The use of natural interferon alpha conjugated to a monoclonal antibody anti mammary epithelial mucin (Mc5) for the treatment of human breast cancer xenografts

An immunoconjugate composed of natural interferon alpha (nIFN alpha) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN alpha/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN alpha/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN alpha on the injected tumors. Further enhancement was obtained when nIFN gamma or nIFN gamma together with Mc5 (at a dose 10 times larger than that present in nIFN alpha/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of 125I-nIFN alpha/Mc5 by the tumors was greater and its elimination slower than for 125I-nIFN alpha alone or conjugated to irrelevant mouse IgG1. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alpha alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy.     

Central poststroke pain and Wallenberg''s lateral medullary infarction: frequency, character, and determinants in 63 patients

BACKGROUND: Questionnaire-based surveys from several countries have consistently detected adverse health associated with home dampness and mould growth. METHODS: To test the validity of questions commonly used to indicate the presence of indoor mould, questionnaires were administered in 403 homes where dust samples were taken for viable fungi and air samples for ergosterol. RESULTS: Geometric mean concentrations of the total viable fungi were 255 (SE 116) x 10(3) CFU/g when mouldy odours were reported and 155 (SE 55) when odours were not reported (P = 0.01). Similarly, reported water damage was associated with a 50% increase (P = 0.06). Geometric mean concentrations of the predominantly indoor-source fungi, Aspergillus plus Penicillium, were twice as high when mould or mildew was reported than when not mentioned (P = 0.01). The presence of reported mould or water damage was unrelated to the presence of detectable levels of ergosterol. There was evidence for reporting bias: in the presence of low concentrations of viable fungi in dust, respondents reporting allergies were more likely to report visible mould growth (odds ratio [OR] = 1.8, 95% confidence interval [CI]: 0.9-3.5, P = 0.10. In the presence of elevated concentrations of dust fungi, respondents who smoked were less likely to report visible mould growth, (OR = 0.4, 95% CI: 0.2-0.7, P = 0.005). CONCLUSIONS: Reported mould, water damage, and mouldy odours were associated with elevated levels of indoor fungi. However, inaccuracy was high and there was evidence of a systematic reporting bias. Future research should concentrate on developing accurate objective measures of exposure to fungi, and then use this information to develop valid questionnaires. Currently, objective measures not questionnaires, are recommended to clarify the health effects of indoor fungi.     

Rheology of flexible PVC compounds. Part I: The influence of resin crystallinity

The changes occurring in torque during PVC processing in a torque rheometer have been interpreted in terms of the destruction of the supramolecular structure followed by a fusion of the grain fragments. In contrast to changes in torque, changes in elasticity occur in the absence of grain breakdown. It is proposed that the change in elasticity during processing is the result of changing crystallinity of the resin. In the early stages of processing, crystallites melt and elasticity decreases. As grains fuse together, new crystallites are formed in the previously unoccupied grain boundaries and the elasticity increases.     

A novel direct aerodynamically assisted threading methodology for generating biologically viable microthreads encapsulating living primary cells

In a recent discovery, coaxial electrospinning was explored to encapsulate living organisms within a continuous bio‐polymeric microthread from which active biological scaffolds were fabricated (Townsend‐Nicholson and Jayasinghe, Biomacromolecules 2006, 7, 3364). The cells were demonstrated to have gone through all expected cellular activity without their viability being compromised. These biologically active threads and scaffolds have direct and tremendous applicability from regenerative to therapeutic medicine. Currently these post‐processed cells as composite threads and scaffolds are being investigated in‐depth at a cellular level to establish if the processing methodology has any affect on the cellular make‐up. We now demonstrate a competing non‐electric field driven approach for fabricating composite threads and scaffolds influenced only by a differential pressure. We refer to this novel composite thread to scaffold fabrication methodology as coaxial aerodynamically assisted bio‐threading (CAABT). Our investigations firstly, demonstrate that this technique can process handle living organisms without biologically perturbing them in anyway. Secondly the process is elucidated as possessing the ability to form composite active threads from which biologically viable scaffolds are formed. Finally our study employs florescent activated cell sorting (FACScan), a method by which the cellular dynamics and viability are quantified on control and threaded cellular samples at two prescribed time points. In parallel with FACScan, optical comparison of cellular morphology at three time points within a period of three weeks is carried out to photographically observe any changes in the post‐processed cellular phenotype. Our developmental investigations into this novel aerodynamically assisted threading methodology has unearthed a unique biomicrofabrication approach, which joins cell electrospinning in the cell threading to scaffold fabrication endeavor. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Why do fish strand? An analysis of ten years of flow reduction monitoring data from the Columbia and Kootenay rivers,Canada

Stranding of fish due to flow reductions has been documented in the near shore of the Columbia and Kootenay Rivers, Canada, and can result in sub‐lethal or lethal effects on fish. Ten years (1999–2009) of monitoring data have been collected at sites below two hydro‐electric dams (Hugh‐L‐Keenleyside and Brilliant Dam) following flow reductions. A generalized linear mixed effects model analysed the probability of a stranding event in relation to environmental and operational variables including the rate of change in the water levels, the duration of shoreline inundation prior to a reduction (wetted history), the river stage, the magnitude of the reduction, distance downstream from the dam, time of day, day of year (season) and whether a site had been physically altered to mitigate stranding. The results demonstrated statistically significant effects on stranding risk from minimum river stage, day of the year and whether a site had been physically re‐contoured. The combination of investigated factors giving the highest probability of stranding was a large magnitude reduction completed in the afternoon in midsummer, at low water levels when the near shore had been inundated for a long period. This research is significant in its approach to assessing years of ecosystem scale monitoring data and using the modelling results to determine ways for these findings to be applied in regulated river management to minimize fish stranding. It also highlighted data gaps that require addressing and provides ecosystem scale results to compare with stranding studies carried out in mesocosms. © 2014 The Authors. River Research and Applications published by John Wiley & Sons Ltd.