Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis

Background The mechanisms responsible for disturbed iron homoeostasis in hereditary haemochromatosis are poorly understood. However, results of some studies indicate a link between hepcidin, a liver-derived peptide, and intestinal iron absorption, suggesting that this molecule could play a part in hepatic iron overload. To investigate this possible association, we studied the hepatic expression of the gene for hepcidin (HAMP) and a gene important in iron transport (IREG1) in patients with haemochromatosis, in normal controls, and in Hfe-knockout mice. Methods We extracted total RNA from the liver tissue of 27 patients with HFE-associated haemochromatosis, seven transplant donors (controls), and Hfe-knockout mice. HAMP and IREG1 mRNA concentrations were examined by ribonuclease protection assays and expressed relative to the housekeeping gene GAPD. Findings There was a significant decrease in HAMP expression in untreated patients compared with controls (5.4-fold, 95% CI 3.3-7.5; p

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.

Sexual dysfunction in the Australian population

AIM: To describe the prevalence and forms of sexual dysfunction experienced by Australians, and compare these with people in the United States. METHODS: A cross sectional, telephone interview survey of a randomly selected sample of men (n = 876) and women (n = 908) aged between 18 and 59 years on the electoral roll in all states and territories of Australia (response rate = 61%) was conducted between November 1999 and April 2000. RESULTS: Large proportions of Australian men (55.0%) and women (60.5%) reported at least one sexual problem within the preceding year. More serious sexual dysfunction (> 3 symptoms) was observed in 13.2% of men and 19.7% of women. DISCUSSION: Australia and the USA are similar with regard to the high rate of symptoms of sexual dysfunction observed in the population. The low rate of treatment points to both patient and doctor reluctance to discuss sexual performance and practices.

Identification and characterization of the hepatic stellate cell transferrin receptor

Activated hepatic stellate cells have been implicated in the fibrogenic process associated with iron overload, both in animal models and in human hemochromatosis. Previous studies have evaluated the role of ferritin/ferritin receptor interactions in the activation of stellate cells and subsequent fibrogenesis; however, the role of transferrin in hepatic stellate cell biology is unknown. This study was designed to identify and characterize the stellate cell transferrin receptor and to evaluate the influence of transferrin on stellate cell activation. Identification and characterization of the stellate cell transferrin receptor was determined by competitive displacement assays. The effect of transferrin on stellate cell activation was assessed using western blot analysis for alpha-smooth muscle actin expression, [H-3]Thymidine incorporation, and real-time RT-PCR for procollagen 1(I) mRNA expression. A specific receptor for rat transferrin was observed on activated but not quiescent stellate cells. Transferrin significantly increased the expression of alpha-smooth muscle actin, but caused a decrease in proliferation. Transferrin induced a significant increase in procollagen alpha1(I) mRNA expression. In conclusion, this study has demonstrated for the first time a specific, high affinity receptor for rat transferrin on activated hepatic stellate cells, which via interaction with transferrin regulates stellate cell activation. This suggests that transferrin may be an important factor in the activation of hepatic stellate cells in conditions of iron overload.

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.

Obesity is associated with worse peritoneal dialysis outcomes in the Australia and New Zealand patient populations

Although obesity is associated with increased risks of morbidity and death in the general population, a number of studies of patients undergoing hemodialysis have demonstrated that increasing body mass index (BMI) is correlated with decreased mortality risk. Whether this association holds true among patients treated with peritoneal dialysis (PD) has been less well studied. The aim of this investigation was to examine the association between BMI and outcomes among new PD patients in a large cohort, with long-term follow-up monitoring. Using data from the Australia and New Zealand Dialysis and Transplant Registry, an analysis of all new adult patients (n = 9679) who underwent an episode of PD treatment in Australia or New Zealand between April 1, 1991, and March 31, 2002, was performed. Patients were classified as obese (BMI of greater than or equal to30 kg/m(2)), overweight (BMI of 25.0 to 29.9 kg/m(2)), normal weight (BMI of 20 to 24.9 kg/m(2)), or underweight (BMI of

Nitrifying microbial community analysis of nitrite accumulating biofilm reactor by fluorescence in situ hybridization

