Notch signalling and voltage-gated Na+ channel activity in human prostate cancer cells: independent modulation of in vitro motility.

This study tested the possible functional relationship of two signalling mechanisms shown previously to be involved in human prostate cancer (PCa), Notch and voltage-gated sodium channel. Notch1 and Notch2 were differentially expressed in PCa cell lines of varying metastatic potential (LNCaP, PC-3, PC-3M) in comparison to a normal prostate cell line (PNT2), whereas Notch3 and Notch4 were not expressed. The Notch ligand Jagged1, but not Jagged2, was increased in all cell lines, whereas the Notch downstream target Deltex was not expressed. In comparison to the LNCaP cell line, Hes1, another downstream target, showed elevated expression in the metastatic PC-3 and PC-3M cells and promoted lateral motility. In contrast, the Notch ligand Delta-like1 (Dll1) levels were higher in LNCaP compared with PC-3 and PC-3M cells. Importantly, decreasing Dll1 expression increased the lateral motility of PC-3 cells, whereas blocking voltage-gated Na(+) channel activity with tetrodotoxin decreased motility. However, the effect of Dll1 was independent of Notch signalling through Hes1 and voltage-gated Na(+) channel expression/activity.

Natural killer cells in the synovial fluid of rheumatoid arthritis patients exhibit a CD56bright,CD94bright,CD158negative phenotype.

BACKGROUND: Natural killer (NK) cells play an important role in several animal models of autoimmunity by modulating T-cell responses, but it is unclear whether human NK cells have similar functions. METHODS: We characterized the phenotype of NK cells in synovial fluid (SF) and peripheral blood (PB) of patients with rheumatoid arthritis (RA) and in healthy control subjects using flow cytometry and quantitative PCR. RESULTS: The proportions of NK cells in PB and SF of RA patients were not significantly different from those in healthy PB. However, the SF NK cell phenotype was strikingly different, with increased CD94 and CD56 densities and greatly reduced proportions of cells expressing CD158a/b. These cells also had reduced mRNAs coding for CD158a/b and low perforin levels compared with RA PB and healthy PB NK cells. CONCLUSIONS: We identified a novel phenotype of SF NK cells that is of potential significance in RA. Experiments are now under way to determine the function of these SF NK cells and their potential role in RA.

Assessment of latex allergy in a healthcare population: are the available tests valid?

BACKGROUND: Latex allergy can cause serious, preventable work-related health problems in healthcare workers who are a high risk group for this form of allergy. Type I hypersensitivity can produce life-threatening systemic effects, and involves an allergen-specific immunoglobulin (IgE) response to proteins found in latex. The estimated prevalence of latex 'allergy' in healthcare workers varies widely (2.8% - 18%), and studies do not always distinguish between those who are positive in an assay for latex-specific IgE and those with clinical allergy. OBJECTIVE: To assess the performance of four in-vitro methods and three skin testing methods for detecting latex-specific IgE in a group of UK healthcare workers. Test results were compared with reported clinical symptoms defined by questionnaire. METHODS: Skin prick testing was carried out on volunteers using three reagents: (a) stallergenes commercial latex extract (Cedex, France); (b) an in-house latex glove extract; and (c) a fresh glove piece. Specific IgE levels were determined using Pharmacia AutocapTM (Uppsala, Sweden), Pharmacia UnicapTM (Uppsala, Sweden), DPC Immulite(R) (Los Angeles, USA) and Hycor HytecTM (Irvine, California, USA) methods. Each volunteer completed a questionnaire detailing latex exposure and allergic history. RESULTS: In vitro methods for detecting specific IgE to natural rubber latex were positive in 3.6%, to 43.6% of the same population. Skin prick tests positivity varied between 2. 9% and 14.3% with different extracts. From the subjects tested 9.1% reported symptoms which could be consistent with type I allergy, although none had been given a pre-existing diagnosis of latex allergy, and 43.6% of volunteers reported symptoms consistent with type IV hypersensitivity or irritant dermatitis. Contingency tables and chi-squared analysis revealed no correlation between most methods. No correlation was shown between symptoms consistent with type I allergy and any in vitro or skin testing method for latex-specific IgE. CONCLUSIONS: A wide variation between testing procedures was found, and no method could be correlated with reported symptoms of type I allergy. At least one in vitro specific IgE assay produced a high percentage of positive results at variance with the clinical symptoms in volunteers. A clinical history is essential in establishing type I hypersensitivity to latex and test results should not be used in isolation. The incidence of clinical sensitization may be seriously over-estimated if only laboratory parameters are used.