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41.
Increased production of gelatinase B (matrix metalloproteinase-9) and interleukin-6 by activated rat microglia in culture 总被引:1,自引:0,他引:1
Activated macrophages produce several matrix metalloproteinases (MMPs), a family of extracellular matrix (ECM)-degrading enzymes, during wound healing and in other inflammatory states. In response to brain injury, brain microglia become "activated," in a way similar to peripheral tissue macrophages, a process which includes differentiation and probably invasion and proliferation. Little is known about the ECM-degrading MMPs that are secreted by microglia upon activation. Thus, it was of interest to determine whether activated microglia secrete MMPs. Conditioned media samples obtained from cultured microglia that were stimulated with various activating agents were subjected to gelatin-substrate zymography. Microglia constitutively express low levels of a 94-kDa gelatinase (GLase) activity. Treatment with LPS, zymosan, and fixed Staphylococcus aureus for 24 hr stimulated the activity of the 94-kDa GLase, 4-20-fold, in a dose-dependent manner. Addition of INF gamma inhibited the LPS-stimulated activity of MMP-9. LPS, zymosan, and fixed Staphylococcus aureus also stimulated the secretion of IL-6 from microglia in a dose-dependent manner. The 94-kDa GLase activity was Ca++ dependent, it was inhibited by 1,10-phenanthroline, and it was activated by organomercurial compounds. When immunoblots were performed using specific antisera against the 94-kDa gelatinase B (MMP-9) with untreated and LPS-stimulated conditioned medium samples, a 94-kDa immunopositive band was observed. Thus, it appears that the 94-kDa GLase is gelatinase B (MMP-9). These results indicate that activators of peripheral macrophages are potent secretagogues for the MMPs in cultured microglia. The ability of activated microglia to secrete MMPs suggests that these enzymes may play an important function in the brain parenchyma during inflammatory states. 相似文献
42.
Emotion regulation has been conceptualized as the extrinsic and intrinsic processes responsible for monitoring, facilitating, and inhibiting heightened levels of positive and negative affect. Regulation of distress is related to the use of certain behavioral strategies. Our study examined whether putative regulatory behaviors widely assumed to be conceptually associated with these strategies are actually empirically associated with the changes in fearful and angry distress in 6-, 12-, and 18-month-old infants. Our key finding was that the use of some putative regulatory behaviors (e.g., distraction and approach) reduced the observable intensity of anger but were less effective in reducing the intensity of fear. The results suggest (1) caution in assuming that postulated regulatory behaviors actually have general distress-reducing effects and (2) the likelihood that "distress" is too global a construct for research on emotion regulation. 相似文献
43.
PURPOSE: Previous studies of monochromatic visual evoked potentials confirm the strong suppression of (the cortical representation of) paracentral retinal areas of functionally amblyopic eyes, by a flat response to a blue stimulus. A clinical trial stimulating these areas with blue light was encouraging, and justified a prospective comparison of this treatment with conventional classic treatment. SUBJECTS AND METHODS: In 50 strabismic children with amblyopia, the blue filter treatment protocol (flash stimulation with, and the wearing of, a blue filter during occlusion of the better eye for one hour daily) was compared with the classical treatment (full time total occlusion by patch) in a prospective matched and randomized study. Patients 3 to 7 years old without previous treatment and a visual acuity up to 0.3 were admitted to the study. Visual acuity and fixation behavior were used as the parameters of comparison. Visual Evoked Potentials by monochromatic flashes were also studied. Results of treatment were compared after 6 months. RESULTS: The visual acuity outcome for the blue filter treatment was "statistically significantly" better (p=0.005). The greatest improvement was seen in the subgroup of children with eccentric fixation (p=0.01). Fixation behavior also showed a better outcome from the blue filter treatment (p=0.05) favoring especially children between 3 and 5 years. In children of this age with a visual acuity better than 0.1 we found a very "statistically significant" difference between the two treatments (p=0.004). In children 3 to 5 years old with poorer visual acuity we also found a "statistically significant" difference in the two treatments (p=0.04). The interocular difference of amplitude on the Visual Evoked Potentials also demonstrated more improvement in children treated with the blue filter. This treatment improved especially the cortical response to blue flash stimulation, correlating to paracentral retinal areas. CONCLUSIONS: The blue filter treatment protocol provided better results for treating amblyopia than the conventional classic occlusion treatment method. We propose that stimulation of these paracentral retinal areas triggers a better disinhibition of a functionally amblyopic eye. 相似文献
44.
The mu-opioid receptor (mu-OR), like most G-protein-coupled receptors, is rapidly internalized after agonist binding. Although opioid peptides induce internalization in vivo, there are no studies that demonstrate mu-OR internalization in response to natural stimuli. In this study, we used laser-scanning microscopy to demonstrate that estrogen treatment induces the translocation of mu-OR immunoreactivity (mu-ORi) from the membrane to an internal location in steroid-sensitive cell groups of the limbic system and hypothalamus. Estrogen-induced internalization was prevented by the opioid antagonist naltrexone, suggesting that translocation was largely dependent on release of endogenous agonists. Estrogen treatment also altered the pattern of mu-ORi at the bright-field light microscopic level. In the absence of stimulation, the majority of immunoreactivity is diffuse, with few definable mu-OR+ cell bodies or processes. After stimulation, the density of distinct processes filled with mu-ORi was significantly increased. We interpreted the increase in the number of mu-OR+ processes as indicating increased levels of internalization. Using this increase in the density of mu-OR+ fibers, we showed that treatment of ovariectomized rats with estradiol benzoate induced a rapid and reversible increase in the number of fibers. Significant internalization was noted within 30 min and lasted for >24 hr after estrogen treatment in the medial preoptic nucleus, the principal part of the bed nucleus, and the posterodorsal medial amygdala. Naltrexone prevented the increase of mu-OR+ processes. These data imply that estrogen treatment stimulates the release of endogenous opioids that activate mu-OR in the limbic system and hypothalamus providing a "neurochemical signature" of steroid activation of these circuits. 相似文献
45.
