Regulation of ZAP-70 Intracellular Localization: Visualization with the Green Fluorescent Protein

To investigate the cellular dynamics of ZAP-70, we have studied the distribution and regulation of its intracellular location using a ZAP-70 green fluorescent protein chimera. Initial experiments in epithelial cells indicated that ZAP-70 is diffusely located throughout the quiescent cell, and accumulates at the plasma membrane upon cellular activation, a phenotype enhanced by the coexpression of Lck and the initiation of ZAP-70 kinase activity. Subsequent studies in T cells confirmed this phenotype. Intriguingly, a large amount of ZAP-70, both chimeric and endogenous, resides in the nucleus of quiescent and activated cells. Nuclear ZAP-70 becomes tyrosine phosphorylated upon stimulation via the T cell receptor, indicating that it may have an important biologic function.     

疼痛对乳腺癌患者生活质量影响调查

目的了解乳腺癌患者的疼痛感受和生活质量状况，评估疼痛对生活质量的影响程度。方法采用中国人癌症疼痛评估工具（Chinese Cancer Pain Assessment Tool，CCPAT）和生活质量调查问卷（第3版）[EORTIC QLQ—C30（Version 3）]对200例乳腺癌患者进行横断面设计的面对面问卷调查。结果200例乳腺癌患者中有疼痛者84例（42％），无疼痛者116例（58％）.疼痛组患者疼痛评分高于非疼痛组患者评分（P〈0．001）.疼痛组患者在生活质量的躯体功能领域、角色功能领域和社会功能领域的评分低于无疼痛组患者，其差异有统计学意义（P〈0．05）；两组患者在生活质量的情绪功能领域、认知功能领域和整体生活质量的评分差异无统计学意义（P〉0．05）；疼痛组患者的疼痛评分与整体生活质量评分呈显著负相关（r=-0．731，P〈0．001）.结论疼痛对乳腺癌患者的躯体功能、角色功能和社会功能有一定的负面影响；患者受疼痛的冲击加重时，其整体生活质量降低。     

Mortality and the nature of metabolic acidosis in children with shock

HYPOTHESIS: Mortality in children with shock is more closely related to the nature, rather than the magnitude (base deficit/excess), of a metabolic acidosis. OBJECTIVE: To examine the relationship between base excess (BE), hyperlactataemia, hyperchloraemia, 'unmeasured' strong anions, and mortality. DESIGN: Prospective observational study set in a multi-disciplinary Paediatric Intensive Care Unit (PICU). PATIENTS: Forty-six children, median age 6 months (1.5-14.4), median weight 5 kg (3.2-8.8), admitted to PICU with shock. INTERVENTIONS: Predicted mortality was calculated from the paediatric index of mortality (PIM) score. The pH, base excess, serum lactate, corrected chloride, and 'unmeasured' strong anions (Strong Ion Gap) were measured or calculated at admission and 24 h. MEASUREMENTS AND RESULTS: Observed mortality ( n=16) was 35%, with a standardised mortality ratio (SMR) of 1.03 (95% CI 0.71-1.35). There was no significant difference in admission pH or BE between survivors and nonsurvivors. There was no association between elevation of 'unmeasured' anions and mortality, although there was a trend towards hyperchloraemia in survivors ( P=0.08). Admission lactate was higher in nonsurvivors (median 11.6 vs 3.3 mmol/l; P=0.0003). Area under the mortality receiver operating characteristic curve for lactate was 0.83 (955 CI 0.70-0.95), compared to 0.71 (95% CI 0.53-0.88) for the PIM score. Admission lactate level >5 mmol/l had maximum diagnostic efficiency for mortality, with a likelihood ratio of 2.0. CONCLUSION: There is no association between the magnitude of metabolic acidosis, quantified by the base excess, and mortality in children with shock. Hyperlactataemia, but not elevation of 'unmeasured' anions, is predictive of a poor outcome.     

Neonatal procedural pain exposure predicts lower cortisol and behavioral reactivity in preterm infants in the NICU

Data from animal models indicate that neonatal stress or pain can permanently alter subsequent behavioral and/or physiological reactivity to stressors. However, cumulative effects of pain related to acute procedures in the neonatal intensive care unit (NICU) on later stress and/or pain reactivity has received limited attention. The objective of this study is to examine relationships between prior neonatal pain exposure (number of skin breaking procedures), and subsequent stress and pain reactivity in preterm infants in the NICU. Eighty-seven preterm infants were studied at 32 (+/-1 week) postconceptional age (PCA). Infants who received analgesia or sedation in the 72 h prior to each study, or any postnatal dexamethasone, were excluded. Outcomes were infant responses to two different stressors studied on separate days in a repeated measures randomized crossover design: (1) plasma cortisol to stress of a fixed series of nursing procedures; (2) behavioral (Neonatal Facial Coding System; NFCS) and cardiac reactivity to pain of blood collection. Among infants born 相似文献   

Clients Served and Services Provided by Academic Nurse-Managed Centers

Currently, no national database for academic nurse-managed centers (ANMCs) exists. These primary care services remain somewhat invisible in the policy and reimbursement areas of the American primary care system and, consequently, are undersupported. The purpose of this article is to describe client and service data from a national study of ANMCs. A cross-sectional survey design was used to collect data from ANMC directors. Usable data were received from 64 centers. ANMCs in the sample were relatively small in terms of patients and volume. Client and service profiles demonstrated variation, which seemed to be reflective of needs relative to populations and communities served. Nearly half of the ANMCs responding served clients of all ages, with services representing the breadth of primary care (i.e., health maintenance and management of minor acute and common chronic illnesses). Evidence of community-focused care was also noted. The reported use of standardized nursing language was low. Standardized medical taxonomies were more commonly used, with International Classification of Diseases, Ninth Revision being the most common. ANMCs provide a small but substantial amount of primary care services in communities served. Findings indicated a need for ANMCs to improve the documentation of their contributions through the use of standardized taxonomies to provide aggregated reporting for policy and research purposes.     

A 7-deaza-adenosine analog is a potent and selective inhibitor of hepatitis C virus replication with excellent pharmacokinetic properties

Improved treatments for chronic hepatitis C virus (HCV) infection are needed due to the suboptimal response rates and deleterious side effects associated with current treatment options. The triphosphates of 2'-C-methyl-adenosine and 2'-C-methyl-guanosine were previously shown to be potent inhibitors of the HCV RNA-dependent RNA polymerase (RdRp) that is responsible for the replication of viral RNA in cells. Here we demonstrate that the inclusion of a 7-deaza modification in a series of purine nucleoside triphosphates results in an increase in inhibitory potency against the HCV RdRp and improved pharmacokinetic properties. Notably, incorporation of the 7-deaza modification into 2'-C-methyl-adenosine results in an inhibitor with a 20-fold-increased potency as the 5'-triphosphate in HCV RdRp assays while maintaining the inhibitory potency of the nucleoside in the bicistronic HCV replicon and with reduced cellular toxicity. In contrast, while 7-deaza-2'-C-methyl-GTP also displays enhanced inhibitory potency in enzyme assays, due to poor cellular penetration and/or metabolism, the nucleoside does not inhibit replication of a bicistronic HCV replicon in cell culture. 7-Deaza-2'-C-methyl-adenosine displays promising in vivo pharmacokinetics in three animal species, as well as an acute oral lethal dose in excess of 2,000 mg/kg of body weight in mice. Taken together, these data demonstrate that 7-deaza-2'-C-methyl-adenosine is an attractive candidate for further investigation as a potential treatment for HCV infection.