Ferritin functions as a proinflammatory cytokine via iron-independent protein kinase C zeta/nuclear factor kappaB-regulated signaling in rat hepatic stellate cells.

Unlabelled: Circulating ferritin levels reflect body iron stores and are elevated with inflammation in chronic liver injury. H-ferritin exhibits a number of extrahepatic immunomodulatory properties, although its role in hepatic inflammation and fibrogenesis is unknown. Hepatic stellate cells respond to liver injury through production of proinflammatory mediators that drive fibrogenesis.

Interacting signals in the control of hepcidin expression.

The amount of iron in the plasma is determined by the regulated release of iron from most body cells, but macrophages, intestinal enterocytes and hepatocytes play a particularly important role in this process. This cellular iron efflux is modulated by the liver-derived peptide hepcidin, and this peptide is now regarded as the central regulator of body iron homeostasis. Hepcidin expression is influenced by systemic stimuli such as iron stores, the rate of erythropoiesis, inflammation, hypoxia and oxidative stress.

A systematic approach to analysing gene-gene interactions: polymorphisms at the microsomal epoxide hydrolase EPHX and glutathione S-transferase GSTM1, GSTT1, and GSTP1 loci and breast cancer risk.

Objective: We undertook a case-control study in an Australian Caucasian population-based sample of 1,246 cases and 664 controls to assess the roles of detoxification gene polymorphisms EPHX T>C Tyr(113)His, GSTT1 deletion, GSTM1 deletion, and GSTP1 A>G Ile(105)Val on risk of breast cancer.

Methods: We systematically addressed the main effects and possible gene-gene interactions using unconditional logistic regression to estimate odds ratios (OR) adjusted for potential confounders and using standard model building approaches based on likelihood theory.

Results: There was a decreased risk associated with the EPHX CC genotype [OR, 0.

Identification of a diagnostic antibody-binding region on the immunogenic protein EpC1 from Echinococcus granulosus and its application in population screening for cystic echinococcosis.

An Echinococcus granulosus cDNA sequence coding for EpC1, a proven serodiagnostic marker for cystic echinococcosis (CE, hydatid disease), has high amino acid sequence identity to a paralogue from Taenia solium, the cause of neurocysticercosis (NCC). To determine diagnostic antibody-binding regions on EpC1 recognized specifically by CE sera, 10 truncated regions (P1-10) of the immunogenic protein were expressed in Escherichia coli and subjected to immunoblotting. One peptide, designated peptide 5 [P5, fused with glutathione-S-transferase (GST)] was positively recognized by sera from mice experimentally infected with oncospheres of E.

Sublethal effects of mosquito larvicides on swimming performance of larvivorous fish Melanotaenia duboulayi (Atheriniformes: Melanotaeniidae).

Laboratory studies were conducted to determine the sublethal effects of exposure to selected larvicides on the critical swimming speed (Ucrit) of crimson-spotted rainbowfish, Melanotaenia duboulayi (Castlenau). This native fish is common throughout southeastern Queensland, and it is increasingly being distributed as a biological control agent of mosquitoes. The selected larvicides included, two organophosphate (OP) compounds (temephos and pirimiphos-methyl), two microbial larvicides (Bacillus thuringiensis spp.

Evaluation of Melanotaenia duboulayi (Atheriniformes: Melanotaeniidae), Hypseleotris galli (Perciformes: Eleotridae), and larvicide VectoLex WG (Bacillus sphaericus) for integrated control of Culex annulirostris.

Australian freshwater fish species Melanotaenia duboulayi and Hypseleotris galii were selected for a small plot field evaluation of an integrated pest management strategy using native fish and VectoLex WG (Bacillus sphaericus) for the control of Culex annulirostris Skuse, the principal freshwater vector of arbovirus Ross River virus in Australia. When tested alone, the level of control afforded by M. duboulayi and H.

Laboratory evaluation of the effect of alternative prey and vegetation on predation of Culex annulirostris immatures by Australian native fish species.

The impact of alternative prey and simulated vegetation on Culex annulirostris Skuse predation efficacy by Australian smelt, Retropinna semoni (Retropinnidae); crimson-spotted rainbowfish, Melanotaenia duboulayi (Melanotaeniidae); empire gudgeon, Hypseleotris compressa (Eleotridae); estuary perchlet, Ambassis marianus (Ambassidae); firetail gudgeon, Hypseleotris galii (Eleotridae); fly-specked hardyhead, Craterocephalus stercusmuscarum (Atherinidae); and Pacific blue-eye, Pseudomugil signifer (Atherinidae), was evaluated in Queensland, Australia. The presence of chironomid midge larvae and tusked frog, Adelotus brevis (Leptodactylidae), tadpoles did not have a significant negative impact on the predation rates of Cx. annulirostris by these 7 fish species.

