IL-18 enhances collagen-induced arthritis by recruiting neutrophils via TNF-alpha and leukotriene B4.

IL-18 expression and functional activity have been associated with a range of autoimmune diseases. However, the precise mechanism by which IL-18 induces such pathology remains unclear. In this study we provide direct evidence that IL-18 activates neutrophils via TNF-alpha induction, which drives the production of leukotriene B(4) (LTB(4)), which in turn leads to neutrophil accumulation and subsequent local inflammation.

Developing conceptual frameworks for the recovery of aquatic biota from acidification.

Surface water acidity is decreasing in large areas of Europe and North America in response to reductions in atmospheric S deposition, but the ecological responses to these water-quality improvements are uncertain. Biota are recovering in some lakes and rivers, as water quality improves, but they are not yet recovering in others. To make sense of these different responses, and to foster effective management of the acid rain problem, we need to understand 2 things: i) the sequence of ecological steps needed for biotic communities to recover; and ii) where and how to intervene in this process should recovery stall.

Regulation of Fyn through translocation of activated Lck into lipid rafts.

Whether or how the activation of Lck and Fyn during T cell receptor (TCR) signaling is coordinated, and their delivery of function integrated, is unknown. Here we show that lipid rafts function to segregate Lck and Fyn in T cells before activation. Coaggregation of TCR and CD4 leads to Lck activation within seconds outside lipid rafts, followed by its translocation into lipid rafts and the activation of colocalized Fyn.

Ste11p, a high-mobility-group box DNA-binding protein, undergoes pheromone- and nutrient-regulated nuclear-cytoplasmic shuttling.

The high-mobility-group (HMG) box is a conserved DNA-binding domain found in a family of transcription factors that regulate growth and development. One family member, Ste11p, directs sexual differentiation of Schizosaccharomyces pombe by binding specific DNA sequences upstream of genes required for mating and meiosis. Here, we show that Ste11p is a shuttling protein.

Inactivation of Ran1/Pat1 kinase bypasses the requirement for high-level expression of mei2 during fission yeast meiosis.

Ran1/Pat1 kinase and cAMP-dependent protein kinase (PKA) regulate sexual differentiation in Schizosaccharomyces pombe. A reduction in the activity of both enzymes is a prerequisite for meiosis. Together, PKA and Pat1 control the level of expression of the Mei2 RNA-binding protein.

Glioma apoptosis induced by macrophages involves both death receptor-dependent and independent pathways.

Apoptosis of glioma may represent a promising intervention for tumor treatment. Macrophages are able to induce apoptosis in a number of tumor cells, including glioma. It is known that apoptosis of cells is executed on either a death receptor-dependent or independent pathway.

Evaluation of proximal contacts of posterior composite restorations with 4 placement techniques.

Background: Contrary to the situation for amalgam restorations, obtaining acceptable proximal contacts with posterior composite restorations can be difficult. Proximal contacts that are less than ideal may permit food impaction and subsequent caries formation and periodontal problems.

Purpose: The aim of this study was to assess the quality of proximal contacts of posterior composite restorations placed with 4 restorative techniques.

Effects of sphingosine-1-phosphate and lysophosphatidic acid on human osteoblastic cells.

The effects of the lysophospholipids, sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) were studied in human primary osteoblastic cells and the human osteosarcomal cell lines, G292 and MG-63. The studies focused on the role of the Gi protein in the regulation of S1P and LPA-induced proliferation, the effects of the phospholipids on alkaline phosphatase, an early marker of osteoblastic cell proliferation, and the presence of edg receptors. Proliferation was assessed by 3H-thymidine incorporation.

A novel anti-inflammatory role for simvastatin in inflammatory arthritis.

3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) exert favorable effects on lipoprotein metabolism, but may also possess anti-inflammatory properties. Therefore, we explored the activities of simvastatin, a lipophilic statin, in a Th1-driven model of murine inflammatory arthritis. We report in this study that simvastatin markedly inhibited not only developing but also clinically evident collagen-induced arthritis in doses that were unable to significantly alter cholesterol concentrations in vivo.

An ounce of prevention or a pound of cure: bioeconomic risk analysis of invasive species.

Numbers of non-indigenous species--species introduced from elsewhere - are increasing rapidly worldwide, causing both environmental and economic damage. Rigorous quantitative risk-analysis frameworks, however, for invasive species are lacking. We need to evaluate the risks posed by invasive species and quantify the relative merits of different management strategies (e.

A novel dendritic cell-induced model of erosive inflammatory arthritis: distinct roles for dendritic cells in T cell activation and induction of local inflammation.

Transferring collagen-pulsed, bone marrow-derived dendritic cells (DCs) into congenic DBA/1 recipient mice produced arthritis in joints adjacent to the site of DC transfer and could be inhibited by treatment with TNF antagonists. Disease was Ag specific, as transfer of control, unpulsed DCs, or DCs pulsed with OVA did not produce arthritis. In contrast to other experimental arthritis models, DC-induced arthritis localized to the site of injection and did not spontaneously generalize to uninvolved joints, despite the demonstration of circulating collagen-reactive T cells.

Induction of apoptosis in glioma cells by molecules released from activated macrophages.

