Matrix metalloproteinase-2 and-9 involvement in canine tumors

Matrix metalloproteinases (MMPs) are a family of enzymes implicated in the degradation and remodeling of extracellular matrix and in vascularization. They are also involved in pathologic processes such as tumor invasion and metastasis in experimental cancer models and in human malignancies. We used gelatin zymography and inummohistochemistry to determine whether MMP-2 and MMP-9 are present in canine tumors and normal tissues and whether MMP production correlates with clinicopathologic parameters of prognostic importance. High levels of pro-MMP-9, pro-MMP-2, and active MMP-2 were detected in most canine tumors. Significantly higher MMP levels were measured in canine tumors than in nontumors, malignancies had higher MMP levels than benign tumors, and sarcomas had higher active MMP-2 than carcinomas. Cartilaginous tumors produced higher MMP levels than did nonsarcomatous malignancies, benign tumors, and normal tissues, and significantly greater MMP-2 than osteosarcomas and fibrosarcomas. Pro-MMP-9 production correlated with the histologic grade of osteosarcomas. The 62-kd form of active MMP-2 was detected only in high-grade, p53-positive, metastatic malignancies. Zymography proved to be a sensitive and quantitative technique for the assessment of MMP presence but has the limitation of requiring fresh tissue; inummohistochemistry is qualitative and comparatively insensitive but could be of value in archival studies. MMP presence was shown in a range of canine tumors, and their link to tumor type and grade was demonstrated for the first time. This study will allow a substantially improved evaluation of veterinary cancer patients and provides baseline information necessary for the design of clinical trials targeting MMPs.

Fatty acid binding protein is a major determinant of hepatic pharmacokinetics of palmitate and its metabolites

Disposition kinetics of [H-3] palmitate and its low-molecular-weight metabolites in perfused rat livers were studied using the multiple-indicator dilution technique, a selective assay for [H-3] palmitate and its low-molecular-weight metabolites, and several physiologically based pharmacokinetic models. The level of liver fatty acid binding protein (L-FABP), other intrahepatic binding proteins (microsomal protein, albumin, and glutathione S-transferase) and the outflow profiles of [H-3] palmitate and metabolites were measured in four experimentalgroups of rats: 1) males; 2) clofibrate-treated males; 3) females; and 4) pregnant females. A slow-diffusion/bound model was found to better describe the hepatic disposition of unchanged [H-3] palmitate than other pharmacokinetic models. The L-FABP levels followed the order: pregnant female > clofibrate-treated male > female > male. Levels of other intrahepatic proteins did not differ significantly. The hepatic extraction ratio and mean transit time for unchanged palmitate, as well as the production of low-molecular-weight metabolites of palmitate and their retention in the liver, increased with increasing L-FABP levels. Palmitate metabolic clearance, permeability-surface area product, retention of palmitate by the liver, and cytoplasmic diffusion constant for unchanged [H-3] palmitate also increased with increasing L-FABP levels. It is concluded that the variability in hepatic pharmacokinetics of unchanged [H-3] palmitate and its low-molecular-weight metabolites in perfused rat livers is related to levels of L-FABP and not those of other intrahepatic proteins.

Model-based analysis of anaerobic acetate uptake by a mixed culture of polyphosphate-accumulating and glycogen-accumulating organisms

An increasing number of studies shows that the glycogen-accumulating organisms (GAOs) can survive and may indeed proliferate under the alternating anaerobic/aerobic conditions found in EBPR systems, thus forming a strong competitor of the polyphosphate-accumulating organisms (PAOs). Understanding their behaviors in a mixed PAO and GAO culture under various operational conditions is essential for developing operating strategies that disadvantage the growth of this group of unwanted organisms. A model-based data analysis method is developed in this paper for the study of the anaerobic PAO and GAO activities in a mixed PAO and GAO culture. The method primarily makes use of the hydrogen ion production rate and the carbon dioxide transfer rate resulting from the acetate uptake processes by PAOs and GAOs, measured with a recently developed titration and off-gas analysis (TOGA) sensor. The method is demonstrated using the data from a laboratory-scale sequencing batch reactor (SBR) operated under alternating anaerobic and aerobic conditions. The data analysis using the proposed method strongly indicates a coexistence of PAOs and GAOs in the system, which was independently confirmed by fluorescent in situ hybridization (FISH) measurement. The model-based analysis also allowed the identification of the respective acetate uptake rates by PAOs and GAOs, along with a number of kinetic and stoichiometric parameters involved in the PAO and GAO models. The excellent fit between the model predictions and the experimental data not involved in parameter identification shows that the parameter values found are reliable and accurate. It also demonstrates that the current anaerobic PAO and GAO models are able to accurately characterize the PAO/GAO mixed culture obtained in this study. This is of major importance as no pure culture of either PAOs or GAOs has been reported to date, and hence the current PAO and GAO models were developed for the interpretation of experimental results of mixed cultures. The proposed method is readily applicable for detailed investigations of the competition between PAOs and GAOs in enriched cultures. However, the fermentation of organic substrates carried out by ordinary heterotrophs needs to be accounted for when the method is applied to the study of PAO and GAO competition in full-scale sludges. (C) 2003 Wiley Periodicals, Inc.

