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31.
To evaluate the utility of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a cancer therapeutic, we created leucine zipper (LZ) forms of human (hu) and murine (mu) TRAIL to promote and stabilize the formation of trimers. Both were biologically active, inducing apoptosis of both human and murine target cells in vitro with similar specific activities. In contrast to the fulminant hepatotoxicity of LZ-huCD95L in vivo, administration of either LZ-huTRAIL or LZ-muTRAIL did not seem toxic to normal tissues of mice. Finally, repeated treatments with LZ-huTRAIL actively suppressed growth of the TRAIL-sensitive human mammary adenocarcinoma cell line MDA-231 in CB.17 (SCID) mice, and histologic examination of tumors from SCID mice treated with LZ-huTRAIL demonstrated clear areas of apoptotic necrosis within 9-12 hours of injection.  相似文献   
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This research derives and tests hypotheses from two alternative conceptual models: the modified extended family model, and the changing family constraints model, which takes into account recent changes in work and family life. The hypotheses address social class differences in geographic distance and contact frequency between middle-aged children and their parents over time. Simultaneous probit models are used to analyze distance and contact as jointly determined outcomes with data from the USC Longitudinal Study of Generations and Mental Health. Results from these analyses indicate that children's 1971 educational aspirations and social class positions predict 1991 distance and contact between generations. Parents who have lower 1991 incomes, however, live farther from children and talk with them on the telephone less frequently than higher-income parents. Thus, the effects of early social class position support the modified extended family model, whereas the effects of current social class position support the changing family constraints model.  相似文献   
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The spatial and temporal pattern of expression of enhancer trap lines reporting on the wingless (wg) and engrailed (en) genes was characterized in the adult antenna of Drosophila melanogaster. The time courses of expression seen for wg and en, although different from each other, reveal a complex well-controlled pattern of temporal expression, providing evidence that regulatory mechanisms are preserved throughout the life span of the adult fly. Altering the life span demonstrates that the temporal patterns of expression of both wg and en are linked to life span. These studies suggest that the expression of wg and en in the adult antenna is controlled by age-dependent mechanisms.  相似文献   
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Gag rules-clauses in managed care contracts that prevent physicians from disclosing information that the plan may find disparaging, but that could relate directly to the patient's health-have recently been the subject of ethical condemnation and legislative prohibition. Another serious problem in managed care contracts, trade secrets, or guidelines and quality assurance mechanisms that are imposed on physicians while their origins are shrouded in proprietary secrecy, have by contrast received little attention. Responses to these ethical challenges to the physician's integrity must involve individual physicians, managed care organizations, professional organizations, and public policymakers.  相似文献   
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The objective of our study was to assess the long-term outcome of patients with prosthetic valve endocarditis. We used a multicenter, prospective, observational study design. Six university teaching hospitals with high volume cardiothoracic surgery participated. Seventy-four patients with prosthetic valve endocarditis as defined by explicit, objective criteria were selected for participation. All patients were followed up prospectively for 1 year. Thirty-one percent and 69% had development of endocarditis within 60 days of valve insertion ("early") and after 60 days ("late"), respectively. The most common causes were Staphylococcus epidermidis (40%), Staphylococcus aureus (20%), streptococcal species (18%), and aerobic gram-negative bacilli (11%). Physical signs of endocarditis (new or changing murmur, stigmata, emboli) were seen in 58%. At 6 months and 12 months, mortality was 46% and 47%, respectively. Surgical replacement of the infected valve led to significantly lower mortality (23%) as compared with medical therapy alone (56%), as assessed by both univariate and multivariate analyses (p < 0.05). Improved outcome was seen for the surgical group even when controlling for severity of illness at time of diagnosis. From these findings we conclude that accurate assessment of outcome in prosthetic valve endocarditis requires long-term follow-up of at least 6 months following diagnosis. Surgical therapy warrants greater scrutiny; evaluation in controlled clinical trials is appropriate.  相似文献   
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We suggest that toroidal structures in the state of psi-condensation of DNA may be caused by anisotropy on a meso-scale of several thousand A, the conformation of a DNA-molecule being determined by its elasticity and neutralization of phosphate charge. We model a molecule of B-DNA on an anisotropic elastic rod subject to a torque, and make the numerical simulation of the model that reveals that under appropriate conditions, which may be effected in experimental setting by changing the concentration of polymeric solutions, there are toroidal structures having the size of a few persistence lengths, in agreement with the experimental data. On changing the elastic modulii or characteristics of the counterion layer, we see the toroidal structures turn into the spherical ones. To understand the function of anisotropy it would be interesting to investigate the Z-DNA as regards psi-condensation.  相似文献   
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OBJECTIVE: Cholelithiasis is a common problem in hospitals of the Peruvian Andes; however, its prevalence in Andean communities is unknown. To estimate the prevalence of gallstone disease in this locale, we conducted a cross-sectional community study in three high-altitude Peruvian rural villages (i.e., > 3000 m above sea level). METHODS: We examined 911 volunteers > 15 yr of age from three villages for gallstone disease by history and ultrasonography. Risk factors for gallstone disease were examined in 382 volunteers from one village. RESULTS: The age-adjusted prevalence of gallstone disease ranged from 4-10% in men and from 18-20% in women. Women had significantly higher age-adjusted prevalence rates than did men. The prevalence of gallstone disease increased significantly with age and decreased significantly with alcohol consumption. Although not statistically significant, we found a positive association between gallstone disease and body mass index. CONCLUSION: The results of this study indicate that gallstone disease, commonly perceived as a disease of the developed world, is also a common problem in high-altitude Peruvian communities.  相似文献   
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