Localization by immunoelectron microscopy of Schistosoma mansoni antigens in the glomerulus of the hamster (Mesocricetus auratus) kidney

Gene therapy has the potential to provide cancer treatments based on novel mechanisms of action with potentially low toxicities. This therapy may provide more effective control of loco-regional recurrence in diseases such as non-small cell lung cancer (NSCLC), as well as systemic control of micrometastases. Despite current limitations, retroviral and adenoviral vectors can in certain circumstances provide an effective means of delivering therapeutic genes to tumour cells. Although multiple genes are involved in the process of carcinogenesis, mutations of the p53 gene are the most frequent abnormality identified in human tumours. Pre-clinical studies both in vitro and in vivo have shown that restoration of p53 function can induce apoptosis in cancer cells. Phase I clinical trials now show that p53 gene replacement therapy is feasible and safe using both retroviral and adenoviral vectors, and that it induces tumour regression in patients with advanced NSCLC and recurrent head and neck cancer. Other pre-clinical studies indicate that gene therapy may have useful synergy with cytotoxic and radiation therapy. This paper describes the different gene therapy strategies under investigation and the pre-clinical data that provides a rationale for the gene replacement approach, reviews clinical trial data and presents novel ideas for improving current vectors and gene delivery to tumours.     

Superior vena cava syndrome after heart transplantation: percutaneous treatment of a complication of bicaval anastomoses

The aims of this study were to establish a working rabbit heart model of regional myocardial ischaemia in which electrophysiologic parameters and arrhythmogenesis could be correlated and to explore the mechanisms underlying the antiarrhythmic activity of lignocaine. Monophasic action-potential duration (MAPD90), effective refractory period (ERP), and conduction delay were measured at three ventricular sites in isolated hearts paced at 3.3 Hz. The hearts were treated before and throughout 30 min of ischaemia and 15 min of reperfusion with a vehicle or 20 microM lignocaine. In both groups, ischaemia produced a similar shortening in MAPD90. Lignocaine decreased ERP shortening during ischaemia from -56+/-4 to -32+/-6 ms. An ischaemia-induced increase in conduction delay was greater in the lignocaine than the control group (49+/-7 vs. 11+/-2 ms). Ischaemia-induced dispersion of repolarisation was reduced by lignocaine from 66+/-4 to 32+/-7 ms, and dispersion of refractoriness was decreased from 57+/-6 to 16+/-3 ms. Lignocaine decreased inducibility of ventricular fibrillation (VF) during ischaemia from 86 to 25%. We conclude that, in this model, the antiarrhythmic activity of lignocaine during regional ischaemia is associated with an increase in ischaemia-induced conduction delay and reduced dispersion of repolarisation and refractoriness.     

Iterative multi-party agreement negotiation for establishing collaborations

Inter-domain collaborations suffer not only from technological obstacles that hinder interoperability, but also from diverting business objectives of the involved domains. Today, hand-crafted contracts define the terms and conditions for service interactions. Electronic negotiation can serve as the enabler of dynamic interdomain collaborations by providing a large degree of freedom for the automation of agreement formation and electronic contracting. Negotiation by electronic means has been an area of intensive research for many years now. However, most effort was put on the determination of prices and neglected that real-world agreements also consist of complex dependencies of interdependent obligations. In this paper we present agreement negotiation as a tool to establish ad hoc services collaborations. Our novel protocol allows for the discovery of complex agreement options and for the formation of multi-party agreements. The protocol works through an iterative exchange of requirements and offers. A major benefit over existing bilateral negotiation protocols is that our protocol is capable of discovering potential collaborations between different parties. It will leave each negotiating party with a complete agreement document after a successful negotiation. This comprehensive agreement document defines the interdependent obligations between all parties and is well suited for E-Contracting.     

