ANTIBODIES DIRECTED TO INDIVIDUAL HISTONES IN JUVENILE CHRONIC ARTHRITIS. ASSOCIATION WITH UVEITIS

The trials for identification of the specific target antigen for antinuclear antibodies (ANA) in juvenile chronic arthritis (JCA) revealed that a significant number of patients produce antibodies directed to individual histories and histone peptides. Fifty JCA patients, 58 healthy children and 58 children with autoimmune and rheumatologic disorders were studied for a presence of IgG- and IgM-antibodies against histone 1, histone 2 and histone 3 measured by ELISA. The levels of IgGand IgM-antibodies directed to histone 1, 2 and 3 were elevated in JCA as compared to the healthy controls. IgG-antibodies to histone 2 and IgM-antibodies to histone 3 also were elevated in comparison with the disease controls. IgG- and IgM-antibodies against histone 1 were found to be positive in 30 % and 26 % of JCA patients, respectively, in significant association with ANA (p = 0,038 and p = 0,03, respectively) and uveitis (p = 0,02 and p = 0,016, respectively). The same prevalence of IgG- and IgM-antibodies to histone 2 was established but only the IgG-isotype showed significant association with uveitis (p = 0,018). Anti-histone 3 IgG- and IgM-antibodies were found in 34 % and 27 % of JCA patients, respectively. IgM-antibodies to histone 3 were proved to be significantly associated with uveitis (p - 0,009). It was concluded that antibodies to histone 1, histone 2, and histone 3 represented a common serological feature of JCA. Their presence was related to the manifestation of chronic anterior uveitis, associated with JCA

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CpG-island methylation of the ER promoter in colorectal cancer: analysis of micrometastases in lymph nodes from UICC stage I and II patients

Patients with UICC stage II colorectal cancer (CRC) have a risk of approximately 20% to develop disease recurrence after tumour resection. The presence and significance of micrometastases for locoregional recurrence in these patients lacking histopathological lymph node involvement on routine stained HE sections is undefined. Oestrogen receptor (ER) promoter methylation has earlier been identified in CRC. Therefore, we evaluated the methylation status of the ER promoter in lymph nodes from 49 patients with CRC UICC stage I and II as a molecular marker of micrometastases and predictor of local recurrence. DNA from 574 paraffin-embedded lymph nodes was isolated and treated with bisulphite. For the detection of methylated ER promoter sequences, quantitative real-time methylation-specific PCR was used. Of the 49 patients tested, 15 (31%) had ER methylation-positive lymph nodes. Thirteen of those (86%) remained disease free and two (14%) developed local recurrence. In the resected lymph nodes of 34 of the 49 patients (69%), no ER promoter methylation could be detected and none of these patients experienced a local relapse. The methylation status of the ER promoter in lymph nodes of UICC stage I and II CRC patients may be a useful marker for the identification of patients at a high risk for local recurrence

Expression of gibberellin 20-oxidase1 (AtGA20ox1) in Arabidopsis seedlings with altered auxin status is regulated at multiple levels

Bioactive gibberellins (GAs) affect many biological processes including germination, stem growth, transition to flowering, and fruit development. The location, timing, and level of bioactive GA are finely tuned to ensure that optimal growth and development occur. The balance between GA biosynthesis and deactivation is controlled by external factors such as light and by internal factors that include auxin. The role of auxin transport inhibitors (ATIs) and auxins on GA homeostasis in intact light-grown Arabidopsis thaliana (L.) Heynh. seedlings was investigated. Two ATIs, 1-N-naphthylthalamic acid (NPA) and 1-naphthoxyacetic acid (NOA) caused elevated expression of the GA biosynthetic enzyme AtGA20-oxidase1 (AtGA20ox1) in shoot but not in root tissues, and only at certain developmental stages. It was investigated whether enhanced AtGA20ox1 gene expression was a consequence of altered flow through the GA biosynthetic pathway, or was due to impaired GA signalling that can lead to enhanced AtGA20ox1 expression and accumulation of a DELLA protein, Repressor of ga1-3 (RGA). Both ATIs promoted accumulation of GFP-fused RGA in shoots and roots, and this increase was counteracted by the application of GA4. These results suggest that in ATI-treated seedlings the impediment to DELLA protein degradation may be a deficiency of bioactive GA at sites of GA response. It is proposed that the four different levels of AtGA20ox1 regulation observed here are imposed in a strict hierarchy: spatial (organ-, tissue-, cell-specific) > developmental > metabolic > auxin regulation. Thus results show that, in intact auxin- and auxin transport inhibitor-treated light-grown Arabidopsis seedlings, three other levels of regulation supersede the effects of auxin on AtGA20ox1