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排序方式: 共有387条查询结果,搜索用时 390 毫秒
91.
Jamie McIntosh Godwin Dennison Jeff M. P. Holly Caroline Jarrett Alexandra Frankow Emily J. Foulstone Zoe E. Winters Claire M. Perks 《The Journal of biological chemistry》2010,285(50):38788-38800
Progression of breast cancer is associated with remodeling of the extracellular matrix, often involving a switch from estrogen dependence to a dependence on EGF receptor (EGFR)/HER-2 and is accompanied by increased expression of the main binding protein for insulin-like growth factors (IGFBP-3). We have examined the effects of IGFBP-3 on EGF responses of breast epithelial cells in the context of changes in the extracellular matrix. On plastic and laminin with MCF-10A normal breast epithelial cells, EGF and IGFBP-3 each increased cell growth and together produced a synergistic response, whereas with T47D breast cancer cells IGFBP-3 alone had no effect, but the ability of EGF to increase cell proliferation was markedly inhibited in the presence of IGFBP-3. In contrast on fibronectin with MCF-10A cells, IGFBP-3 alone inhibited cell growth and blocked EGF-induced proliferation. With the cancer cells, IGFBP-3 alone had no effect but enhanced the EGF-induced increase in cell growth. The insulin-like growth factor-independent effects of IGFBP-3 alone on cell proliferation were completely abrogated in the presence of an EGFR, tyrosine kinase inhibitor, Iressa. Although IGFBP-3 did not affect EGFR phosphorylation [Tyr1068], it was found to modulate receptor internalization and was associated with activation of Rho and subsequent changes in MAPK phosphorylation. The levels of fibronectin and IGFBP-3 within breast tumors may determine their dependence on EGFR and their response to therapies targeting this receptor. 相似文献
92.
93.
Christy A. Lotz Michael J. Agnew Alison A. Godwin Joan M. Stevenson 《Journal of electromyography and kinesiology》2009,19(2):331-340
Occupations demanding frequent and heavy lifting are associated with an increased risk of injury. A personal lift assist device (PLAD) was designed to assist human muscles through the use of elastic elements. This study was designed to determine if the PLAD could reduce the level of general and local back muscle fatigue during a cyclical lifting task. Electromyography of two erector spinae sites (T9 and L3) was recorded during a 45-min lifting session at six lifts/lowers per minute in which male participants (n = 10) lifted a box scaled to represent 20% of their maximum back extensor strength. The PLAD device reduced the severity of muscular fatigue at both muscle sites. RMS amplitude increased minimally (22% and 26%) compared to the no-PLAD condition (104% and 88%). Minimal median frequency decreases (0.33% and 0.41%) were observed in the PLAD condition compared to drops of 12% and 20% in the no-PLAD condition. The PLAD had an additional benefit of minimizing pre–post changes in muscular strength and endurance. The PLAD also resulted in a significantly lower rate of perceived exertion across the lifting session. It was concluded that the PLAD was effective at decreasing the level of back muscular fatigue. 相似文献
94.
Several members of the synaptotagmin (syt) family of vesicle proteins have been proposed to act as Ca2+ sensors on synaptic vesicles. The mechanism by which calcium activates this class of proteins has been the subject of controversy, yet relatively few detailed biophysical studies have been reported on how isoforms other than syt I respond to divalent metal ions. Here, we report a series of studies on the response of syt II to a wide range of metal ions. Analytical ultracentrifugation studies demonstrate that Ca2+ induces protein dimerization upon exposure to 5 mM Ca2+. Whereas Ba2+, Mg2+, or Sr2+ do not potentiate self-association as strongly as Ca2+, Pb2+ triggers self-association of syt II at concentrations as low as 10 microM. Partial proteolysis studies suggest that the various divalent metals cause different changes in the conformation of the protein. The high calcium concentrations required for self-association of syt II suggest that the oligomerized state of this protein is not a critical intermediate in vesicle fusion; however, low-affinity calcium sites on syt II may play a critical role in buffering calcium at the presynaptic active zone. In addition, the high propensity of lead to oligomerize syt II offers a possible molecular explanation for how lead interferes with calcium-evoked neurotransmitter release. 相似文献
95.
Accumulation of genetic and epigenetic aberrations leads to malignant transformation of normal cells. Functional studies of cancer using genomic and proteomic tools will help to reveal the true complexity of the processes leading to cancer development in humans. Until recently, diagnosis and prognosis of cancer was based on conventional pathologic criteria and epidemiological evidence. Certain tumors were divided only into relatively broad histological and morphological subcategories. Rapidly developing methods of differential gene expression analysis promote the search for clinically relevant genes changing their expression levels during malignant transformation. DNA microarrays offer a unique possibility to rapidly assess the global expression picture of thousands genes in any given time point and compare the detailed combinatory analysis results of global expression profiles for normal and malignant cells at various functional stages or separate experimental conditions. Acquisition of such "genetic portraits" allows searching for regularity and difference in expression patterns of certain genes, understanding their function and pathological importance, and ultimately developing the "molecular nosology" of cancer. This review describes the basis of DNA microarray technology and methodology, and focuses on their applications in molecular classification of tumors, drug sensitivity and resistance studies, and identification of biological markers of cancer. 相似文献
96.
