Nozomi Yamaguchi

Endothelial dysfunction in adult patients with a history of Kawasaki disease

To assess the existence of endothelial dysfunction and the possibility of the early onset of atherosclerosis in the chronic stage of Kawasaki disease (KD), we examined endothelial function in adult patients late after the onset of KD. We evaluated two age-matched groups: 35 adult KD patients (KD group) (mean age, 27.0xa0years; mean interval time, 24.1xa0years), and 36 healthy adults (control group). To assess vascular endothelial function, flow-mediated dilatation (%FMD) of the brachial artery and urinary nitrites and nitrates (NOx) were examined. We also measured adhesion molecules and several coagulation-fibrinolysis markers. In addition, we measured high-sensitive C-reactive protein (hs-CRP) as a chronic inflammatory marker, and brachial-ankle pulse wave velocity (baPWV) as a marker for arterial stiffness. %FMD was significantly reduced in the KD group when compared with that of the control group (KD group, 10.4u2009±u20092.6%; control group, 14.4u2009±u20093.2%, p<0.05), particularly in patients with coronary artery lesions. Thrombin-antithrombin III complex values were higher in the KD group, although no significant differences were observed in the other markers for endothelial function. Hs-CRP was significantly elevated only in the patients with coronary aneurysms. Furthermore, in the male KD patients, the baPWV values were significantly higher than those in the control subjects. This study revealed that the adult patients with a history of KD had systemic vascular endothelial dysfunction, and also suggested that a history of KD was possibly one of the risk factors for early onset of atherosclerosis.

Mosaic serine proteases in the mammalian central nervous system.

We review the structure and function of three kinds of mosaic serine proteases expressed in the mammalian central nervous system (CNS). Mosaic serine proteases have several domains in the proenzyme fragment, which modulate proteolytic function, and a protease domain at the C-terminus. Spinesin/TMPRSS5 is a transmembrane serine protease whose presynaptic distribution on motor neurons in the spinal cord suggests that it is significant for neuronal plasticity. Cell type-specific alternative splicing gives this protease diverse functions by modulating its intracellular localization. Motopsin/PRSS12 is a mosaic protease, and loss of its function causes mental retardation. Recent reports indicate the significance of this protease for cognitive function. We mention the fibrinolytic protease, tissue plasminogen activator (tPA), which has physiological and pathological functions in the CNS.

cAMP-dependent regulation of spinesin/TMPRSS5 gene expression in astrocytes.

Spinesin/TMPRSS5 is a mosaic type serine protease that is predominantly expressed in the spinal cord. To identify the mechanism of spinesin expression, we investigated its expression in vivo and in vitro using several cell lines. Immunohistochemical and in situ hybridization analyses revealed that mouse spinesin (m‐spinesin) was abundantly expressed in white matter astrocytes. Similarly, we confirmed abundant expression of m‐spinesin in astrocyte cell lines. Then, we analyzed the expression of variant forms of m‐spinesin in these cell lines. Interestingly, a transmembrane type (type 4) variant was expressed in neuroblastoma and astrocyte cell lines, whereas a cytoplasmic type (type 1) variant was specifically expressed in astrocyte cell lines. Furthermore, expression of both variants was up‐regulated by dibutyryl‐cAMP (dbcAMP) treatment only in astrocyte cell lines. We also analyzed the promoter region of the m‐spinesin gene and revealed that the 5′‐flanking region from base pairs −224 to −188 was essential for cAMP‐dependent regulation of its transcription. These results indicate that m‐spinesin is involved in the function of astrocytes in the spinal cord and that there may be astrocyte‐specific regulation of its gene expression.

Mice lacking motopsin/PRSS12 gene showed abnormal social behavior

The relationship between parents and children is one of the most important social relationships. We hypothesized that the emotional facial recognition between parents and children would induce specific neural activities. Ten pairs of mothers and their own adulthood daughters saw and judged on their happy, neutral and anger facial expressions each other during fMRI. Seven pairs of female friends received same procedure. The recognition of familial faces induced brain activities in the anterior paracingulate cortex, posterior cingulate cortex and bilateral posterior superior temporal sulcus (pSTS) while the recognition of friend’s faces induced brain activities in the right pSTS. When daughters saw their own mothers’ anger faces, the subgenual prefrontal cortex (sgPFC) deactivated compared to neutral faces. This deactivation was observed neither in mothers nor in friends. These results suggest that the sgPFC of children play a specific role in the anger facial recognition of parents.