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71.
Platelet-derived growth factor activates mitogen-activated protein kinase in isolated caveolae 总被引:2,自引:0,他引:2
The ability of a peptide hormone to affect many different intracellular targets is thought to be possible because of the modular organization of signal transducing molecules in the cell. Evidence for the presence of signaling modules in metazoan cells, however, is incomplete. Herein we show, with morphology and cell fractionation, that all the components of a mitogen-activated protein kinase pathway are concentrated in caveolae of unstimulated human fibroblasts. Addition of platelet-derived growth factor to either the intact cell or caveolae isolated from these cells stimulates tyrosine phosphorylation and activates mitogen-activated protein kinases in caveolae. The molecular machinery for kinase activation, therefore, is preorganized at the cell surface of quiescent cells. 相似文献
72.
LK Bachrach K N?nto-Salonen P Tapanainen RG Rosenfeld SE Gargosky 《Canadian Metallurgical Quarterly》1995,5(2):109-118
OBJECTIVE: The study investigated the value of using national or regional data bases to examine care in a specific hospital. DATA SOURCES: The following data sources were included: (1) the results of the 1992 HCFA analysis of the index hospital for patients hospitalized in fiscal year 1990; (2) the 1989 Medicare Provider Analysis and Review (MEDPAR) file; and (3) clinical information from bypass surgery patients in Wisconsin and from the index hospital. PRINCIPAL FINDINGS: The assessment of the mortality rates in the index hospital for all conditions combined and for CABG patients differed depending on what data base was used and how the data were analysed. The national data were most useful in establishing that the coding practices for all patients and the mortality rate for intra-aortic balloon patients differed between the index hospital and other hospitals. The regional clinical data base for bypass surgery patients was used to establish that the high mortality rates for intra-aortic balloon patients were due to patient selection. CONCLUSIONS: National claims data must be analysed carefully before applying results to an individual hospital. Even a careful analysis is more for raising questions about care at a specific hospital rather than for reaching definitive conclusions. 相似文献
73.
DB Fram TA Aretz JF Mikan A Raisner JF Mitchel LD Gillam DD Waters RG McKay 《Canadian Metallurgical Quarterly》1993,126(4):969-978
The purpose of this study was to assess the safety and histologic effects of radiofrequency thermal balloon angioplasty in the coronary vasculature of normal pigs. Radiofrequency thermal balloon angioplasty was performed in 30 coronary arteries of 16 nonatherosclerotic pigs. Heated inflations were performed at either 50 degrees, 60 degrees, or 70 degrees C for 30 or 60 seconds, and were compared with five nonheated inflations in five additional arteries. All balloon inflations were performed at 2 atm pressure with a balloon/vessel diameter ratio of 1.2 to 1. Heart rate, arterial pressure, and left ventricular pressure were monitored continuously for each animal. A 12-lead ECG, coronary angiography, and two-dimensional transthoracic echocardiography were performed before and 1 hour after each balloon inflation. Each animal was subsequently put to death for postmortem cardiac examination. Heated inflations were well tolerated in 28 of the 30 arteries without significant adverse effects. During one inflation, ventricular fibrillation occurred because of prolonged ischemia from an occlusive guiding catheter. In another artery, a heated inflation resulted in a dissection with a transient decrease in distal coronary flow. Histologic examination revealed a significant increase in wall thinning and elastic fiber straightening with heating at 70 degrees C for both 30 and 60 seconds, and a significant increase in intracoronary thrombus with heating at 70 degrees C for 60 seconds. Depth of periarterial myocardial heat necrosis paralleled the increase in temperature, with an average depth of 166 microns at 50 degrees C, 312 microns at 60 degrees C, and 1031 microns at 70 degrees C. In vivo, radiofrequency coronary angioplasty can be performed relatively safely without significant electrical, hemodynamic, or ischemic changes beyond those seen with conventional nonthermal angioplasty. The extent of heat-induced vessel wall thinning, elastic tissue straightening, intracoronary thrombus formation, and periarterial myocardial necrosis are all related to balloon temperature or duration of heating. 相似文献
74.
