Sequential cytogenetic and molecular cytogenetic characterization of an SV40T-immortalized nasopharyngeal cell line transformed by Epstein-Barr virus latent membrane protein-1 gene

Cytogenetic and molecular cytogenetic analyses were performed on four sublines derived from a newly established, SV40T-immortalized nasopharyngeal (NP) cell line, NP69, with two of the sublines expressing LMP1, an Epstein-Barr virus–encoded gene. A total of seven cytogenetically related subclones were identified, all having highly complex karyotypes with massive numerical and structural rearrangements. Centromeric rearrangements in the form of isochromosomes and whole-arm translocations were prevalent. A cytogenetic sign of gene amplification [i.e., homogeneously staining region (HSR)] was detected at 1q25 in all metaphase cells analyzed. Multicolor combined binary ratio labeling fluorescence in situ hybridization (COBRA-FISH) was used to confirm the karyotypic interpretations. Furthermore, multicolor COBRA-FISH also showed that part of the HSR contained chromosome 20 material. Extensive clonal evolution could be observed by the assessment of karyotypic variation among different subclones and individual metaphase cells. The evaluation of clonal evolution enabled the identification of the temporal order of chromosome aberrations during cell immortalization and malignant transformation. A striking karyotypic similarity was found between sublines expressing LMP1 and an NP carcinoma cell line, with loss of genetic material from chromosome arm 3p being an important recurrent observation. More interestingly, the karyotypic features of NP69 were also similar to those of many epithelial malignancies. Our observations suggest that serial transformation of NP cell lines might provide a useful in vitro model for the study of the multistep neoplastic transformation of NP cells.     

The coordination of signaling during Fc receptor-mediated phagocytosis

Phagocytosis by macrophages can be initiated by Fcgamma receptors (FcR) in membranes that bind to Fc regions of immunoglobulin G (IgG). Activated FcR transduce signals to cytoplasm, which regulate the internalization of IgG-coated particles into plasma membrane-derived vacuoles, phagosomes. Particles internalized by phagocytosis are much larger than FcR, which prompts questions of if and how the receptors are coordinated with each other. FcR-mediated signal transduction entails recruitment of proteins from cytoplasm to the receptor, largely via protein phosphorylation. These FcR signaling complexes then activate proteins that regulate actin, myosin, membrane fusion, and the production of reactive oxygen intermediates. Recent fluorescence microscopic studies of phagocytosis in macrophages indicate that signaling by FcR occurs as a sequence of distinct stages, evident in the spatial and temporal patterns of phosphoinositides, protein kinase C, and Rho-family GTPase activation on forming phagosomes. The coordination of these stages may be regulated by lipids or lipid-anchored proteins, which diffuse away from FcR complexes. Lateral diffusion of FcR-derived signals could integrate FcR-dependent responses over large areas of membrane in the forming phagosome.     

A Danish diabetes risk score for targeted screening: the Inter99 study

OBJECTIVE: To develop a simple self-administered questionnaire identifying individuals with undiagnosed diabetes with a sensitivity of 75% and minimizing the high-risk group needing subsequent testing. RESEARCH DESIGN AND METHODS: A population-based sample (Inter99 study) of 6,784 individuals aged 30-60 years completed a questionnaire on diabetes-related symptoms and risk factors. The participants underwent an oral glucose tolerance test. The risk score was derived from the first half and validated on the second half of the study population. External validation was performed based on the Danish Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care (ADDITION) pilot study. The risk score was developed by stepwise backward multiple logistic regression. RESULTS: The final risk score included age, sex, BMI, known hypertension, physical activity at leisure time, and family history of diabetes, items independently and significantly (P<0.05) associated with the presence of previously undiagnosed diabetes. The area under the receiver operating curve was 0.804 (95% CI 0.765-0.838) for the first half of the Inter99 population, 0.761 (0.720-0.803) for the second half of the Inter99 population, and 0.803 (0.721-0.876) for the ADDITION pilot study. The sensitivity, specificity, and percentage that needed subsequent testing were 76, 72, and 29%, respectively. The false-negative individuals in the risk score had a lower absolute risk of ischemic heart disease compared with the true-positive individuals (11.3 vs. 20.4%; P<0.0001). CONCLUSIONS: We developed a questionnaire to be used in a stepwise screening strategy for type 2 diabetes, decreasing the numbers of subsequent tests and thereby possibly minimizing the economical and personal costs of the screening strategy.     

Psychiatric nursing case management: past, present, and future

This literature review examines the evolution of psychiatric nursing case management in the United States. Various models, both inpatient and outpatient, are described, along with the roles of the case manager in each setting. The development of clinical pathways to monitor and document outcomes in acute settings is examined, along with the difficulties in adapting them specifically to psychiatric nursing case management. The types of data collected and the use of outcomes to support programs for the mentally ill are reviewed. Finally, recommendations for psychiatric nursing case management are made to provide guidelines for the future.     

Decreased UCP2 mRNA expression in rat stomach following vagotomy: novel role for UCP2 as free radical scavenger in the stomach?

Uncoupling protein 2 (UCP2) is a protein, located in the inner mitochondrial membrane, which dissipates the proton gradient of this membrane and uncouples respiration from oxidative phosphorylation. We found, by in situ hybridisation, UCP2 mRNA to be located in the proliferating zone of the mucous neck cells in the fundus part of the rat stomach. We also found that UCP2 expression in fundus was significantly decreased after seven days of vagotomy. Furthermore, we found manganese-containing superoxide dismutase (SOD2), in fundus, to be down-regulated in a way similar to UCP2. The amount of ATP was significantly decreased following vagotomy. It is concluded that UCP2 in the gastro-intestinal tract is regulated through vagal innervation and suggested to act as a free radical scavenger.