Smedberg JL Smith ER Capo-Chichi CD Frolov A Yang DH Godwin AK Xu XX 《The Journal of biological chemistry》2002,277(43):40911-40918
The formation of extraembryonic endoderm is one of the earliest steps in the differentiation of pluripotent cells of the inner cell mass during the early stages of embryonic development. The primitive endoderm cells and the derived parietal and visceral endoderm cells gain the capacity to produce collagen IV and laminin. The deposition of these components results in the formation of basement membrane and epithelium of the endoderm, with polarized cells covering the inner surface of the blastocoels. We used retinoic acid-induced endoderm differentiation of stem cell-like F9 embryonic carcinoma cells to study the role of the Ras pathway and its regulation in the formation of the visceral endoderm. Upon endoderm differentiation of F9 cells induced by retinoic acid, c-Fos expression, the downstream target of the Ras pathway, is suppressed by uncoupling Elk-1 phosphorylation/activation to MAPK activity. However, attachment to matrix gel greatly enhances the activation of MAPK in endoderm cells but not in undifferentiated F9 cells. Enhanced MAPK activation as a result of contact with basement membrane is able to compensate for reduced Elk-1 phosphorylation and c-Fos expression. We conclude that endoderm differentiation renders the activation of the Ras pathway basement membrane dependent, contributing to the epithelial organization of the visceral endoderm. 相似文献
97.
98.
Joseph U. Igietseme Godwin A. Ananaba Debra H. Candal Deborah Lyn Carolyn M. Black 《Microbiology and immunology》1998,42(9):617-625
The antimicrobial activity of T cell-derived cytokines, especially interferon (IFN)-γ, against intracellular pathogens, such as Chlamydia trachomatis, involves the induction of 3 major biochemical processes: tryptophan catabolism, nitric oxide (NO) induction and intracellular iron (Fe) deprivation. Since the epithelial cell is the natural target of chlamydial infection, the presence of these antimicrobial systems in the cell would suggest that they may be involved in T cell control of intracellular multiplication of Chlamydia. However, the controversy over whether these 3 antimicrobial processes are present in both mice and humans has precluded the assessment of the relative contribution of each of the 3 mechanisms to chlamydial inhibition in the same epithelial cell from either mice or humans. In the present study, we identified a Chlamydia-susceptible human epithelial cell line, RT4, that possesses the 3 antimicrobial systems, and we examined the role of nitric oxide (NO) induction, and deprivation of tryptophan or Fe in cytokine-induced inhibition of chlamydiae. It was found that the 3 antimicrobial systems contributed to cytokine-mediated inhibition of the intracellular growth of Chlamydia. NO induction accounted for ~20% of the growth inhibition; tryptophan catabolism contributed approximately 30%; iron deprivation was least effective; but the combination of the 3 systems accounted for greater than 60% of the inhibition observed. These results indicate that immune control of chlamydial growth in human epithelial cells may involve multiple mechanisms that include NO induction, tryptophan catabolism and Fe deprivation. 相似文献
99.
1. The c.d. (circular dichroism) of Drosophila melanogaster rRNA (42% G+C) and of G+C-rich fragments (78% G+C) obtained by partial hydrolysis of rabbit L-rRNA (the largest RNA species isolated from the large subribosomal particle) were measured and found to differ substantially. 2. To interpret these spectra a relation between c.d. of bihelical RNA and % G+C was derived, namely delta epsilonfG = AFG2+bfG+c, where deltaepsilonfG is the c.d. of RNA characterized by a mole fraction, fG, of guanine nucleotides and a, b and c are constants. 3. A frame of reference was established by studying the c.d. of a range of rRNA species, including S-rRNA (the RNA species isolated from the smaller subribosomal particle) and L-rRNA of Escherichia coli. 4. It was found for the rRNA species studied that 0.60+/-0.05 of residues appear to form bihelical secondary structure. 5. A higher helical content, 0.66+/-0.05, was found for the G+C-rich fragment of L-rRNA. The difference in the c.d. of rabbit L-rRNA and of D. melanogaster rRNA is attributable to the dependence of c.d. of the bihelical parts on %G+C. 6. The minimum in c.d. at 295 nm increases with increasing %G+C. The c.d. of rRNA was compared with that of the parent subparticle in this region of the spectrum, where high precision may be attained. 相似文献
100.
The entomopathogensSerratia marcescens Bizio and nucleopolyhedrosis virus were each fed alone and in combination with the parasiteBlepharipa pratensis (Meigen) to 4th-instar gypsy moth,Lymantria dispar, (L.) larvae. At LD30 for NPV, the presence of the parasite enhanced polyhedrosis about 30%, but the total number of gypsy moth larvae and pupae killed (85%) was not significantly different from the number killed by the parasite alone (93%). When the parasite was combined withS. marcencens, a strain nonpathogenic inL. dispar, total mortality was not significantly different from that in insects exposed only to the parasite (89 and 86%, respectively), but parasite survival was reduced about 12%. However, deaths not attributable to the parasite could not be ascribed to the bacterium either. 相似文献