Amphibian populations appear to be declining around the world. Although there is no single cause, one factor may be pollution from heavy metals. As a result of mining in the Silver Valley of Idaho, heavy metals have been released into habitats containing many species of sensitive organisms, including spotted frogs (Rana luteiventris). While the gross extent of pollution has been well documented, the more subtle behavioral effects of heavy metals such as lead, zinc, and cadmium are less well studied. We tested the effects of heavy metals on the short-term survival (LC50) of spotted frog tadpoles. Compared to single metals, metals presented together were toxic at lower doses. We also raised the tadpoles in outdoor mini-ecosystems containing either a single heavy metal or soil from an EPA Superfund site in the Silver Valley known to be composed of numerous heavy metals. Exposure to Silver Valley soil resulted in delayed metamorphosis. We tested the ability of metal-exposed tadpoles to detect and respond to chemical cues emanating from predacious rainbow trout. We found that high levels of Silver Valley soil, medium levels of zinc, and medium and high levels of lead resulted in a decreased fright response. Low levels of cadmium, zinc, and lead did not cause a significant effect, but low levels of soil did result in a decreased fright response. Heavy metals may alter interactions between tadpoles and their predators. 相似文献
75.
BACKGROUND: Synthetic homopyrimidine peptide nucleic acids (PNAs) can bind complementary targets in double-stranded DNA, generating strand-displacement complexes, and so offering an opportunity to modulate specific gene expression. Several issues remain to be addressed before these attributes can be exploited in vivo, however. RESULTS: The kinetics of the interaction between a homopyrimidine PNA and a complementary homopurine target on double-stranded DNA were analyzed in the presence or absence of a preformed strand-displacement complex proximal to the target. The complex was established under low salt conditions by the binding of a different homopyrimidine PNA to a target situated adjacent to the first PNA target. These two targets were placed next to each other on opposite strands at distances of 0, 2, 4 and 8 base pairs apart. The presence of a preformed strand-displacement complex near the target accelerates the binding of PNA to double-stranded DNA in a salt-dependent manner. The influence of salt on the binding rates was also examined. The binding rate is increased by a factor of 1 x exp(70[NaCl]), that is, 16-fold at 40 mM NaCl and more than 10(4)-fold if extrapolated to 140 mM NaCl. This effect is significantly reduced if the two targets are 2 base pairs apart and completely absent if the distance is 4 base pairs or more. CONCLUSIONS: The perturbation of the DNA helix imposed by a PNA strand-displacement complex only propagates a few base pairs. It is therefore possible to target sites in the immediate vicinity of strand invasion complexes specifically. The results presented have implications for the mechanism of strand displacement and for the application of PNA in a genomic context. 相似文献
76.
J Pizarro-Cerdá S Méresse RG Parton G van der Goot A Sola-Landa I Lopez-Go?i E Moreno JP Gorvel 《Canadian Metallurgical Quarterly》1998,66(12):5711-5724
Brucella abortus is an intracellular pathogen that replicates within a membrane-bounded compartment. In this study, we have examined the intracellular pathway of the virulent B. abortus strain 2308 (S2308) and the attenuated strain 19 (S19) in HeLa cells. At 10 min after inoculation, both bacterial strains are transiently detected in phagosomes characterized by the presence of early endosomal markers such as the early endosomal antigen 1. At approximately 1 h postinoculation, bacteria are located within a compartment positive for the lysosome-associated membrane proteins (LAMPs) and the endoplasmic reticulum (ER) marker sec61beta but negative for the mannose 6-phosphate receptors and cathepsin D. Interestingly, this compartment is also positive for the autophagosomal marker monodansylcadaverin, suggesting that S2308 and S19 are located in autophagic vacuoles. At 24 h after inoculation, attenuated S19 is degraded in lysosomes, while virulent S2308 multiplies within a LAMP- and cathepsin D-negative but sec61beta- and protein disulfide isomerase-positive compartment. Furthermore, treatment of infected cells with the pore-forming toxin aerolysin from Aeromonas hydrophila causes vacuolation of the bacterial replication compartment. These results are compatible with the hypothesis that pathogenic B. abortus exploits the autophagic machinery of HeLa cells to establish an intracellular niche favorable for its replication within the ER. 相似文献
77.
We describe an 8-year-old boy who had asymptomatic hypercalcemia 4 years after radiotherapy involving the left orbit and lungs. A right parathyroid adenoma was diagnosed, and normocalcemia was achieved after its removal. Routine monitoring of serum calcium and phosphate levels is recommended for children after head and neck irradiation. 相似文献
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