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91.
Greenberg MH Levin-Epstein J Hutson RQ Ooms TJ Schumacher R Turetsky V Engstrom DM 《The Future of children / Center for the Future of Children, the David and Lucile Packard Foundation》2002,12(1):26-57
The Personal Responsibility and Work Opportunity Reconciliation Act of 1996 changed the social policy landscape for children in many ways. It replaced the prior welfare program with block grants to the states entitled Temporary Assistance for Needy Families, and modified a broad array of other programs and initiatives affecting low-income children. This article describes the key themes dominating the debate over welfare reform in 1996, specifically: Increased state discretion in program design, leading to more variability in states' eligibility requirements and services provided to low-income families; More stringent work requirements even for parents of very young children; Time limits on the use of federal funds for cash assistance, and a strong focus on caseload reduction; Increased emphasis on parental responsibility, with stronger child support requirements; and Increased emphasis on reducing out-of-wedlock births, including bonuses to states with the largest reductions, and special requirements for unmarried teen parents who seek welfare. Although child well-being received little attention during the congressional debates in 1996, the authors conclude with the hope that improving child outcomes and child well-being will emerge as a key theme when the law is reauthorized in 2002. 相似文献
92.
Attentional orienting towards smoking-related stimuli 总被引:1,自引:0,他引:1
According to incentive salience theory, conditioned stimuli (CS+) associated with drug reinforcement acquire the capacity to elicit a conditioned attentional orienting response, which controls drug-seeking and drug-taking behaviour. We sought evidence for this proposal by measuring visual attentional orienting towards smoking pictures presented briefly in the periphery of the visual field, versus control pictures likewise presented, in smokers versus non-smokers. In each trial, smokers and non-smokers responded manually to a dot probe stimulus that appeared in a location previously occupied by either a smoking picture or a control picture. Attentional bias scores were calculated by subtracting the median reaction time (RT) in the former condition from the median RT in the latter condition. In two experiments, light-smokers (smokers of fewer than 20 cigarettes/day) produced a mean bias score that was significantly greater than that of heavy-smokers (smokers of 20 or more cigarettes/day) and non-smokers. In addition, when smokers from the two experiments were pooled, a significant quadratic relationship was found between cigarettes/day and the attentional bias for the smoking stimuli. These findings are consistent with incentive salience theories and dual-process theories of addiction. 相似文献
93.
Expression of the lipogenic enzyme fatty acid synthase (FAS) in retinoblastoma and its correlation with tumor aggressiveness 总被引:4,自引:0,他引:4
Camassei FD Cozza R Acquaviva A Jenkner A Ravà L Gareri R Donfrancesco A Bosman C Vadalà P Hadjistilianou T Boldrini R 《Investigative ophthalmology & visual science》2003,44(6):2399-2403
PURPOSE: Fatty acid synthase (FAS) performs the anabolic conversion of dietary carbohydrate or protein to fatty acids. Many common human cancers express high levels of FAS, and its differential expression between normal and neoplastic tissues has led to the consideration of FAS as a target for anticancer therapy. To investigate the potential of targeting FAS in the treatment of retinoblastoma, we first determined whether FAS was activated in this human tumor. Moreover, correlation of FAS expression with tumor aggressiveness was determined. METHODS: FAS reactivity was evaluated by immunohistochemistry in 66 retinoblastoma specimens from 65 patients. Degree of tumor differentiation, choroid invasion, optic nerve infiltration, mitotic rate, and necrosis extension were estimated. FAS expression was correlated with all these tumor characteristics by means of parametric and nonparametric statistical analyses. RESULTS: Eighty-two percent of tumors were FAS positive. Stronger FAS expression correlated with more advanced choroid (P < 0.001) and optic nerve (P = 0.016) invasion, high mitotic index (P < 0.001), and less differentiated histology (P = 0.047). Correlation with extension of necrosis was not statistically significant. Unaffected retina was negative. CONCLUSIONS: The data suggest that expression of FAS and fatty acid synthesis support an essential functional aspect of retinoblastoma cells, perhaps cell growth or survival. FAS activation may serve as a novel target for systemic and local antineoplastic therapy and, because it increases with tumor aggressiveness, its inhibition could represent an alternative treatment strategy in advanced and resistant retinoblastomas. 相似文献
94.
95.
Systemic injections of alcohol have previously been reported to 'prime' or to reinstate self-administration of alcohol in rats, and it has been suggested that the priming effects of drugs are related to their stimulus properties. We tested this hypothesis by investigating the effects of lorazepam, which cross-generalizes with alcohol in animal drug-discrimination studies, in rats trained to self-administer 7% alcohol in an operant paradigm. Once animals were trained, extinction tests were carried out twice weekly, before which rats were injected with either vehicle, alcohol (0.063-0.5 g/kg, i.p.) or lorazepam (0.03-0.25 mg/kg, i.p.). Alcohol did not increase responding for alcohol during extinction. Doses of 0.25 and 0.5 g/kg reduced alcohol-appropriate lever pressing (p < 0.05 versus 0 g/kg), with the largest dose also suppressing general activity (p < 0.02 versus 0 g/kg). Lorazepam also reduced alcohol-appropriate responding, in a behaviourally specific manner; doses of 0.03 mg/kg and above decreased lever pressing (p < 0.05 versus 0 mg/kg), whereas general activity was depressed at 0.06 mg/kg and larger doses (p < 0.05 versus 0 mg/kg). Although lorazepam mimicked the effect of alcohol at doses predicted to do so on the basis of their relative potency in drug discrimination studies, neither alcohol nor lorazepam primed rats to respond for alcohol. By contrast, the pattern of results suggested that, in this model, they 'satiated' or substituted for alcohol, resulting in a reduced motivation to respond. 相似文献
96.
