Characterization of a Novel Mouse Model of Multiple Myeloma and Its Use in Preclinical Therapeutic Assessment

To aid preclinical development of novel therapeutics for myeloma, an in vivo model which recapitulates the human condition is required. An important feature of such a model is the interaction of myeloma cells with the bone marrow microenvironment, as this interaction modulates tumour activity and protects against drug-induced apoptosis. Therefore NOD/SCIDγc^null mice were injected intra-tibially with luciferase-tagged myeloma cells. Disease progression was monitored by weekly bioluminescent imaging (BLI) and measurement of paraprotein levels. Results were compared with magnetic resonance imaging (MRI) and histology. Assessment of model suitability for preclinical drug testing was investigated using bortezomib, melphalan and two novel agents. Cells engrafted at week 3, with a significant increase in BLI radiance occurring between weeks 5 and 7. This was accompanied by an increase in paraprotein secretion, MRI-derived tumour volume and CD138 positive cells within the bone marrow. Treatment with known anti-myeloma agents or novel agents significantly attenuated the increase in all disease markers. In addition, intra-tibial implantation of primary patient plasma cells resulted in development of myeloma within bone marrow. In conclusion, using both myeloma cell lines and primary patient cells, we have developed a model which recapitulates human myeloma by ensuring the key interaction of tumour cells with the microenvironment.     

β-D-galactosidase activity of viable, non-culturable coliform bacteria in marine waters

The β-D-galactosidase activity of viable but non-culturable (vnc) Escherichia coli cells in seawater was investigated using a rapid fluorimetric enzyme assay. Results from microcosm studies showed that loss of culturability did not necessarily result in loss of the ability to produce the galactosidase enzyme. Even when no culturable cells were detected, a positive enzyme assay response was observed and the activity of the inducible enzyme over time more closely reflected the number of vnc cells present.     

Regulation of Rat Dopamine Transporter mRNA and Protein by Chronic Cocaine Administration

This study describes a direct comparison of dopamine transporter (DAT) mRNA and protein, as well as its binding sites, in tissue from the same animals after chronic cocaine administration. Rats were treated twice daily with 25 mg/kg cocaine or with saline. After 8 days of cocaine administration, changes in DAT mRNA levels in the substantia nigra pars compacta and ventral tegmental area were measured by in situ hybridization, and DAT protein in the striatum was quantified by immunoblotting. Whereas chronic cocaine treatment significantly reduced levels of DAT mRNA in the substantia nigra pars compacta and ventral tegmental area as compared with vehicle-treated controls, cocaine treatment did not alter DAT protein levels in the striatum. Furthermore, the density of DAT binding sites was also measured in the striatum by quantitative autoradiography using two DAT radioligands, 33-(4-[125I]iodophenyl)tropane-2-carboxylic acid methyl ester ([125I]RTI-55) and [3H]propanoyl-3beta-(4-tolyl)tropane ([3H]PTT). Similar to the results of immunoblotting of DAT protein, [1251]RTI-55 and [3H]PTT binding site levels also remained unaltered. These results indicate a dissociation in the regulation of DAT mRNA and its protein levels as a result of cocaine administration in rats. This study also indicates that the DAT ligands [3H]PTT and [125I]RTI-55 provide an accurate assessment of DAT protein levels.     

False Memory ≠ False Memory: DRM Errors Are Unrelated to the Misinformation Effect

The DRM method has proved to be a popular and powerful, if controversial, way to study ‘false memories’. One reason for the controversy is that the extent to which the DRM effect generalises to other kinds of memory error has been neither satisfactorily established nor subject to much empirical attention. In the present paper we contribute data to this ongoing debate. One hundred and twenty participants took part in a standard misinformation effect experiment, in which they watched some CCTV footage, were exposed to misleading post-event information about events depicted in the footage, and then completed free recall and recognition tests. Participants also completed a DRM test as an ostensibly unrelated filler task. Despite obtaining robust misinformation and DRM effects, there were no correlations between a broad range of misinformation and DRM effect measures (mean r  = −.01). This was not due to reliability issues with our measures or a lack of power. Thus DRM ‘false memories’ and misinformation effect ‘false memories’ do not appear to be equivalent.