Insulin-Like Growth Factor-I and Epidermal Growth Factor Regulate Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3) in the Human Keratinocyte Cell Line HaCaT

The human keratinocyte cell line HaCaT has a basal phenotype and secretes an insulin-like growth factor (IGF) binding protein, IGFBP-3, which modulates its IGF-I response. Keratinocytes are highly responsive to mitogenic stimulation by IGF-I and epidermal growth factor (EGF), but the effect of these growth factors on IGFBP secretion by keratinocytes is not known. We investigated the effects of IGF-I and EGF, as well as three other skin-growth regulators, retinoic acid, basic fibroblast growth factor, and dexamethasone, on mitogenic stimulation and IGFBP-3 production in HaCaT cells. IGF-I and EGF were strongly mitogenic, whereas retinoic acid, basic fibroblast growth factor, and dexamethasone were not significantly mitogenic. IGF-I increased the level of IGFBP-3 in cell-conditioned medium by up to two-fold, whereas EGF caused a twenty-fold reduction in IGFBP-3. Retinoic acid and basic fibroblast growth factor had only minor effects on IGFBP-3 and dexamethasone had no effect. IGF-I stimulation of IGFBP-3 did not involve increases in IGFBP-3 mRNA; however, EGF, consistent with its effect on IGFBP-3 protein, caused a fivefold reduction in IGFBP-3 mRNA. In summary, EGF profoundly inhibited IGFBP-3 synthesis in basal keratinocytes, whereas IGF-I increased IGFBP-3 levels by a post-transcriptional mechanism. We hypothesize that by inhibiting IGFBP-3 production in basal keratinocytes, epidermal mitogens such as EGF might stimulate epidermal growth indirectly by increasing local IGF-I availability

Comparison of large- and small-scale circulating fluidized bed combustors with respect to pollutant formation and reduction for different fuels

To investigate the scale-up problem of circulating fluidized bed combustors with particular respect to emissions, comparative combustion experiments have been performed in an industrial-size combustor (12 MWth, height 14 m, cross-sectional area 1.6 m X 1.6 m) and in a lab-scale facility (height 16 m, inner diameter 100 mm). A comparison of the axial concentration profiles of oxygen, carbon monoxide, nitric oxide, nitrous oxide and ammonia along the riser height, obtained during the combustion of wood, peat and coal under conditions of equal fuel bed material, solid holdup and gas residence time, shows a basic similarity. This indicates that suitably sized and operated lab-scale combustors may indeed be valuable tools for the investigation of combustion phenomena. However, some significant deviations of the profiles can be recognized, too. These deviations are caused by three-dimensional effects in the large-scale combustor and indicate the limitations of small-scale experiments

Looking back in time: conducting a cohort study of the long-term effects of treatment of adolescent tall girls with synthetic hormones

OBJECTIVE: Public health research is an endeavour that often involves multiple relationships, far-reaching collaborations, divergent expectations and various outcomes. Using the Tall Girls Study as a case study, this paper will present and discuss a number of methodological, ethical and legal challenges that have implications for other public health research. APPROACH: The Tall Girls Study was the first study to examine the long-term health and psychosocial effects of oestrogen treatment for tall stature. RESULTS: In undertaking this study the research team overcame many hurdles: in maintaining collaboration with treating clinicians and with the women they had treated as girls - groups with opposing points of view and different expectations; using private practice medical records to trace women who had been patients up to forty years earlier; and exploring potential legal issues arising from the collection of data related to treatment. CONCLUSION: While faced with complex challenges, the Tall Girls Study demonstrated that forward planning, ongoing dialogue between all stakeholders, transparency of processes, and the strict adherence to group-developed protocols were keys to maintaining rigour while undertaking pragmatic research. IMPLICATIONS: Public health research often occurs within political and social contexts that need to be considered in the planning and conduct of studies. The quality and acceptability of research findings is enhanced when stakeholders are engaged in all aspects of the research process

Prognostic impact of matched preoperative plasma and serum VEGF in patients with primary colorectal carcinoma

