-2006 FASDSG officers, Daniel J. Bonthius (President), Heather Carmichael Olson (Vice-President), and Jennifer Thomas (Secretary-Treasurer), organized the meeting. Nationally prominent speakers delivered plenary lectures on topics of newborn screening, ethics, and neuroscience. Selected members of the FASDSG provided brief scientific data (FASt) reports, describing new research findings. Representatives from national agencies involved in fetal alcohol syndrome (FAS) research, treatment, and prevention provided updates regarding priorities, funding, and agency activities. Presentations were also made by the 2006 Student Merit Award recipient and by the 2006 Rosett Award recipient. The meeting served as a forum for clinicians, neuroscientists, psychologists, social scientists, and other professionals to discuss recent advances in FAS research and to identify the most important gaps in the understanding of alcohol-induced teratology. 相似文献
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B Djuricic S R Olson H M Assaf T S Whittingham W D Lust L R Drewes 《Journal of cerebral blood flow and metabolism》1991,11(2):308-313
Free choline and ATP contents were measured in Mongolian gerbil hippocampal slices (tissue) and incubation media (media) during exposure to 30 min of aglycemia, high potassium, anoxia, or ischemia. Changes in choline levels reflected the degree of energy reduction, lower ATP levels being associated with high choline (4-fold increase during exposure to high potassium and anoxia, and 11-fold increase during ischemia). Media (extracellular) choline was particularly affected and increased about twofold during relatively mild energy depletion (e.g., aglycemia), but tissue choline content was less sensitive to energy reduction. A plot of choline vs. ATP levels indicated a nonlinear correlation, and the sharp increase in choline occurred when ATP values fell to about 2.5 nmol/mg of protein. Inhibition of acetylcholine sterase by 10 microM physostigmine during ischemia did not prevent an increase in choline contents but rather enhanced them, indicating that acetylcholine hydrolysis was not the source of free choline. Formation of free choline was Ca2+ independent. These findings suggest the involvement of phospholipase D and phosphatidylcholine hydrolysis in free choline formation during energy stress. The extent of choline formation may be an indicator of the degree of membranal damage, which in turn reflects damage to the metabolic machinery of the cell. 相似文献
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D G Scholz J M Olson D L Thurber D E Larson 《Mayo Clinic proceedings. Mayo Clinic》1989,64(3):335-338
A 53-year-old woman was examined at our medical center because of progressive dysphagia of 14 days' duration and a severe inability to open her mouth and swallow saliva. A barium esophagogram showed no obstruction, but pooling of barium in the hypopharynx suggested a neuromuscular disorder. The clinical diagnosis of tetanus was confirmed by electromyography. With appropriate therapy, the patient recovered during a period of 6 weeks. This case illustrates both an uncommon cause of dysphagia and an uncommon initial manifestation of tetanus. 相似文献
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In the first 100 patients operated on for C T-E PH, three were referred with the diagnosis of UPAA having been made elsewhere. We found that many features of these two conditions are so similar that differential diagnosis is very difficult. Shared features may include findings on chest x-ray film, pulmonary angiography, CT scan and MRI studies. Since the two conditions vary substantially with respect to the methods of potential surgical correction, recognition of this possible differential diagnostic dilemma is important. 相似文献