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51.
The use of 7-amino actinomycin D in identifying apoptosis: simplicity of use and broad spectrum of application compared with other techniques 总被引:9,自引:5,他引:9
Philpott NJ; Turner AJ; Scopes J; Westby M; Marsh JC; Gordon-Smith EC; Dalgleish AG; Gibson FM 《Blood》1996,87(6):2244-2251
The detection and quantitation of apoptotic cells is becoming increasingly important in the investigation of the role of apoptosis in cellular proliferation and differentiation. The pathogenesis of hematologic disorders such as aplastic anemia and the development of neoplasia are believed to involve dysregulation of apoptosis. To quantitate accurately the proportion of apoptosis cells within different cell types of a heterogeneous cell population such as blood or bone marrow, a method is required that combines the analysis of large numbers of cells with concurrent immunophenotyping of cell surface antigens. In this study, we have evaluated such a method using the fluorescent DNA binding agent, 7-amino actinomycin D (7AAD), to stain three diverse human cell lines, induced to undergo apoptosis by three different stimuli. Flow cytometric analysis defines three populations on the basis of 7AAD fluorescence and forward light scatter. We have shown by cell sorting and subsequent morphological assessment and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling that the populations defined by 7AAD represent live, apoptotic, and late-apoptotic/dead cells. This method is quick, simple, reproducible, and cheap and will be a valuable tool in the investigation of the role of apoptosis in normal physiology and in disease states. 相似文献
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Shiwen Peng Cornelia Trimble Lee Wu Drew Pardoll Richard Roden Chien-Fu Hung T-C Wu 《Clinical cancer research》2007,13(8):2479-2487
PURPOSE: The fact that up to 30% of established high-grade squamous intraepithelial lesions (HSIL) of the cervix regress spontaneously presents the opportunity to identify clinically relevant human papillomavirus (HPV) viral epitopes associated with disease outcome. Two human HPV antigens, E6 and E7, are functionally required for initiation and maintenance of cervical cancer precursor lesions and invasive cervical cancer. The identification and characterization of endogenously processed HPV antigenic epitopes in closely characterized patient cohorts will provide insight into the reasons for success or failure of therapeutic approaches. EXPERIMENTAL DESIGN: We characterized the HPV-16 E6/E7-specific T-cell epitopes using E6/E7 overlapping peptide pools with peripheral blood lymphocytes obtained from normal healthy donors. We then analyzed the difference in the HPV-16 T-cell immune responses in HPV-16+ HSIL patients with or without spontaneous regression of lesions using the statistical methods. RESULTS: We have identified an HPV-16 E7-specific CD4+ T-cell epitope [amino acids (aa) 71-85] that was restricted by HLA-DQB1*0201. Analysis of peripheral blood lymphocytes obtained from 14 HLA-DQB1*02 patients with HPV-16+ HSILs showed that the HPV-16+ E7 peptide (aa 71-85)-specific CD4+ T-cell immune response was significantly higher in the group of patients with regression compared with the patients without regression (P value <0.05). CONCLUSIONS: The HPV-16 E7 peptide-specific CD4+ T-cell immune response correlates with spontaneous regression of established HPV16+ HSILs. Thus, this E7 epitope may be useful for the characterization of HPV-specific immune responses in patients infected with HPV-16 or immunized with HPV vaccines. 相似文献
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Stewart BA Mohtashami M Trimble WS Boulianne GL 《Proceedings of the National Academy of Sciences of the United States of America》2000,97(25):13955-13960
A hallmark of calcium-triggered synaptic transmission is the cooperative relationship between calcium and the amount of transmitter released. This relationship is thought to be important for improving the efficiency of synaptic vesicle exocytosis. Although it is generally held that cooperativity arises from the interaction of multiple calcium ions with a single calcium-sensing molecule, the precise molecular basis of this phenomenon is not known. The SNARE proteins are known to be critical for synaptic vesicle exocytosis. We therefore tested for a contribution of SNARE proteins to cooperativity by genetically reducing the levels of syntaxin IA and neuronal-synaptobrevin in Drosophila. Surprisingly, we found that reducing these SNARE proteins also reduced Ca(2+) cooperativity. Thus, SNARE proteins are important for determining the cooperative relationship between calcium and synaptic transmission. 相似文献
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The role of hippocampal sclerosis in topiramate-related depression and cognitive deficits in people with epilepsy 总被引:7,自引:1,他引:6
PURPOSE: To clarify the role of hippocampal sclerosis (HS) in developing psychiatric and cognitive adverse events during therapy with topiramate (TPM) in patients with temporal lobe epilepsy (TLE). METHODS: We analyzed the data of 70 patients with TLE and HS and 128 patients with cryptogenic TLE matched for age, sex, starting dose, and titration schedule of TPM. They were selected from the first consecutive 431 patients started on TPM between 1995 and 1999. RESULTS: Patients with HS were more likely to develop cognitive adverse events (CAEs; p = 0.002) and depression (p = 0.018) and to be receiving a polytherapy regimen (p = 0.007). However, regression analysis demonstrated that only HS was a predictive factor for the occurrence of CAEs (OR = 2.4; p < 0.001) and depression (OR = 2.3; p = 0.02). CONCLUSIONS: Patients with TLE and HS were more prone to develop CAEs and depression than were patients with cryptogenic TLE, during TPM therapy, despite the same titration schedule. The presence of HS and not duration of epilepsy or polytherapy regimen represented the main risk factor. 相似文献
57.
Glucose-induced oxidative stress in mesangial cells 总被引:24,自引:0,他引:24
Catherwood MA Powell LA Anderson P McMaster D Sharpe PC Trimble ER 《Kidney international》2002,61(2):599-608
BACKGROUND: Hyperglycemia is a well-recognized pathogenic factor of long-term complications in diabetes mellitus. Hyperglycemia not only generates reactive oxygen species but also attenuates antioxidant mechanisms creating a state of oxidative stress. METHODS: Porcine mesangial cells were cultured in high glucose (HG) for ten days to investigate the effects on the antioxidant defenses of the cell. RESULTS: Mesangial cells cultured in HG conditions had significantly reduced levels of glutathione (GSH) compared with those grown in normal glucose (NG). The reduced GSH levels were accompanied by decreased gene expression of both subunits of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme in de novo synthesis of GSH. Elevated levels of intracellular malondialdehyde (MDA) were found in cells exposed to HG conditions. HG also caused elevated mRNA levels of the antioxidant enzymes CuZn superoxide dismutase (SOD) and MnSOD. These changes were accompanied by increased mRNA levels of extracellular matrix proteins (ECM), fibronectin (FN) and collagen IV (CIV). Addition of antioxidants to high glucose caused a significant reversal of FN and CIV gene expression; alpha-lipoic acid also up-regulated gamma-GCS gene expression and restored intracellular GSH and MDA levels. CONCLUSIONS: The results demonstrate the existence of glucose-induced oxidative stress in mesangial cells as evidenced by elevated MDA and decreased GSH levels. The decreased levels of GSH are as a result of decreased mRNA expression of gamma-GCS within the cell. Antioxidants caused a significant reversal of FN and CIV gene expression, suggesting an etiological link between oxidative stress and increased ECM protein synthesis. 相似文献
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Expression of Nedd5, A Mammalian Septin,in Human Brain Tumors 总被引:2,自引:0,他引:2
Sakai K Kurimoto M Tsugu A Hubbard SL Trimble WS Rutka JT 《Journal of neuro-oncology》2002,57(3):169-177