SUMMARYMatrix metalloproteinases (MMPs) play an important role in the progression of tumour cells and the invasion of inflammatory cells by degrading the extracellular matrix. In the MMP family, MMP-9 gelatinase is thought to contribute to the pathogenesis of inflammatory arteritis by disrupting the elastic lamina. The aim of the present study is to investigate the potential role of MMP-9 in Kawasaki disease (KD), an acute type of systemic vasculitis in children. We studied the total levels of MMP-9 (free proMMP-9 and free MMP-9) in the sera using a new assay system and the expression of MMP-9 mRNA in the leucocytes using reverse transcription-polymerase chain reaction in 18 patients with KD, 10 patients with sepsis and 10 healthy children (HC). The serum MMP-9 levels were significantly higher (P , 0´01) in the acute phase of KD than in the acute phase of sepsis and HC. In the time course of KD, the serum MMP-9 levels decreased significantly (P , 0´01) from the subacute through the convalescent phases. In the acute phase of KD, the serum MMP-9 levels showed a significantly positive correlation (P , 0´05) with the circulating leucocyte counts, especially the neutrophil counts. Furthermore, the expression of MMP-9 mRNA in the circulating leucocytes increased in the acute phase of KD and decreased from the subacute through the convalescent phases. These findings indicate that an excessive amount of MMP-9 is present in the plasma during the acute phase of KD, thus suggesting that circulating leucocytes may be a source of the MMP-9 secreted into the circulation.

Background: Distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy (DMRV)/hIBM is a sialic aciddeficient myopathy. Results: Tissue sialylation in DMRV/hIBM mice is efficiently increased by Ac 4 ManNAc, a synthetic compound. Conclusion: Ac 4 ManNAc rescued muscle phenotype in DMRV/hIBM more efficiently than natural compounds. Significance: Application of this compound includes its potential use in therapy and in understanding the molecular basis of sialic acid deficiency in disease.

SUMMARYRecent reports have demonstrated that circulating endothelial cells (CECs) are observed in several diseases with vascular injury. Because Kawasaki disease (KD) is one type of systemic vasculitis, we hypothesized that an increased number of CECs may be associated with the appearance of complicated coronary artery lesions (CAL). In the present study we investigated the enumeration and origin of CECs in 20 patients with KD, using an immunohistochemical method with monoclonal antibodies: clone P1H12 against ECs and clone AC133 against endothelial progenitor cells (EPCs), which were derived from the bone marrow. The mean number of CECs increased significantly ( P < 0·05) from the acute through the subacute phases of KD compared with both the convalescent phase of KD and healthy children. The mean number of CECs was significantly ( P < 0·05) higher in six KD patients with CAL than in 14 KD patients without CAL. The population of EPCs in the total CECs in KD was 4·4 ± 1·2% (range 0-18%). The number of EPCs during the subacute phase was also significantly higher ( P < 0·05) in KD patients with CAL than in those without CAL. Our findings indicate that the number of CECs increase in KD vasculitis and suggest that the increased numbers of CECs and EPCs may reflect the EC damage of this disease.

SUMMARYCirculating polymorphonuclear neutrophils (PMNs) are known to increase in number and are functionally activated in the acute phase of Kawasaki disease (KD). In the present study, we investigated whether the apoptosis of PMNs is deregulated in KD. When the isolated PMNs were cultured in vitro, the proportions of spontaneous apoptotic PMNs (annexin V 1 cells and cells with fragmented DNA) were found to be significantly lower (P , 0´01) in the patients with KD (n 25) than in the patients with a bacterial infection (n 20) or a viral infection (n 20), or in healthy children (n 20). The proportion of circulating Fas-positive PMNs was also significantly lower (P , 0´01) in the acute KD patients than in the other groups. In the acute phase of KD, the proportion of spontaneous apoptotic PMNs showed a significant positive correlation (P , 0´01) with the proportions of circulating Fas-positive PMNs. Furthermore, the agonistic anti-Fas MoAb (CH-11) induced a significant increase in the proportion of apoptotic PMNs in the patients with a viral infection and healthy children, but not in either the patients with KD or the patients with a bacterial infection. In the intracellular expression of anti-and pro-apoptotic proteins, the A1/Bax ratio was significantly higher in acute KD than in the other groups. These findings indicate that PMN apoptosis is inhibited during the acute phase of KD and also suggest that both the resistance against the Fas-mediated death signal and the down-regulation of the mitochondrial apoptotic signalling pathway due to an altered balance of Bcl-2 protein expression are responsible for the delayed PMN apoptosis.