Metabolic model for glycogen-accumulating organisms in anaerobic/aerobic activated sludge systems

Glycogen-accumulating organisms (GAO) have the potential to directly compete with polyphosphate-accumulating organisms (PAO) in EBPR systems as both are able to take up VFA anaerobically and grow on the intracellular storage products aerobically. Under anaerobic conditions GAO hydrolyse glycogen to gain energy and reducing equivalents to take up VFA and to synthesise polyhydroxyalkanoate (PHA). In the subsequent aerobic stage, PHA is being oxidised to gain energy for glycogen replenishment (from PHA) and for cell growth. This article describes a complete anaerobic and aerobic model for GAO based on the understanding of their metabolic pathways. The anaerobic model has been developed and reported previously, while the aerobic metabolic model was developed in this study. It is based on the assumption that acetyl-CoA and propionyl-CoA go through the catabolic and anabolic processes independently. Experimental validation shows that the integrated model can predict the anaerobic and aerobic results very well. It was found in this study that at pH 7 the maximum acetate uptake rate of GAO was slower than that reported for PAO in the anaerobic stage. On the other hand, the net biomass production per C-mol acetate added is about 9% higher for GAO than for PAO. This would indicate that PAO and GAO each have certain competitive advantages during different parts of the anaerobic/aerobic process cycle. (C) 2002 Wiley Periodicals, Inc.

Dehydration converts DsbG crystal diffraction from low to high resolution

Diffraction quality crystals are essential for crystallographic studies of protein structure, and the production of poorly diffracting crystals is often regarded as a dead end in the process. Here we show a dramatic improvement of poorly diffracting DsbG crystals allowing high-resolution diffraction data measurement. Before dehydration, the crystals are fragile and the diffraction pattern is streaky, extending to 10 Angstrom resolution. After dehydration, there is a spectacular improvement, with the diffraction pattern extending to 2 Angstrom resolution. This and other recent results show that dehydration is a simple, rapid, and inexpensive approach to convert poor quality crystals into diffraction quality crystals.

Interleukin 2 production, not the pattern of early T-cell antigen receptor-dependent tyrosine phosphorylation, controls anergy induction by both agonists and partial agonists.

Full activation of T cells requires signaling through the T-cell antigen receptor (TCR) and additional surface molecules interacting with ligands on the antigen-presenting cell. TCR recognition of agonist ligands in the absence of accessory signals frequently results in the induction of a state of unresponsiveness termed anergy. However, even in the presence of costimulation, anergy can be induced by TCR partial agonists. The unique pattern of early receptor-induced tyrosine phosphorylation events induced by partial agonists has led to the hypothesis that altered TCR signaling is directly responsible for the development of anergy. Here we show that anergy induction is neither correlated with nor irreversibly determined by the pattern of early TCR-induced phosphorylation. Rather, it appears to result from the absence of downstream events related to interleukin 2 receptor occupancy and/or cell division. This implies that the anergic state can be manipulated independently of the precise pattern of early biochemical changes following TCR occupancy, a finding with implications for understanding the induction of self-tolerance and the use of partial agonist ligands in the treatment of autoimmune diseases.

Harrison's Analytical digest of all the reported cases determined in the House of lords, the several courts of common law, in banc and nisi prius, and the Court of bankruptcy: from Michaelmas term, 1856, to Easter term 1843; including also the crown cases reserved, and a full selection of equity decisions: with the manuscript cases cited in the best modern treaties not elsewhere reported: to which is added a Supplement continuing work to the year 1846.

Mode of access: Internet.