Corticosteroid therapy in an alphaviral arthritis.

Background: : Corticosteroid use during acute viral arthritis is considered to be contraindicated as a result of the risk of immunosuppression causing enhanced infection and disease exacerbation.

Objectives: : The objective of this study was to analyze the effect of oral corticosteroid therapy on symptoms of the viral arthritic disease, Ross River virus disease (RRVD).

Methods: : Patients with RRVD were enrolled in 2 prospective longitudinal studies.

Familial aggregation of human infection with Schistosoma japonicum in the Poyang Lake region, China.

Despite the success of extensive control measures that have been implemented in China for over 50 years, the number of individuals infected with Schistosoma japonicum remains high in the existing endemic areas. A variance components analysis was undertaken to estimate the heritable and environmental components that contribute to S. japonicum infection in the Poyang Lake region of Jiangxi Province, PR China.

Unequal treatment access and malaria risk in a community-based intervention program in the Philippines.

This study assesses the influence of several malaria risk factors and volunteer health worker (VHW) accessibility on parasite prevalence and treatment-seeking in a remote area of Mindanao, the Philippines. An anti-malaria program in the area seeks to devolve malaria diagnosis and treatment to the VHWs. Firstly, the relationship between malaria and demographic factors, bednet use, and access to treatment was investigated.

In vitro and in silico analysis of signal peptides from the human blood fluke, Schistosoma mansoni.

Proteins secreted by and anchored on the surfaces of parasites are in intimate contact with host tissues. The transcriptome of infective cercariae of the blood fluke, Schistosoma mansoni, was screened using signal sequence trap to isolate cDNAs encoding predicted proteins with an N-terminal signal peptide. Twenty cDNA fragments were identified, most of which contained predicted signal peptides or transmembrane regions, including a novel putative seven-transmembrane receptor and a membrane-associated mitogen-activated protein kinase.

Environmental predictors of Ross River virus disease outbreaks in Queensland, Australia.

Ross River virus (RRV) disease is the most common mosquito-borne disease in Australia, with the majority of cases reported from Queensland. In this study we investigate the relationship between local RRV disease outbreaks and standardized rainfall and temperature data in Queensland. No one set of variables could be found to accurately predict RRV disease outbreaks across all of Queensland, although good predictive models could be developed for smaller regions.

RAD52 Y415X truncation polymorphism and epithelial ovarian cancer risk in Australian women.

The RAD52 gene is involved in the homologous recombination repair pathway and is a plausible candidate ovarian cancer predisposition gene. We undertook a case-control comparison of 508 epithelial ovarian cancer cases (91 low malignant potential and 417 invasive) and 298 healthy controls to assess the RAD52 Y415X polymorphism as a risk factor for epithelial ovarian cancer in Australian women. Heterozygote frequencies of 2.

Differences in climatic factors between Ross River virus disease outbreak and nonoutbreak years.

Ross River virus is a common mosquito-borne arbovirus responsible for outbreaks of polyarthritic disease throughout Australia. To better understand climatic factors preceding outbreaks, we compared seasonal and monthly rainfall and temperature trends in outbreak and nonoutbreak years at four epidemic-prone locations. Our analyses showed that rainfall in outbreak years tended to be above average and higher than rainfall in nonoutbreak years.

Codon usage and bias in mitochondrial genomes of parasitic platyhelminthes.

Sequences of the complete protein-coding portions of the mitochondrial (mt) genome were analysed for 6 species of cestodes (including hydatid tapeworms and the pork tapeworm) and 5 species of trematodes (blood flukes and liver- and lung-flukes). A near-complete sequence was also available for an additional trematode (the blood fluke Schistosoma malayensis). All of these parasites belong to a large flatworm taxon named the Neodermata.

Increased hepcidin expression and hypoferraemia associated with an acute phase response are not affected by inactivation of HFE.

The effect of HFE inactivation on iron homeostasis during an acute phase response was investigated in mice. HFE knockout, beta2-microglobulin knockout and C57BL/6J mice were injected with Freund's Complete Adjuvant to induce an acute phase response and hepatic hepcidin expression and serum transferrin saturation was determined 16 h later. Hepcidin mRNA increased in all strains in response to an acute phase stimulus when compared with untreated control animals.

