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91.
A great deal is now known about the mechanisms of conditioned fear acquisition and expression. More recently, the mechanisms
of inhibition of conditioned fear have become the subject of intensive study. The major model system for the study of fear
inhibition in the laboratory is extinction, in which a previously fear conditioned organism is exposed repeatedly to the fear-eliciting
cue in the absence of any aversive event and the fear conditioned response declines. It is well established that extinction
is a form of new learning as opposed to forgetting or “unlearning” of conditioned fear, and it is hypothesized that extinction
develops when sensory pathways conveying sensory information to the amygdala come to engage GABAergic interneurons through
forms of experience-dependent plasticity such as long-term potentiation. Several laboratories currently are investigating
methods of facilitating fear extinction in animals with the hope that such treatments might ultimately prove to be useful
in facilitating exposure-based therapy for anxiety disorders in clinical populations. This review discusses the advances that
have been made in this field and presents the findings of the first major clinical study to examine the therapeutic utility
of a drug that facilitates extinction in animals. It is concluded that extinction is an excellent model system for the study
of fear inhibition and an indispensable tool for the screening of putative pharmacotherapies for clinical use. 相似文献
92.
Brendan M McGuire Herbert L Bonkovsky Robert L Carithers Raymond T Chung Leonard I Goldstein John R Lake Anna S Lok Carol J Potter Elizabeth Rand Michael D Voigt Pamela R Davis Joseph R Bloomer 《Liver transplantation》2005,11(12):1590-1596
In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival. 相似文献
93.
Previous studies have shown that the decreased neutrophil migratory responsiveness seen in burned patients correlates with the extent of thermal injury and the extent of the neutrophil-specific granule deficiency. To understand better the relationship between the neutrophil dysfunction, degranulation, and thermal injury, a rabbit model was studied. Eighteen rabbits were burned over 20% of their surface area. Assay of peripheral blood heterophils disclosed decreased migratory activity compared with preburn levels and decreased lysozyme content vs preburn levels, but no change in the beta-glucuronidase content. The specific binding of tritiated formyl-methionyl-leucyl-phenylalanine to peripheral blood heterophils was increased fivefold over that of control cells. These studies indicate that, following thermal injury, there is a selective decrease of specific granule contents and an increase in chemoattractant binding to the cell and also suggest an abnormality in chemoattractant receptor processing. The rabbit provides a convenient model for the study of compromised host defenses following thermal injury. 相似文献
94.
J M Davis A Chadburn J A Mouradian 《Archives of surgery (Chicago, Ill. : 1960)》1988,123(11):1349-1352
Twenty-one male homosexuals were followed up by repeated lymph node biopsy for a mean (+/- SEM) follow-up of 99 +/- 18 weeks. Four histologic patterns were seen on biopsy: explosive follicular hyperplasia (EFH), follicular involution (FI), a mixed pattern of EFH with FI in the same node, and lymphocyte depletion. Patients with FI and lymphocyte depletion had mean survival times that were significantly less than those for the subjects with EFH. The percentage of lymph node follicles with suppressor cell clusters (T8) in EFH lymph nodes was significantly higher (43% vs 8%) than in nodes from patients without risk for human immunodeficiency virus infection. Helper/suppressor T-cell ratios in control nodes were 1.6; in EFH nodes, 0.97; and in FI nodes, 0.88. A remarkable 33% of patients in this lymphadenopathy group ultimately developed large-cell (B-cell) lymphoma, suggesting that the follicular stimulation noted histologically played a role in the development of this neoplasm. These data show that there is a progressive destruction of lymph node follicles that correlates with the progression of the disease and that lymph node histologic features may provide important prognostic information. 相似文献
95.
96.
