Antisense Bcl-2 Oligonucleotide Uptake in Human Transitional Cell Carcinoma.

Objectives; Antisense oligonucleotides (AO) downregulate Bcl-2 protein expression in various tumours if good target cell uptake is achieved. In this study, uptake of FITC labelled AO (FITC-AO) directed at Bcl-2 was examined in; (1) the RT4 bladder tumour cell line (2) normal pig urothelium and (3) human superficial bladder tumours. Methods; In the RT4 cell line, uptake of FITC-AO, FITC-scrambled and FITC-sense oligonucleotides were quantified by flow cytometry at 4h intervals over 24h. Uptake of FITC-AO was assessed in normal pig urothelium by flow cytometry after FITC-AO was infused for 1h. Uptake of FITC AO was assessed in samples from 14 human superficial bladder tumours which were maintained in an ex vivo model. In samples from 6 tumours, uptake at 4h was assessed using fluorescence microscopy. In samples from 8 separate tumours uptake every 4h within the first 24h incubation period was assessed by flow cytometry. Results; In the RT4 cell line the FITC-AO, FITC-scrambled and FITC-sense oligonucleotide uptake was similar. Disaggregated cells from the normal urothelium of the three pigs exhibited 33%, 46%, 51% of cells staining positively for FITC-AO as determined by flow cytometry. All 6 tumour samples had detectable intracellular FITC-AO by fluorescence microscopy at 4h. In the 8 tumours ,examined over the 24h incubation period, there was a range of percentages of positively staining cells. However, most tumours had a monotonic increase in intracellular fluorescence intensity that plateaued 16h post infusion. Conclusion; Antisense Bcl-2 oligonucleotides were readily taken up by superficial bladder cancer cells but the heterogenous uptake in tumour samples needs to be considered when assessing the bioavailability of these drugs.

The rotational broadening of V395 Carinae. Implications on the compact object's mass

Context: The masses previously obtained for the X-ray binary 2S 0921-630 inferred a compact object that was either a high-mass neutron star or low-mass black-hole, but used a previously published value for the rotational broadening (v sin i) with large uncertainties. Aims: We aim to determine an accurate mass for the compact object through an improved measurement of the secondary star's projected equatorial rotational velocity. Methods: We have used UVES echelle spectroscopy to determine the v sin i of the secondary star (V395 Car) in the low-mass X-ray binary 2S 0921-630 by comparison to an artificially broadened spectral-type template star. In addition, we have also measured v sin i from a single high signal-to-noise ratio absorption line profile calculated using the method of Least-Squares Deconvolution (LSD). Results: We determine v sin i to lie between 31.3±0.5 km s-1 to 34.7±0.5 km s-1 (assuming zero and continuum limb darkening, respectively) in disagreement with previous results based on intermediate resolution spectroscopy obtained with the 3.6 m NTT. Using our revised v sin i value in combination with the secondary star's radial velocity gives a binary mass ratio of 0.281±0.034. Furthermore, assuming a binary inclination angle of 75° gives a compact object mass of 1.37±0.13 M_?. Conclusions: We find that using relatively low-resolution spectroscopy can result in systemic uncertainties in the measured v sin i values obtained using standard methods. We suggest the use of LSD as a secondary, reliable check of the results as LSD allows one to directly discern the shape of the absorption line profile. In the light of the new v sin i measurement, we have revised down the compact object's mass, such that it is now compatible with a canonical neutron star mass.

‘The Judiciary and Political Change in Africa: Developing Transitional Jurisprudence in Nigeria’

At a time of increased evaluations of law, human rights, and the rise of judicial power all over the globe, the work of most African judiciaries and the principles of the jurisprudence they espouse in promoting social justice remain an unlikely focus of comparative legal scholarship. This ought not to be so in view of the considerable activities of the courts on the continent in the dawn of the third wave of democratization. This article explores the work of the Nigerian Supreme Court in the political transition to democracy since 1999. Utilizing insights from the work of Ruti Teitel, it attempts to outline some of the major constitutional and extraconstitutional principles adopted by the Court in mediating intergovernmental contestations in the turbulent transition away from almost three decades of authoritarian military rule. It emerges that the task of fostering social transformation through the “weakest” branch seriously tasks the institutional integrity of the judiciary.