Covariance structures analysis is often used in nursing research to appraise statistical models reflecting complex human health processes. The model selection approach in covariance structures analysis is designed to select the "best" model from a specified set of theoretically defensible, competing alternatives, all of which are viewed as approximations. Model selection criteria explicitly incorporate both model misfit in the population and sampling error to evaluate the set of models. The result is that interpretability of model parameters and goodness-of-fit are enhanced simultaneously. Relative merits of the model selection approach are identified in light of technical concerns, parsimony, and use of scientific theory in nursing. 相似文献
46.
Cardiac transplantation in perspective for the future. Survival, complications, rehabilitation, and cost 总被引:1,自引:0,他引:1
JL Pennock PE Oyer BA Reitz SW Jamieson CP Bieber J Wallwork EB Stinson NE Shumway 《Canadian Metallurgical Quarterly》1982,83(2):168-177
Two hundred twenty-seven cardiac transplant procedures have been performed in 206 patients from January, 1968, to April, 1981. Postoperative survival rates, calculated by the actuarial method for program years 1968 to 1973 (66 patients), are 44%, 33%, 27%, 21%, and 18% at 1, 2, 3, 4, and 5 years after transplantation, respectively. Postoperative survival rates for program years 1974 to 1981 (140 patients) are 63%, 55%, 51, 44%, and 39% at 1, 2, 3, 4, and 5 years after transplantation, respectively. This increase results primarily from improvement in survival achieved in the first 3 postoperative months (59% +/- 7%, 1968 to 1973, versus 80% +/- 40%, 1974 to 1980), reflecting improved patient management. Infection remains the primary cause of death following transplantation (76/131 patients, 58%), followed by acute rejection (24/181, 18.3%), graft arteriosclerosis (14/131, 10.7%), and malignancy (6/131, 4.6%). The development of graft arteriosclerosis has been examined in 85 one-year survivors studied by annual coronary arteriograms. Coronary lesions of varying severity have developed in 21 patients. HLA-A2 incompatibility was associated with a higher incidence of graft arteriosclerosis than was apparent for all other A locus incompatibilities (p less than 0.0003). Lymphoma has been shown to be associated with younger recipient age, a primary disease diagnosis of idiopathic cardiomyopathy, and retransplantation. One hundred six patients have survived at least 1 year after transplantation; 97% were in NYHA Class 1 at that time interval and 82% returned to employment or activity of choice. The longest survival time is new 11 years, 3 months. Cardiac transplantation can be considered "reasonable and therapeutic treatment to extend life" in selected individuals. 相似文献
47.
The roles chronological age and gender play in subjective time experience were explored in a sample of 294 adult men and women. Subjective time experience (STE: the difference between subjective age and chronological age) was found to vary widely among individuals, with some being "accurate" (SA = CA), and others either "retarded" (SA less than CA) or "advanced" (SA greater than CA). Males were more retarded in STE than females at every point in the lifespan, and patterns of age differences in adulthood differed for the two sexes as well. The results suggest that chronological age may play a key role in transitions in STE, and that chronological age is more significant in the STE of women than in the STE of men. 相似文献
48.
The paper deals with an experimental determination of the stretch zone dimensions in the notch tip in thin steel sheets. The stretch zone dimensions depend on steel grade, on the rolling direction as well as on the loading rate. Stretch zones were observed and measured on three steel grades. Fracture area and stretch zones were analysed by SEM. Stable crack growth was monitored by videoextensometry techniques on CT (Compact Tension) specimens. Specimens were loaded under two loading rates by eccentric tension, whereby the deformation in the notch surrounding area was recorded using a non-contact measurement–videoextensometry technique. Linear relation between the stretch zone dimensions was determined. 相似文献
49.
50.
Jurkat T cells undergo rapid apoptosis upon stimulation of the Fas/APO-1 (CD95) receptor. We examined the role of the mitogen-activated protein kinase (MAPK) cascade as a negative regulator of Fas-mediated apoptosis. To this end, we used both physiologic and artificial activators of MAPK, all of which activate MAPK by distinct routes. MAPK activity could be efficiently elevated by two T cell mitogens, the lectin PHA and an agonistic Ab to the T cell receptor complex as well as by the type 1 and 2A phosphatase inhibitor, calyculin A, and the protein kinase C-activating phorbol ester, tetradecanoyl phorbol acetate. All these treatments were effective in preventing the characteristic early and late features of Fas-mediated apoptosis, including activation of caspases. Our results indicate that the elevated MAPK activities intervene upstream of caspase activation. The degree of MAPK activation by the different stimuli used in our study corresponds well to their potency to inhibit apoptosis, indicating that MAPK activation serves as an efficient modulator of Fas-mediated apoptosis. The role of MAPK in modulation of Fas-mediated apoptosis was further corroborated by transient transfection with constitutively active MAPK kinase, resulting in complete inhibition of the Fas response, whereas transfection with a dominant negative form of MAPK kinase had no effect. Furthermore, the apoptosis inhibitory effect of the MAPK activators could be abolished by the specific MAPK kinase inhibitor PD 098059. Modulation of Fas responses by MAPK signaling may determine the persistence of an immune response and may explain the insensitivity of recently activated T cells to Fas receptor stimulation. 相似文献