Jonathan S. Jahr Fedor Lurie Bernd Driessen Jessica A. Davis Robert Gosselin Robert A. Gunther 《Journal canadien d'anesthésie》2002,49(3):243-248
PURPOSE: Accuracy of measurement of low hemoglobin concentrations using the HemoCue, a B-hemoglobin photometer (HemoCue AB, Angelholm, Sweden) may exhibit significant variability. Infusion of hemoglobin-based oxygen carriers (HBOC) results in low concentrations of plasma hemoglobin. Our study assessed B-hemoglobin photometer measurement accuracy of three HBOC: (hemoglobin glutamer-200 (bovine; Oxyglobin, Biopure Corp., Cambridge, MA, USA); hemoglobin glutamer-250 (bovine; Hemopure, Biopure Corp, Cambridge, MA, USA), and hemoglobin-raffimer, (human; Hemolink, Hemosol, Inc., Toronto, Ontario, Canada). METHODS: In the laboratory, 45 split canine plasma samples were mixed with hemoglobin glutamer-200 (8.13, 16.25, 32.5 g x L(-1) concentrations), 45 samples were mixed with hemoglobin glutamer-250 (8.13, 16.25, 32.5 g x L(-1) concentrations), 45 with hemoglobin-raffimer (12.5, 25.0, 50.0 g x L(-1) concentrations), and measured. Plasma samples without HBOC served as control. Hemoglobin concentration was determined by a laboratory analyzer (Coulter Corporation, Hiafeah, FL, USA) and B-hemoglobin photometer (HemoCue, Angelholm, Sweden). Two independent technicians performed blinded sample measurements and randomly tested each sample five times. Results were analyzed according to Bland and Altman analysis. RESULTS: B-hemoglobin photometer demonstrated high repeatability for all three HBOCs. Repeatability coefficients were 0.37 g x L(-1) and 0.48 g x L(-1) for hemoglobin glutamer-200, 0.39 g x L(-1) and 0.4 g x L(-1) for hemoglobin glutamer-250 and 1.07 g x L(-1) and 0.85 g x L(-1) for hemoglobin-raffimer. An acceptable agreement was found between the B-hemoglobin photometer and the laboratory analyzer for all three HBOCs tested. CONCLUSION: The B-hemoglobin photometer accurately determined the concentration of three HBOC solutions dissolved in canine plasma. 相似文献
97.
Analysis of lick rate measures the positive and negative feedback effects of carbohydrates on eating 总被引:1,自引:0,他引:1
Previous work has shown that measuring the rate of ingestion of liquid diets, rather than simply volume, reveals important features of ingestive behavior which can help to explain why a particular volume of a liquid is ingested. This study is an extension of that work to a variety of different test solutions. In this study the rate of ingestion of saccharin, two different concentrations of glucose and sucrose and their mixtures with saccharin and seven different concentrations of maltose were measured. The rate functions were fit by the least-squares method to a linear function to determine the intercepts and slope constants. Analysis of how these two parameters changed with the concentration and composition of the test solutions confirms, using different test solutions, a previously reported conclusion that the initial rate of ingestion (the intercept) measures palatability and that the slope constant is a measure of the rate of development of a negative feedback satiety signal. 相似文献
98.
Federico Licastro Richard Weindruch L. Jane Davis Roy L. Walford 《Age (Dordrecht, Netherlands)》1988,11(2):48-52
Effects of dietary restriction (DR) on DNA repair capacity of mouse splenocytes after ultraviolet (UV)-induced damage were
assessed. Two mouse cohorts received restricted amounts of purified hypocaloric diets; one was minimally restricted (∼75%
of the caloric intake of mice fed a commercial diet ad libitum), the other was severely restricted (∼50% caloric restriction). An inverse correlation between age and DNA repair was present
in the two cohorts; however, the regression lines of the two cohorts showed different slopes. DR appears to decelerate the
age-associated decline of DNA repair capacity, and this delay might account in part for the improved immune function shown
by old mice on DR. 相似文献
99.
100.
This article analyzes hidden status among crack, powder cocaine, and heroin users and setters, in contrast to more accessible users/sellers. Several sampling strategies acquired 657 users (N=559) and sellers (N=98). Indicators of hidden status were those who (1) paid rent in full in the last 30 days, (2) used nonstreet drug procurement. (3) had legal jobs, and (4) earned $1,000 or more in legal income in the last 30 days. Nearly half had at least one indicator: approximately 16% of users/sellers had two to four indicators. In logistic regression analyses, those who had not panhandled in the last 30 days, those who had used powder cocaine in the last 30 days, and those never arrested were the most likely to have hidden status, whether the analysis predicted those having any indicators or those having two to four indicators. The four indicators begin to operationally define hidden status among users of cocaine and heroin. 相似文献