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Interneurons are critical for shaping neuronal circuit activity in many parts of the central nervous system. To study interneuron function in the basal ganglia, we tested and characterized an NK-1 receptor-based method for targeted ablation of specific classes of interneuron in the striatum. Our findings demonstrate that the neurotoxin SP-PE35, a substance P-Pseudomonas exotoxin conjugate, selectively targets striatal cholinergic and nitric oxide synthase/somatostatinergic interneurons when injected locally into the striatum. The effects of this selective cell targeting encompassed alterations in both behavioral and neural responses to dopaminergic stimulation, including altered patterns of early-gene response in striosomes and matrix. We conclude that NK-1-bearing local circuit neurons of the striatum regulate the differential responses of striatal projection neurons to dopamine-mediated signaling.

Human and animal data have demonstrated H.pylori induced platelet aggregation in gastric vasculature. Formation of platelet aggregates may contribute to the pathogenesis of H.pylori associated gastric injury and may also [...]

Although COX-1 is often referred to as a constitutively expressed gene, we have previously described induction of COX-1 as well as COX-2 by H. pylori suggesting that COX-1 may contribute [...]

There is growing evidence that H. pylori exerts some of its effects on the stomach by actions on the gastric vasculature. We have shown upregulation of both isoforms of COX [...]

Several studies have demonstrated that H. pylori induces COX-2 in gastric mucosa and suggested that this may explain the increased risk of gastric cancer with H. pylori infection. We have [...]

Aims: COX-2 plays a crucial role in colorectal carcinogenesis and selective COX-2 inhibitors have been shown to have antineoplastic effects in vitro and in vivo. The precise mechanisms underlying these [...]

Aims: γ-Catenin (Plakoglobin) is a member of the catenin family. It functions in cell adhesion and the WNT signalling pathway. Defects in both WNT signalling and COX-2 expression play important [...]

Summary: Objective: Basic calcium phosphate (BCP) crystals have been implicated in the pathogenesis of osteoarthritis (OA), in part because of their ability to upregulate cyclooxygenase and prostaglandin E2 (PGE2) production. The aim of this work was to investigate the expression of terminal PGE2 synthases and PGE2 receptors (EP) in BCP crystal-stimulated fibroblasts. Methods: Cultured fibroblasts were stimulated with BCP crystals in vitro. mRNA expression was measured by real-time polymerase chain reaction, and protein production by western blotting. Results: Basal expression of microsomal prostaglandin E2 synthase 1 (mPGES1) in osteoarthritic synovial fibroblasts (OASF) was found to be 30-fold higher than in human foreskin fibroblasts (HFF). BCP crystals increased mPGES1 expression fourfold in HFF, but not in OASF. EP4 expression was downregulated twofold by BCP crystals in OASF, but not in HFF. Exogenous PGE2 also downregulated EP4 expression; this effect was blocked by co-administration of L-161,982, a selective EP4 antagonist. While administration of exogenous PGE2 significantly upregulated mPGES1 expression in OASF, mPGES1 expression was threefold higher in the OASF treated with BCP crystals and PGE2 as compared with OASF treated with PGE2 alone. Conclusions: The differing effects of BCP crystals on mPGES1 expression in HFF and OASF may be explained by BCP crystal-induced EP4 downregulation in OASF, likely mediated via PGE2. These data underline the complexity of the pathways regulating PGE2 synthesis and suggest the existence of a compensatory mechanism whereby mPGES1 expression can be diminished, potentially reducing the stimulus for further PGE2 production. [Copyright &y& Elsevier]

Examines the accuracy and working condition of 210 sphygmomanometers in hospital and family practice. Cause of faults in the inflation-deflation system; Percentage of leakage occurrence of the hospital and family practice sphygmomanometers; Maintenance of sphygmomanometers.

Background: Clinical studies have suggested an association between cardiovascular disease and infection with H pylori. We have described strain specific H pylori-induced platelet aggregation that involves platelet glycoprotein lb and van Willebrand factor (vWf). We exam ned the role of H pylori antibodies in this aggregation. Methods and Results: Addition of pooled immunoglobin (Ig) and fibrinogen along with H pylori strain 60190 (coated in vWf) to washed platelets led to platelet aggregation (60±4% n=3). Antibodes involved were specific to H pylori as bacteria incubated in pooled g and subsequently washed could support platelet aggregation (49±7%, n=3). To confirm this, pooled Ig was incubated with H pylori or Streptococcus sanguis. Bacteria were removed by centrifugation and the depleted g used in aggregation assays. H pylori-depleted Ig showed greatly reduced platelet aggregation to H pylori (13±9%, n=3, p<0.01) while the S sanguis-depleted Ig was not affected (54±3%, n=3, p=NS). All 20 plasma donors were tested for H pylori seropositivity using a H pylori ELISA. All 4/4 of the positive volunteers consistent y aggregated in response to H pylori while only 2/15 of the H pylori negative donors aggregated consistently (p=0.039, Fisher's Exact Test). The relative risk of H pylori positivity for aggregation was 7.5 (CI 2.0-27.3). Conclusions: H pylori-induced platelet aggregation requires binding of H pylori-specific IgG. This pro-aggregatory phenotype is not unique to H pylori and has been described with S sanguis and P gingivalis. Exposure to oral bacteria such as S sanguis can lead to infective endocarditis and in the case of P gingivalis, to enhancement of atherosclerosis in animal models. Repeated exposure to proaggregatory bacteria such as certain strains of H pylori may not cause coronary artery disease but could accelerate the progression of the disease. Local platelet effects may also contribute to the pathogenesis of H... [ABSTRACT FROM AUTHOR]