Regional approach to building operational level capacity for disaster planning: the case of the Eastern Africa region.

BACKGROUND: The Eastern Africa region is regularly affected by a variety of disasters ranging from drought, to human conflict and population displacement. The magnitude of emergencies and response capacities is similar across the region. In order to strengthen public health disaster management capacities at the operational level in six countries of the Eastern Africa region, the USAID-funded leadership project worked through the HEALTH Alliance, a network of seven schools of public health from six countries in the region to train district-level teams. OBJECTIVES: To develop a sustainable regional approach to building operational level capacity for disaster planning. METHODS: This project was implemented through a higher education leadership initiative. Project activities were spear-headed by a network of Deans and Directors of public health schools within local universities in the Eastern Africa region. The leadership team envisioned a district-oriented systems change strategy. Pre-service and in-service curricula were developed regionally and district teams were formed to attend short training courses. Project activities began with a situational analysis of the disaster management capacity at national and operational levels. The next steps were chronologically the formation of country training teams and training of trainers, the development of a regional disaster management training curriculum and training materials, the cascading of training activities in the region, and the incorporation of emerging issues into the training curriculum. An evaluation model included the analysis of preparedness impact of the training program. RESULTS: The output from the district teams was the creation of individual district-level disaster plans and their implementation. This 4-year project focused on building operational level public health emergency response capacity, which had not previously been part of any national program. Use of the all-hazard approach rather than a scenario-based contingency planning led to the development of a standardized curriculum for training both in-service and pre-service personnel. Materials developed during the implementation phases of the project have been incorporated into public health graduate curricula in the seven schools. This systems-based strategy resulted in demonstrable outcomes related to district preparedness and university engagement in disaster management. CONCLUSION: University partnerships are an effective method to build district-level disaster planning capacity. Use of a regional network created a standardized approach across six countries.

Fostriecin: chemistry and biology.

A review of the current status of the chemistry and biology of fostriecin (CI-920) is provided. Fostriecin is a structurally unique, naturally-occurring phosphate monoester that exhibits potent and efficacious antitumor activity. Initially it was suggested that its activity could be attributed to a direct, albeit weak, inhibition of the enzyme topoisomerase II. However, recent studies have shown that fostriecin inhibits the mitotic entry checkpoint through the much more potent and selective inhibition of protein phosphatase 2A (PP2A) and protein phosphatase 4 (PP4). In fact, it is the most selective small molecule inhibitor of a protein phosphatase disclosed to date. The contribution, if any, that topoisomerase II versus PP2A/PP4 inhibition makes to fostriecin's antitumor activity has not yet been fully defined. Initial phase I clinical trials with fostriecin never reached dose-limiting toxicity or therapeutic dose levels and were halted due to its storage instability and unpredictable chemical purity. Hence, the total synthesis of fostriecin has been pursued in order to confirm its structure and stereochemistry, to provide access to quantities of the pure natural product, and to access key partial structures or simplified/stable analogs. Several additional natural products have been isolated which contain similar structural features (phospholine, phoslactomycins, phosphazomycin, leustroducsins, sultriecin, and cytostatin), and some exhibit comparable biological properties.

RNA hairpin loops repress protein synthesis more strongly than hammerhead ribozymes.

A general study has been carried out to determine how well hammerhead ribozymes might reduce levels of specific protein synthesis in living cells, compared with RNA hairpin loops as stable but noncleaving controls. Four different experiments are described. First, a wide variety of hammerhead ribozymes, as well as hairpin loops, was cloned into a gene-expression cassette for beta-galactosidase, upstream of the coding sequences for that reporter gene, and expressed from plasmids in several strains of Escherichia coli. The results show that ribozymes, when acting intramolecularly in E. coli, do not significantly reduce the amount of protein synthesized from any construct. As a control, long RNA hairpin loops do greatly reduce the amount of protein made. Secondly, we studied the transcription-translation of these same plasmids in a cell extract from E. coli. Once again, hammerhead ribozymes show no effect on levels of beta-galactosidase, whereas long RNA hairpin loops produce a strong reduction, by apparent attentuation at the level of translation. Thirdly, we added an SV40 promoter to each plasmid, in order to study the effects of these gene-regulators on protein synthesis in Chinese hamster ovary cells. Here active intramolecular ribozymes produce a slight reduction in beta-galactosidase, whereas long RNA hairpin loops produce an even stronger reduction than before. Those hairpin loops apparently induce degradation of their own mRNA in Chinese hamster ovary cells, by a mechanism not seen in E. coli. Finally, analyses of total RNA by S1-trimming show that hammerhead ribozymes will self-cleave a mRNA by a total of no more than 45-50% in E. coli, compared with 70-80% in vitro. Other analyses using Northern blotting were unable to detect any ribozyme cleavage in E. coli or Chinese hamster ovary cells. In summary, the ability of hammerhead ribozymes to reduce protein synthesis appears weak or nonexistent in all the cellular systems tested. By comparison, long RNA hairpin loops reduce protein synthesis strongly: by an apparent attentuation mechanism in E. coli or by a novel degradation of their own mRNA in Chinese hamster ovary cells.

The rough (ro+) gene as a dominant P-element marker in germ line transformation of Drosophila melanogaster.

We describe a new vector for the P-element-mediated introduction of gene constructs into the germ line of Drosophila melanogaster. The P-element vector carries 6.8 kb of genomic DNA containing the rough gene (ro) from D. melanogaster and a polylinker (MCS) containing ten unique cloning sites. To demonstrate its utility, we have cloned into the MCS of this vector, the firefly luciferase (Luc)-encoding gene (luc) under the control of the D. melanogaster hsp70 promoter and have transformed flies with the resultant P-element. Single insertions of this element, whether in the hemizygous or homozygous condition, completely rescued the ro- mutation and directed heat-inducible synthesis of Luc mRNA and enzyme.

Competition studies with repressors and activators of viral enhancer function in F9 mouse embryonal carcinoma cells.

DNA competition studies have been used to investigate the presence of a repressor of viral enhancer function in F9 mouse embryonal carcinoma cells. The complete polyoma virus enhancer region, cotransfected into F9 cells with the SV40 promoter/enhancer attached to a chloramphenicol acetyl transferase marker gene, induced a small increase in pSV2CAT expression. This can be explained by preferential but weak binding by polyoma sequences of a molecule repressing pSV2CAT transcription. Repressor activity substantially disappeared when the cells were induced to differentiate by retinoic acid. Repressor binding was localised to one half of the polyoma enhancer, but was lost on further fragmentation of this region. It appears that multiple sequence elements may be required for repressor binding and that these are at least partially separable from the complement of elements binding enhancer activating molecules.