Biological nitrogen removal via nitrite pathway in wastewater treatment is very important especially in the cost of aeration and as an electron donor for denitrification. Wastewater nitrification and nitrite accumulations were carried out in a biofilm reactor. The biofilm reactor showed almost complete nitrification and most of the oxidized ammonium was present as nitrite at the ammonium load of 1.2 kg N/m3/d. Nitrite accumulation was achieved by the selective inhibition of nitrite oxidizers by free ammonia and oxygen limitation. Nitrite oxidation activity was recovered as soon as the inhibition factor was removed. Fluorescence in situ hybridization studies of the nitrite accumulating biofilm system have shown that genus Nitrosomonas which is specifically hybridized with probe NSM 156 was the dominant nitrifying bacteria while Nitrospira was less abundant than those of normal nitrification systems. Further FISH analysis showed that the combinations of Nitrosomonas and Nitrospira cells were identified as important populations of nitrifying bacteria in an autotrophic nitrifying biofilm system.

Assessing forest fire as a potential PCDD/F source in Queensland, Australia

Forest fires are suggested as a potential and significant source of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs), even though no studies to date provide sufficient evidence to confirm forest fires as a source of PCDD/Fs. Recent investigations in Gueensland, Australia have identified a widespread contamination of PCDDs (in particular OND) in soils and sediments in the coastal region from an unknown source of PCDD/Fs. Queensland is predominately rural; it has few known anthropogenic sources of PCDD/Fs, whereas forest fires are a frequent occurrence. This study was conducted to assess forest fires as a potential source of the unknown PCDD/F contamination in Queensland. A combustion experiment was designed to assess the overall mass of PCDD/Fs before and after a simulated forest fire. The results from this study did not identify an increase in Sigma-PCDD/Fs or OCDD after the combustion process. However, specific non-2,3,7,8 substituted lower chlorinated PCDD/Fs were elevated after the combustion process, suggesting formation from a precursor. The results from this study indicate that forest fires are unlikely to be the source of the unknown PCDD contamination in Gueensland, rather they are a key mechanism for the redistribution of PCDD/Fs from existing sources and precursors.

Effect of lifter design on drying performance in rotary dryers

Lifter use in dryers improves mass transfer by increasing the amount of surface area available for transfer and also by increasing the velocity of gas over the particle surface. An even cross-sectional distribution of particles in a dryer improves the efficiency of operation by ensuring that evaporation from falling particles is taking place for the maximum fraction of the rotation period of the drier. Studies on lifter design to improve the cross-sectional particle distribution were performed on angled lifters. A single lifter was used and the mass-transfer rate examined as a function of angular lifter displacement. Analysis of the mass transfer characteristics of single lifters allowed performance comparisons and recommendations for lifter design.

Reliability of moderate-intensity and vigorous physical activity stage of change measures for young adults

Background. The purpose of this study was to examine the reliability of stage of change (SOC) measures for moderate-intensity and vigorous physical activity in two separate samples of young adults. Staging measures have focused on vigorous exercise, but current public health guidelines emphasize moderate-intensity activity. Method. For college students in the USA (n = 105) and in Australia (n = 123), SOC was assessed separately on two occasions for moderate-intensity activity and for vigorous activity. Test-retest repeatability was determined, using Cohen's kappa coefficient. Results. In both samples, the reliability scores for the moderate-intensity physical activity staging measure were lower than the scores for the vigorous exercise staging measure. Weighted kappa values for the moderate-intensity staging measure were in the fair to good range for both studies (0.50 and 0.45); for the vigorous staging measure kappa values were excellent and fair to good (0.76 and 0.72). Conclusions. There is a need to standardize and improve methods for staging moderate-intensity activity, given that such measures are used in public health interventions targeting HEPA (health-enhancing physical activity). (C) 2003 American Health Foundation and Elsevier Science (USA). All rights reserved.

An Australian PR state?

In their 1994 study Taxation and Representation, Deacon and Golding point to the extensive use of press and public relations professionals by governments to promote policy, and to outmanouvre their opponents. With the UK specifically in mind, they warn: 'we cannot ignore the massive expansion of the public relations state.' (p.6). What distinguishes their approach from the more usual preoccupation with the use of 'spin' to 'package' political leaders is a focus on the institutionalisation of public relations within government. In this paper, I explore the utililty of the concept, and consider what the broad features of an Australian 'PR State' might be.

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.