The "first generation" of endovascular stent-grafts for patients with aneurysms of the descending thoracic aorta

OBJECTIVE: Our goal was to determine whether endovascular stent-grafting is feasible and effective for patients with aneurysms of the descending thoracic aorta. METHODS: Starting in July 1992, we conducted a prospective, uncontrolled clinical trial in 103 patients (mean age 69 years [range 34-89 years]) who underwent endovascular treatment of aneurysms of the descending thoracic aorta using a custom-fabricated, self-expanding stent-graft device. Follow-up was 100% complete and averaged 22 months. Sixty-two patients (60%) were judged not to be reasonable candidates for a conventional "open" surgical procedure. RESULTS: Complete thrombosis of the aneurysm was ultimately achieved in 86 (83%) patients. The early mortality rate was 9% +/- 3% (+/- 70% CL). Multivariable analysis revealed that myocardial infarction or stroke was linked with a higher likelihood of early death (P = .001). Early serious complications included paraplegia in 3% +/- 2% and stroke in 7% +/- 3%. Actuarial survival estimates at 1 year and 2 years were 81% +/- 4% and 73% +/- 5% (+/- 1 SE), respectively; being judged not to be a surgical candidate portended a higher probability of death (P = .003). According to the intent-to-treat principle, "treatment failure" (including all late sudden unexplained deaths) occurred in 38 patients; 53% +/- 10% of patients were free from treatment failure at 3.7 years. Stent-graft related complications occurred commonly and were linked with several anatomic, technical, and patient-related risk factors. CONCLUSIONS: This 5-year clinical trial involving use of a "first generation" device indicates that endovascular stent-grafting of descending thoracic aortic aneurysms is feasible with acceptable medium-term results. More refined, commercially developed devices available today offer less traumatic and more precise stent-graft deployment; these major technical advantages, coupled with important lessons we have learned over time and better patient selection, should be associated with more salutary clinical results in the future.     

Use of subjective and nonsubjective methodologies to evaluate lens radiation damage in exposed populations--an overview

The general epidemiological acceptability of prevalence, or incidence, for assessing risk of radiation cataract development has dictated an almost exclusive dependence on cataract onset as a measure of cataractogenicity for given doses of radiation. The advent of instrumentation capable of acquiring images amenable to quantitative analyses offers the possibility of exploiting "relative opacification" as an added, if not exclusive, parameter. This development is particularly important in efforts to assess populations such as that in the Altai, which are temporally far removed from their exposure and among whom there exists a large subset with extant cataracts. The new technologies, Scheimpflug and retroillumination imaging, combined with the application of the appropriate analytical algorithms can not only provide quantitative and nonsubjective assessment of lens transparency, but also serve as a means to immortalize the state of the pathology at the time of acquisition. Highly relevant to the assessment of an aging exposed population is the use of lens epithelial fragments as potential dosimeters. The material is routinely available as a result of cataract extraction procedures and is amenable to the application of a modified micronucleus (MN) assay. The MN assay in the lens has tremendous advantages over its use in other tissues for a number of reasons, not least of which is that lens MNs are extremely long-lived. Given the relative ease of application and its potential as a radiation bioindicator, the lens MN assay should be considered in any follow-up of populations exposed to ionizing radiation.     

The effect of climate variations on glulam—an experimental study

Climate variations affect timber structures by causing moisture induced stresses which may lead to cracks in timber members. The paper presents experimentally determined moisture induced stresses that arise perpendicular to the grain of glulam specimens during exposure to 1-dimensional drying and wetting. Although to a certain extent reduced by creep effects, the determined tensile stresses can significantly exceed the characteristic tensile strength of glulam. Additional measurements of moduli of elasticity (E) and hygroexpansion coefficients (α) revealed that these parameters are strongly affected by the geometrical configuration (pith locations) of the specimens. By means of all the parameters determined here, it can be avoided that parameters have to be selected from different literature sources, which introduces large uncertainties into the numerical simulations.     

Determinant spreading associated with demyelination in a nonhuman primate model of multiple sclerosis

Definition of the immune process that causes demyelination in multiple sclerosis is essential to determine the feasibility of Ag-directed immunotherapy. Using the nonhuman primate, Callithrix jacchus jacchus (common marmoset), we show that immunization with myelin basic protein and proteolipid protein determinants results in clinical disease with significant demyelination. Demyelination was associated with spreading to myelin oligodendrocyte glycoprotein (MOG) determinants that generated anti-MOG serum Abs and Ig deposition in central nervous system white matter lesions. These data associate intermolecular "determinant spreading" with clinical autoimmune disease in primates and raise important issues for the pathogenesis and treatment of multiple sclerosis.