Valerian does not appear to reduce symptoms for patients with chronic insomnia in general practice using a series of randomised n-of-I trials

Objectives: To investigate the effectiveness of valerian for the management of chronic insomnia in general practice. Design: Valerian versus placebo in a series of n-of-1 trials, in Queensland, Australia. Results: Of 42 enrolled patients, 24 (57%) had sufficient data for inclusion into the n-of-1 analysis. Response to valerian was fair for 23 (96%) participants evaluating their 'energy level in the previous day' but poor or modest for all 24 (100%) participants' response to 'total sleep time' and for 23 (96%) participants' response to 'number of night awakenings' and 'morning refreshment'. As a group, the proportion of treatment successes ranged from 0.35 (95% CI 0.23, 0.47) to 0.55 (95% CI 0.43, 0.67) for the six elicited outcome sleep variables. There was no significant difference in the number (P = 0.06), distribution (P = 1.00) or severity (P = 0.46) of side effects between valerian and placebo treatments. Conclusions: Valerian was not shown to be appreciably better than placebo in promoting sleep or sleep-related factors for any individual patient or for all patients as a group. (C) 2003 Elsevier Ltd. All rights reserved.

Rapid manufacturing of aluminum components

A manufacturing technique for the production of aluminum components is described. A resin-bonded part is formed by a rapid prototyping technique and then debound and infiltrated by a second aluminum alloy under a nitrogen atmosphere. During thermal processing, the aluminum reacts with the nitrogen and is partially transformed into a rigid aluminum nitride skeleton, which provides the structural rigidity during infiltration. The simplicity and rapidity of this process in comparison to conventional production routes, combined with the ability to fabricate complicated parts of almost any geometry and with high dimensional precision, provide an additional means to manufacture aluminum components.

Social indicators and comparisons of living standards

Construction of an international index of standards of living, incorporating social indicators and economic output, typically involves scaling and weighting procedures that lack welfare-economic foundations. Revealed preference axioms can be used to make quality-of-life comparisons if we can estimate the representative household's production technology for the social indicators. This method is applied to comparisons of gross domestic product (GDP) and life expectancy for 58 countries. Neither GDP rankings, nor the rankings of the Human Development Index (HDI), are consistent with the partial ordering of revealed preference. A method of constructing a utility-consistent index incorporating both consumption and life expectancy is suggested. (C) 2003 Elsevier Science B.V. All rights reserved.

All's fair in love and war - but not contract

Changes to Queensland's unfair terms in consumer contracts expected - nature of the changes outlined - protections given to consumers, with respect to unfair contracts, in Victoria and the United Kingdom.

On the role of tin in the infiltration of aluminium by aluminium for rapid prototyping applications

The use of tin as an alloying element in the production of freeformed infiltrated aluminium components is explored. Tin slows the growth of the aluminium nitride skeleton which provides dimensional stability, as well as increasing the rate of infiltration of the aluminium liquid into the aluminium nitride skeleton. (C) 2004 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Performance of improved guayule lines in Australia

Guayule (Parthenium argentatum Gray) is a potential source of commercial natural rubber. Its commercialisation depends mainly on economical plant production. The objective of this study was to evaluate the performance of improved lines in Australia. Seeds from five improved lines (AZ-1, AZ-2, AZ-3, AZ-5 and AZ-6) and two previously developed guayule lines (N 565 and 11591) were obtained from the Agricultural Research Service (ARS) of the United States Department of Agriculture (USDA). Seedlings from these lines were grown in a glasshouse for 3 months and later transplanted in a field experiment in early September 2001. Plant height and width were monitored from transplanting to 62 weeks at regular intervals. After 62 weeks, plant dry matter production, rubber and resin content, and yields were analysed. Plant height and width of the improved lines were higher than N 565 and 11591. Plant dry matter, rubber and resin yields were significantly different among lines. Of the five lines, AZ-1 and AZ-2 produced rubber yields of 620 and 550 kg/ha, respectively and these yields were significantly greater than for N 565 (371 kg/ha) and 11591 (391 kg/ha). AZ-1 and AZ-2 also produced significantly higher resin yields, 727 and 668 kg/ha, respectively, than those for N 565 (436 kg/ha) and 11591 (325 kg/ha). Rubber and resin yield increase of lines, AZ-1 and AZ-2, were in the range of 41-68% and 53-123%, respectively over N 565 and 11591. AZ-1 tended to produce higher rubber and resin yields than AZ-2 but exhibited highly variable plant height (CV = 25%) and width (CV = 41%) indicating potential for further genetic improvement. AZ-2 offers the best combination of desirable characters including early vigour, uniformity and comparatively higher rubber and resin yields. (C) 2003 Published by Elsevier B.V.