97.
Rao DS Bradley SV Kumar PD Hyun TS Saint-Dic D Oravecz-Wilson K Kleer CG Ross TS 《Cancer cell》2003,3(5):471-482
The clathrin-associated protein, Huntingtin Interacting Protein 1 (HIP1), is overexpressed in multiple human epithelial tumors. Here, we report that HIP1 is a novel oncoprotein that transforms cells. HIP1-transformed cells, in contrast to RasV12-transformed cells, have dysregulation of multiple receptors involved in clathrin trafficking. Examples include upregulation of the epidermal growth factor receptor (EGFR) and the transferrin receptor. Furthermore, accumulation of transferrin and EGF in the HIP1-transformed cells was increased, and breast tumors that had EGFR expressed also had HIP1 upregulated. Thus, HIP1 overexpression promotes tumor formation and is associated with a general alteration in receptor trafficking. HIP1 is the first endocytic protein to be directly implicated in tumor formation. 相似文献
98.
A whole genome association study in Icelandic multiple sclerosis patients with 4804 markers 总被引:8,自引:0,他引:8
Jonasdottir A Thorlacius T Fossdal R Jonasdottir A Benediktsson K Benedikz J Jonsson HH Sainz J Einarsdottir H Sigurdardottir S Kristjansdottir G Sawcer S Compston A Stefansson K Gulcher J 《Journal of neuroimmunology》2003,143(1-2):88-92
Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system (CNS) with a complex genetic background. Here we use a genome-wide association strategy with 4804 microsatellite markers successfully typed in separately pooled DNA from 200 patients and 200 controls. A total of 91 markers showed evidence of association. When compared to our in-house physical map of the genome, six 2-Mb regions containing at least two of these markers were detected. Of those, three regions have one or more markers among the 20 most strongly associated: chromosomes 3q25, 6p21.3 (the MHC region) and 19q13. 相似文献
99.
Martins Silva B Thorlacius T Benediktsson K Pereira C Fossdal R Jonsson HH Silva A Leite I Cerqueira J Costa PP Marta M Foltynie T Sawcer S Compston A Jonasdottir A 《Journal of neuroimmunology》2003,143(1-2):116-119
Genetic factors are known to influence susceptibility to multiple sclerosis (MS) but the genes involved are largely undefined. Here, we report an association study based on 200 patients and 200 controls from the Porto region in Portugal. A total of 3974 markers were successfully typed from which we have identified 46 markers showing evidence of association. When compared to a physical map three regions were found with two of these markers less than 1.5 Mb apart: chromosomes 6p21.3 (the MHC region), 6q14.1 and 7q34. 相似文献
100.
Salzberg-Brenhouse HC Chen EY Emerich DF Baldwin S Hogeland K Ranelli S Lafreniere D Perdomo B Novak L Kladis T Fu K Basile AS Kordower JH Bartus RT 《The Journal of pharmacology and experimental therapeutics》2003,306(1):218-228
Cyclooxygenases (COXs) are implicated in neurodegenerative processes associated with acute and chronic neurological diseases. Given the potential utility of COX inhibitors in treating these disorders, we examined the nonselective COX inhibitor flurbiprofen, the specific COX-1 inhibitor valeryl salicylate (VS), and the COX-2 inhibitor N-[2-(cyclohexyloxy)-4-nitrophenyl]methanesulfonamide (NS-398) for their abilities to protect striatal neurons against a quinolinic acid (QA)-induced excitotoxic lesion. Rats were administered COX inhibitors 10 min before a unilateral QA lesion of the striatum, and then tested 2 to 3 weeks later in a battery of motor tasks (bracing, placing, akinesia, and apomorphine-induced rotations). Lesion volume was assessed using immunohistochemical methods 1 month after lesioning. Orally administered flurbiprofen (50 mg) was highly neuroprotective, preserving 84 to 99% of motor performance (ED50 = 8.6-9.7 mg) while reducing lesion volume 75% (ED50 = 3.2 mg). The identities of the COX isoforms associated with QA-induced neurodegeneration were determined using VS and NS-398. Oral VS was ineffective in virtually all indices of functional neuroprotection. In contrast, oral NS-398 was highly effective, preserving approximately 83% of motor performance at2mg(ED50 = 0.1-0.4 mg), and reducing lesion volume 100% (ED50 = 0.4 mg). Similar results were obtained using inhaled flurbiprofen (2 mg), which preserved 88 to 100% of motor performance while reducing striatal lesion size 92%. These results demonstrate that COX-2 inhibition protects neurons from acute, excitotoxic neurodegeneration. Moreover, formulating a nonselective COX inhibitor into an inhalable preparation dramatically improves its potency in treating acute neuronal damage, a situation where the rapidity of drug delivery and onset of action is critical to clinical efficacy. 相似文献