In serum, the major part of vascular endothelial growth factor derives from in vitro degranulation of granulocytes and platelets. Therefore, plasma may be preferred for vascular endothelial growth factor measurements. However, which specimen is the best predictor of survival is still debated. The present study analyzed the prognostic value of matched preoperative serum and plasma vascular endothelial growth factor concentrations in patients with colorectal cancer. To establish the reference range among healthy people, vascular endothelial growth factor was analyzed in 50 matched EDTA-plasma and serum samples from healthy blood donors. Preoperatively, in 524 patients with colorectal cancer, matched plasma and serum vascular endothelial growth factor concentrations were analyzed. In the colorectal cancer patients, the median plasma vascular endothelial growth factor concentration (44 pg ml−1) was significantly (P=0.01) higher than the median plasma vascular endothelial growth factor concentration (30 pg ml−1) in the healthy blood donors. In serum, no significant (P=0.30) difference in the median vascular endothelial growth factor concentration was found between colorectal cancer patients (268 pg ml−1) and healthy blood donors (220 pg ml−1). The preoperative vascular endothelial growth factor concentrations were dichotomized by the 95th percentile of the healthy blood donors (plasma=112 pg ml−1, serum=533 pg ml−1). In univariate survival analyses, both high plasma vascular endothelial growth factor (>112 pg ml−1) and high serum vascular endothelial growth factor (>533 pg ml−1) predicted a reduced survival. In multivariate survival analyses, high serum vascular endothelial growth factor (>533 pg ml−1) independently predicted a reduced survival (HR=1.65, P=0.015), while high plasma vascular endothelial growth factor (>112 pg ml−1) did not (HR=1.27, P=0.23). This study indicates that preoperative serum vascular endothelial growth factor apparently is a better predictor of overall survival than the preoperative plasma vascular endothelial growth factor

Co-combustion of sewage sludge with wood/coal in a circulating fluidised bed boiler - A study of NO and N2O emissions

Reduction of emissions of NO and N2O from co-combustion of wet or dried sewage sludge with coal or wood is investigated. This is motivated by the high nitrogen content in sewage sludge that may give rise to high emissions. An advanced air-staging method for combustion in circulating fluidised bed is applied. It is shown that with fluidised bed combustion the emissions are low as long as the sludge fraction is not too high (say, less than 25%), and the conversion of fuel nitrogen to NO or N2O is only a few percent. However, air staging as such is not efficient for high volatile fuels, and any air supply method can be applied in such a case, in contrast to combustion of coal, when the air supply arrangement has a decisive influence

Central Nervous System Function in Youth With Type 1 Diabetes 12 Years After Disease Onset

OBJECTIVE—In this study, we used neurocognitive assessment and neuroimaging to examine brain function in youth with type 1 diabetes studied prospectively from diagnosis

IgG light chain-independent secretion of heavy chain dimers: consequence for therapeutic antibody production and design

Rodent monoclonal antibodies with specificity towards important biological targets are developed for therapeutic use by a process of humanisation. This process involves the creation of molecules, which retain the specificity of the rodent antibody but contain predominantly human coding sequence. Here we show that some humanised heavy chains can fold, form dimers and be secreted even in the absence of light chain. Quality control of recombinant antibody assembly in vivo is thought to rely upon folding of the heavy chain CH1 domain. This domain acts as a switch for secretion, only folding upon interaction with the light chain CL domain. We show that the secreted heavy-chain dimers contain folded CH1 domains and contribute to the heterogeneity of antibody species secreted during the expression of therapeutic antibodies. This subversion of the normal quality control process is dependent upon the heavy chain variable domain, is prevalent with engineered antibodies and can occur when only the Fab fragments are expressed. This discovery will impact on the efficient production of both humanised antibodies as well as the design of novel antibody formats

Co-firing of biomass and other wastes in fluidised bed systems

A project on co-firing in large-scale power plants burning coal is currently funded by the European Commission. It is called COPOWER. The project involves 10 organisations from 6 countries. The project involves combustion studies over the full spectrum of equipment size, ranging from small laboratory-scale reactors and pilot plants, to investigate fundamentals and operating parameters, to proving trials on a commercial power plant in Duisburg. The power plant uses a circulating fluidized bed boiler. The results to be obtained are to be compared as function of scale-up. There are two different coals, 3 types of biomass and 2 kinds of waste materials are to be used for blending with coal for co-firing tests. The baseline values are obtained during a campaign of one month at the power station and the results are used for comparison with those to be obtained in other units of various sizes. Future tests will be implemented with the objective to achieve improvement on baseline values. The fuels to be used are already characterized. There are ongoing studies to determine reactivities of fuels and chars produced from the fuels. Reactivities are determined not only for individual fuels but also for blends to be used. Presently pilot-scale combustion tests are also undertaken to study the effect of blending coal with different types of biomass and waste materials. The potential for synergy to improve combustion is investigated. Early results will be reported in the Conference. Simultaneously, studies to verify the availability of biomass and waste materials in Portugal, Turkey and Italy have been undertaken. Techno-economic barriers for the future use of biomass and other waste materials are identified. The potential of using these materials in coal fired power stations has been assessed. The conclusions will also be reported