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Objectives. The aim of this study was to determine the clinical characteristics of Behcets disease (BD) associated with bone marrow failure (BMF), classified as conditions such as myelodysplastic syndrome (MDS) or aplastic anaemia (AA), in Korea. Methods. A retrospective analysis was made of 13 patients with BD associated with BMF (MDS 8 cases, AA 5 cases) and 66 patients with BD not associated with BMF. These patients all fulfilled the diagnostic criteria of the international BD study group. Results. BD patients with BMF showed significantly lower leucocyte count, haemoglobin level and platelet count when compared with patients without BMF (P P = 0.03). Intestinal lesions were more frequent in BD patients with BMF than those without BMF (61.5% vs 13.6%, P = 0.001). Cytogenetic abnormality was observed in 90.9% of BD patients with BMF. Of the cytogenetic abnormalities, trisomy 8 was most common, occurring in 70% of the patients. In four patients with refractory BD associated with BMF, successful treatment of BMF by haematopoietic stem cell transplantation resulted in clinical remission of BD. Conclusions. Our study indicates that intestinal ulceration is a characteristic finding in BD associated with BMF. It also suggests that cytogenetic aberration, especially trisomy 8, may play an important role in the pathogenesis of BD associated with BMF. [ABSTRACT FROM AUTHOR]

Objectives. Hypoxia-inducible factor-1α (HIF-1α) is a master regulator in the cellular response to hypoxic conditions, and rheumatoid synovial tissue is known to exist under hypoxic conditions. Therefore, this study was conducted to determine the contribution of HIF-1α to hypoxia-induced MMP and cytokine production in fibroblast-like synoviocytes (FLS). Methods. RA FLS were transfected with either a plasmid that expresses HIF-1α or an empty vector as a control, and then cultured under normoxia (21% O2). Also, FLS were transfected with either HIF-1α small interfering RNA (siRNA) or control siRNA, and cultured under hypoxic conditions (1% O2). Following transfection, the amounts of MMP and cytokine mRNAs and HIF-1α protein were examined using real-time RT–PCR and western blotting, respectively. Results. The expression of HIF-1α, MMP-1, MMP-3, IL-6 and IL-8 was markedly enhanced in FLS that were cultured under hypoxia. We confirmed that transient transfection of HIF-1α overexpressing vector or siRNA had occurred using western blotting, and in vitro studies conducted using FLS transfected with HIF-1α overexpression vector showed that they had significantly increased MMP-1, MMP-3 and IL-8 expression levels. Further, hypoxia-induced MMP-3 expression was significantly attenuated by knock-down of HIF-1α, whereas hypoxia-induced IL-8 or MMP-1 expression was not significantly repressed by HIF-1α siRNA. Conclusions. Hypoxia-induced MMP-3 expression is exclusively regulated by HIF-1α, and hypoxia-induced MMP-1 or IL-8 expression appears to have salvage pathways other than the HIF-1α pathway. Together, these data provide new insight regarding the mechanism by which hypoxia participates in joint inflammation and destruction in RA. [ABSTRACT FROM AUTHOR]