Macrophages play an important role in the regulation of malignant tumors. Although glioma contains abundance of macrophages, their role in apoptosis of glioma is not known. We stimulated macrophages with lipopolysaccharide and culture supernatants of activated macrophages were collected to treat glioma cells.

Activation of Kupffer cells inhibits tumor growth in a murine model system.

Kupffer cells, a liver organ-specific macrophage, play an important role in preventing the development of malignant tumors. The mechanism responsible for their tumoricidal activities is not completely known. In our study, we established in vivo models involving a rat malignant cell line, rat Kupffer cells and tumor implantation in nude mice.

Novel pathways that regulate tumor necrosis factor-alpha production in rheumatoid arthritis.

Clinical intervention studies have clearly shown the benefit in suppressing tumor necrosis factor-alpha (TNF-alpha) rheumatoid arthritis (RA). In consequence, considerable interest has arisen in those pathways that in turn regulate TNF-alpha production, because they may offer further possible therapeutic targets. Several candidate pathways are currently being investigated.

Galanin in human pituitary adenomas: frequency and clinical significance.

Objectives: Galanin (GAL) is a neuropeptide widely expressed in the central and peripheral nervous system and in neuroendocrine tissue, including the adenohypophysis where, in humans, it is expressed in corticotrophs and in ACTH-producing adenomas. Previous analyses of human tissue have used antiserum against porcine GAL for detection of GAL immunoreactivity (GAL-IR) and no pathophysiological correlates have been reported. Given significant differences between the sequence of porcine and human GAL peptides, the aim of this study was to use antiserum raised against synthetic human GAL to investigate GAL-IR in non tumorous pituitaries and in pituitary adenomas, and to correlate GAL-IR with the clinical and hormonal characteristics of patients with Cushing's disease.

Enhanced Th1 response to Staphylococcus aureus infection in human lactoferrin-transgenic mice.

Lactoferrin (Lf) is an iron-binding protein of external secretions and neutrophil secondary granules with antimicrobial and immunomodulatory activities. To further define these properties of Lf, we have investigated the response to Staphylococcus aureus infection in transgenic mice carrying a functional human Lf gene. The transgenic mice cleared bacteria significantly better than congenic littermates, associated with a trend to reduced incidence of arthritis, septicemia, and mortality.

Evidence of an association between human papillomavirus and impaired chemotherapy-induced apoptosis in cervical cancer cells.

Objectives: The aim of this study was to determine cervical cancer cell sensitivity to chemotherapy-induced apoptosis based on human papillomavirus (HPV) status.

Methods: CaSki (HPV-positive) and C33A (HPV-negative) cells were treated with camptothecin or cisplatin. Cellular viability was determined by trypan blue exclusion.

Relaxation training as complementary therapy for mild hypertension control and the implications of evidence-based medicine.

Relaxation therapy for the treatment of hypertension presented a number of challenges, in terms of conducting and using research as well as gaining the wider acceptance of this complementary therapy in common practice in Hong Kong. Two issues were central to the current implementation of complementary therapies: the evidence-based practice movement and the management of risk during the implementation of new therapies. A major concern was how to maximize the chance of inclusion of research on complementary therapies in evidence-based practice systematic reviews.

Induction of Fas and Fas ligand expression on malignant glioma cells by Kupffer cells, a potential pathway of antiliver metastases.

Kupffer cells play an important role in controlling the growth and development of liver metastases. However, the pathway of Kupffer cells against tumor metastases is not clear. In the present study, we set up an experimental model to investigate the mechanisms on how Kupffer cells kill tumor cells which metastasize to the liver.

Decreased expression of Bid in human hepatocellular carcinoma is related to hepatitis B virus X protein.

As a mitochondrial membrane death ligand, Bid oligomerises Bak to release cytochrome C and its deficiency renders hepatocytes resistant to apoptosis induced by Fas. The Bid level in hepatocellular carcinoma (HCC) is unknown. In this report, we examined the expression of Bid protein and mRNA in HCC cancerous tissues and their corresponding non-cancerous ones.

A role for IL-18 in neutrophil activation.

IL-18 expression and functional activity has been identified in several autoimmune and infectious diseases. To clarify the potential role of IL-18 during early innate immune responses, we have explored the capacity of IL-18 to activate neutrophils. Human peripheral blood-derived neutrophils constitutively expressed IL-18R (alpha and beta) commensurate with the capacity to rapidly respond to IL-18.

The Sushi domain of soluble IL-15 receptor alpha is essential for binding IL-15 and inhibiting inflammatory and allogenic responses in vitro and in vivo.

IL-15 is a pleiotropic cytokine that plays important roles in both innate and adaptive immunity. It is associated with a range of immunopathology, including rheumatoid arthritis and allograft rejection. IL-15 functions through the trimeric IL-15R complex, which consists of a high affinity binding alpha-chain and the common IL-2R beta- and gamma-chains.

A novel pathway regulating lipopolysaccharide-induced shock by ST2/T1 via inhibition of Toll-like receptor 4 expression.

ST2/ST2L, a member of the IL-1R gene family, is expressed by fibroblasts, mast cells, and Th2, but not Th1, cells. It exists in both membrane-bound (ST2L) and soluble forms (ST2). Although ST2L has immunoregulatory properties, its ligand, cellular targets, and mode of action remain unclear.