Cathepsin S expression: An independent prognostic factor in glioblastoma tumours - A pilot Study

Cysteine proteinases have been implicated in astrocytoma invasion. We recently demonstrated that cathepsin S (CatS) expression is up-regulated in astrocytomas and provided evidence for a potential role in astrocytoma invasion (Flannery et al., Am J Path 2003;163(1):175–82). We aimed to evaluate the significance of CatS in human astrocytoma progression and as a prognostic marker. Frozen tissue homogenates from 71 patients with astrocytomas and 3 normal brain specimens were subjected to ELISA analyses. Immunohistochemical analysis of CatS expression was performed on 126 paraffin-embedded tumour samples. Fifty-one astrocytoma cases were suitable for both frozen tissue and paraffin tissue analysis. ELISA revealed minimal expression of CatS in normal brain homogenates. CatS expression was increased in grade IV tumours whereas astrocytoma grades I–III exhibited lower values. Immunohistochemical analysis revealed a similar pattern of expression. Moreover, high-CatS immunohistochemical scores in glioblastomas were associated with significantly shorter survival (10 vs. 5 months, p = 0.014). With forced inclusion of patient age, radiation dose and Karnofsky score in the Cox multivariate model, CatS score was found to be an independent predictor of survival. CatS expression in astrocytomas is associated with tumour progression and poor outcome in glioblastomas. CatS may serve as a useful prognostic indicator and potential target for anti-invasive therapy.

Positronium scattering by Ne, Ar, Kr and Xe in the frozen target approximation

A full-electron coupled-state treatment of positronium (Ps)- inert gas scattering is developed within the context of the frozen target approximation. Calculations are performed for Ps(Is) scattering by Ne and Ar in the impact energy range 0-40 eV using coupled pseudostate expansions consisting of nine and 22 Ps states. The purpose of the pseudostates is primarily to represent ionization of the Ps which is found to be a major process at the higher energies. First Born estimates of target excitation are used to complement the frozen target results. The available experimental data are discussed in detail. It is pointed out that the very low energy measurements (less than or equal to2 eV) correspond to the momentum transfer cross section sigma(mom) and not to the elastic cross section sigma(el). Calculation shows that sigma(mom), and sigma(el) diverge very rapidly with increasing energy and consequently comparisons of the low-energy data with ITel can be very misleading. Agreement between the calculations and the low-energy measurements of anion as well;as higher energy (greater than or equal to15 eV) beam measurements of the total cross section, is less than satisfactory. Results for Ps(1s) scattering by Kr and Xe in the static-exchange approximation are also presented.

Ionization energies of beryllium in strong magnetic fields: a frozen core approximation

An effective frozen core approximation has been developed and applied to the calculation of energy levels and ionization energies of the beryllium atom in magnetic field strengths up to 2.35 x 10(5) T. Systematic improvement over the existing results for the beryllium ground and low-lying states has been accomplished by taking into account most of the correlation effects in the four-electron system. To our knowledge, this is the first calculation of the electronic properties of the beryllium atom in a strong magnetic field carried out using a configuration interaction approximation and thus allowing a treatment beyond that of Hartree-Fock. Differing roles played by strong magnetic fields in intrashell correlation within different states are observed. In addition, possible ways to gain further improvement in the energies of the states of interest are proposed and discussed briefly.

Isolation and cloning of exendin precursor cDNAs from single samples of venom from the Mexican beaded lizard (Heloderma horridum) and the Gila Monster (Heloderma suspectum)

Reptile venoms are complex cocktails of bioactive molecules, including peptides. While the drug discovery potential of most species remains unrealized, many are endangered and afforded protection under international treaties. In this study, we describe how potential clinically important bioactive peptides and their corresponding mRNAs can be structurally characterized from single, small samples of reptile venom. The potential type-2 diabetes therapeutics, exendin-3 and exendin-4, from the Mexican beaded lizard (Heloderma horridum) and the Gila monster (Heloderma suspectum), respectively, have been characterized at both protein and nucleic acid levels to illustrate the efficacy of the technique and its contribution to biodiversity conservation.

The use of Raman microscopy to determine and localize vitamin E in biological samples

Alpha-tocopherol (aT), the predominant form of vitamin E in mammals, is thought to prevent oxidation of polyunsaturated fatty acids. In the lung, aT is perceived to be accumulated in alveolar type II cells and secreted together with surfactant into the epithelial lining fluid. Conventionally, determination of aT and related compounds requires extraction with organic solvents. This study describes a new method to determine and image the distribution of aT and related compounds within cells and tissue sections using the light-scattering technique of Raman microscopy to enable high spatial as well as spectral resolution. This study compared the nondestructive analysis by Raman microscopy of vitamin E, in particular aT, in biological samples with data obtained using conventional HPLC analysis. Raman spectra were acquired at spatial resolutions of 2-0.8 microm. Multivariate analysis techniques were used for analyses and construction of corresponding maps showing the distribution of aT, alpha-tocopherol quinone (aTQ), and other constituents (hemes, proteins, DNA, and surfactant lipids). A combination of images enabled identification of colocalized constituents (heme/aTQ and aT/surfactant lipids). Our data demonstrate the ability of Raman microscopy to discriminate between different tocopherols and oxidation products in biological specimens without sample destruction. By enabling the visualization of lipid-protein interactions, Raman microscopy offers a novel method of investigating biological characterization of lipid-soluble compounds, including those that may be embedded in biological membranes such as aT.

Performance of clay samples reinforced with vertical granular columns

This paper reports an experimental study in which samples of soft kaolin clay (100 mm in diameter and 200 mm in height) were reinforced with vertical columns of sand and tested under triaxial conditions. Samples were reinforced with either a single column of sand of 32 mm diameter or three columns of sand, each of 20 mm diameter. The replacement method was used to form the columns. The columns were installed in the clay to depths of 120 and 200 mm. Tests were also carried out on samples that were not reinforced with sand columns. The samples were compressed under both drained and undrained conditions. It was found that the undrained shear strength of samples containing full-depth columns was greatly improved compared with that of the unreinforced samples. In the fully drained tests, the sample installed with a single column of 32 mm diameter exhibited better performance than the sample with three columns of 20 mm diameter, although the area replacement ratio in the case of the three 20 mm diameter columns was higher than that of the single 32 mm diameter column. However, the undrained strength of the composite material was not particularly affected by the number of columns.