Schistosome transcriptome analysis at the cutting edge.

We live in the era of post-genomics, a term that was, until recently, inappropriate when considering the blood flukes of humans because of the relative lack of knowledge of the schistosome genome. The position has, however, changed dramatically following the recent publication of two landmark papers on transcriptome analysis of Schistosoma japonicum and Schistosoma mansoni. In a quantum leap, both studies report on the identification of many novel genes and genes not previously known from schistosomes.

ISCOM based vaccines for cancer immunotherapy.

Immunostimulating complex (ISCOM) vaccines are particulate antigen delivery vehicles composed of saponin, cholesterol, phospholipid and immunogen. Here we illustrate that ISCOM-based vaccines represent an attractive modality for the development of anti-cancer vaccines. Using murine models and a model cancer antigen, ISCOM vaccines were shown to induce potent CD8 T cell responses, to mediate protection in three different tumor models, to promote Th1-biased immunity, and to induce CD8 T cell responses in the absence of CD4+ T cell help.

Ross River virus disease in Australia, 1886-1998, with analysis of risk factors associated with outbreaks.

Ross River virus (RR) is a mosquito-borne arbovirus responsible for outbreaks of polyarthritic disease throughout Australia. To better understand human and environmental factors driving such events, 57 historical reports on RR outbreaks between 1896 and 1998 were examined collectively. The magnitude, regularity, seasonality, and locality of outbreaks were found to be wide ranging; however, analysis of climatic and tidal data highlighted that environmental conditions act differently in tropical, arid, and temperate regions.

Molecular epidemiology of cystic echinococcosis.

Echinococcus granulosus exhibits substantial genetic diversity that has important implications for the design and development of vaccines, diagnostic reagents and drugs effective against this parasite. DNA approaches that have been used for accurate identification of these genetic variants are presented here as is a description of their application in molecular epidemiological surveys of cystic echinococcosis in different geographical settings and host assemblages. The recent publication of the complete sequences of the mitochondrial (mt) genomes of the horse and sheep strains of E.

Genomics of parasitic flatworms.

Although we live in what is often touted as the 'post-genomic era', this term is hardly appropriate when we consider the paucity of knowledge of the genomic biology of parasitic flatworms. The situation is, however, changing-at least for two species of Schistosoma. Recent transcriptome analysis of Schistosoma mansoni and of Schistosoma japonicum has identified novel genes and genes not previously reported for schistosomes, as well as the identification of the molecular mechanisms for host-dependent maturation, immune evasion, development, signalling and sexual dimorphism.

Functional expression and characterization of Echinococcus granulosus thioredoxin peroxidase suggests a role in protection against oxidative damage.

A full-length cDNA sequence coding for Echinococcus granulosus thioredoxin peroxidase (EgTPx) was isolated from a sheep strain protoscolex cDNA library by immunoscreening using a pool of sera from mice infected with oncospheres. EgTPx expressed as a fusion protein with glutathione S-transferase (GST) exhibited significant thiol-dependent peroxidase activity that protected plasmid DNA from damage by metal-catalyzed oxidation (MCO) in vitro. Furthermore, the suggested antioxidant role for EgTPx was reinforced in an in vivo assay, whereby its expression in BL21 bacterial cells markedly increased the tolerance and survival of the cells to high concentrations of H2O2 compared with controls.

A novel recombinant antigen for immunodiagnosis of human cystic echinococcosis.

A pool of serum samples from mice infected with oncospheres (eggs) of Echinococcus granulosus was used to screen a cDNA library constructed with RNA extracted from protoscolex larvae from sheep hydatid cysts. One immunoreactive clone, designated EpC1, was shown to encode a protein of 76 residues. The complementary DNA (cDNA) fragment was subcloned into an expression vector, pET-41b(+), and the resulting recombinant EpC1 glutathione S-transferase (GST) fusion protein (rEpC1-GST) was expressed in Escherichia coli and was affinity purified against the GST tag.

Echinococcosis.

Echinococcosis is a near-cosmopolitan zoonosis caused by adult or larval stages of cestodes belonging to the genus Echinococcus (family Taeniidae). The two major species of medical and public health importance are Echinococcus granulosus and Echinococcus multilocularis, which cause cystic echinococcosis and alveolar echinococcosis, respectively. Both are serious and severe diseases, the latter especially so, with high fatality rates and poor prognosis if managed incorrectly.