The tumor-specific de2-7 epidermal growth factor receptor (EGFR) promotes cells survival and heterodimerizes with the wild-type EGFR

Mutations of the epidermal growth factor receptor (EGFR) gene are found at a relatively high frequency in glioma, with the most common being the de2-7 EGFR (or EGFRvIII). This mutation arises from an in-frame deletion of exons 2-7, which removes 267 amino acids from the extracellular domain of the receptor. Despite being unable to bind ligand, the de2-7 EGFR is constitutively active and imparts a significant in vivo growth advantage to glioma cells. In order to examine the signalling pathways activated by the de2-7 EGFR and its biological effects in an in vitro system, the de2-7 EGFR gene was transfected into the murine IL-3-dependent pro-B-cell line BaF/3. Expression of the de2-7 EGFR enhanced the survival of BaF/3 cells in the absence of IL-3 by reducing apoptosis in a phosphatidylinositol 3-kinase (PI3-K)-dependent manner. Interestingly, while de2-7 EGFR also enhanced proliferation of BaF/3 cells in low levels of IL-3, this effect was independent of PI3-K. Survival and proliferation were further enhanced when BaF/3 cells were cotransfected with the de2-7 and wt EGFR. This was due to heterodimerization between the de2-7 and wt EGFR leading to trans-phosphorylation of the wt EGFR. This observation is directly relevant to glioma where de2-7 and wt EGFR appear to be coexpressed. Thus, expression of de2-7 EGFR in BaF/3 cells provides an in vitro model for evaluating the signalling pathways activated by this receptor.     

Low-intensity laser therapy/combined phototherapy in the management of chronic venous ulceration: a placebo-controlled study

OBJECTIVE: The current placebo-controlled study was undertaken to investigate the efficacy of combined phototherapy and low-intensity laser therapy (LILT) in the management of chronic venous ulceration when used in conjunction with standardized nursing intervention. MATERIALS AND METHODS: Approval was granted by Research Ethical Committees at the University of Ulster and Altnagelvin Hospitals Health and Social Services Trust. Patients (n = 15; 10 female/5 male; age +/- SD = 69.9 +/- 13.8 years) were recruited from an outpatient "leg ulcer clinic," where they attended once per week for irradiation/sham treatments for 4 weeks. Treatment was withheld for a total of 8 weeks, and patients were reviewed during this time (weeks 8 and 12) for ulcer and pain assessment only. A multisource diode array (660-950 nm) was used for irradiation; parameters were kept constant for the duration of the study (532 mW; 5 kHz; 12 J/cm(2)). Wound and pain assessment were carried out by an independent investigator. Digitizing was used to quantify surface areas from wound tracings. RESULTS: Although there was no statistically significant difference between Treatment and Placebo groups, an apparent clinical difference in wound healing rate was noted; at postirradiation, a continued reduction in wound size was evident for the treatment group. These effects were believed to be due to an apparent delayed effect. There was no statistically significant difference between groups for pain. CONCLUSION: These findings provide only limited evidence for the use of this modality as an adjunctive therapy with current nursing intervention. Further group studies are indicated to investigate the apparent delayed effect reported here for various etiologies of ulceration.     

Application of a hybrid analysis method for a Web-enabled information system: a case study

A successful developmental effort frequently is defined as one that produces a deliverable that is satisfactory to the client, on time, within budget, and has had no adverse impact on ongoing business operations. This article describes through a case study approach the activities that one project used to ensure a successful development effort. The author advocates a hybrid methodological approach to systems analysis and design that is tailored for the specific project. The article also describes the project and people management practices used to support the developmental effort.     

Relation of electromyography-induced pain to type of recording electrodes

Pain is an important consideration in the performance of needle electromyography (EMG). Prior investigations have suggested that pain is greater with a concentric needle electrode (CNE) than monopolar needle electrode (MNE). This prospective randomized study tested this hypothesis using improved methodology and disposable rather than reusable needle electrodes. Ninety consecutive outpatients were enrolled and randomized to CNE (diameter = 0.46 mm) or MNE (diameter = 0.41 mm) arms. Subjects underwent a standardized 4 limb-muscle needle EMG protocol during which pretest and posttest verbal analog pain scale (0-10) measures were obtained. As anticipated, EMG-induced pain was significantly higher (P < 0.001) than pre-EMG baseline pain. However, analysis of variance (ANOVA) revealed no significant differences in pain ratings between the CNE and MNE arms. Among other factors analyzed, only gender significantly influenced EMG-induced pain, with females reporting higher levels than males. Thus, pain is not an important selection criterion for type of disposable needle electrode.