Yasuhiro Katsube

Silent Myocardial ischemia in Kawasaki disease : Evaluation of percutaneous transluminal coronary angioplasty by dobutamine stress testing

BACKGROUNDnMyocardial ischemia and myocardial infarction are the most serious complications of coronary artery lesions in children with Kawasaki disease (KD). Therefore, early detection and treatment of myocardial ischemia in patients with KD is essential. We studied the effectiveness of percutaneous transluminal coronary angioplasty (PTCA) in patients with silent myocardial ischemia detected by dobutamine stress 99mTc myocardial scintigraphy (TMS), body surface mapping (BMS), and signal-averaged ECG late potentials (ELP).nnnMETHODS AND RESULTSnEight of 76 asymptomatic patients with a coronary stenosis >25% and a positive dobutamine stress test were considered to have silent myocardial ischemia. All eight patients had >95% stenoses demonstrated by coronary angiography (CAG) just before PTCA. After PTCA, CAG showed that all of the coronary artery stenoses had been reduced to <50%. Additionally, intravascular ultrasonography (IVUS) performed in five patients before and after PTCA demonstrated adequate dilation of the coronary stenosis after PTCA. All eight patients underwent dobutamine stress TMS, BMS, and ELP 2 to 3 months after PTCA, which demonstrated no regions of myocardial ischemia. Approximately 6 months later, CAG was performed in all eight patients, and only one patient had developed restenosis.nnnCONCLUSIONSnPTCA effectively dilates stenotic coronary arteries in children with KD. Moreover, dobutamine stress TMS, BMS, and ELP are useful for detecting silent myocardial ischemia and estimating the effectiveness of PTCA. Furthermore, IVUS is useful for evaluating the severity of coronary artery lesions before and after PTCA in patients with KD.

The role of the large-conductance voltage-dependent and calcium-activated potassium (BKCa) channels in the regulation of rat ductus arteriosus tone

The role of large-conductance voltage-dependent and calcium-activated potassium (BKCa) channels in the regulation of ductus arteriosus (DA) tone is not clear. This study aimed to examine whether BKCa α and β subunits and BKCa currents are present in the rat DA, as well as whether the BKCa channels are involved in O2-induced ductal constriction. BKCa α and β subunit transcripts (mRNAs) were detected in the DA from premature (19D) and mature (21D) rat fetuses and full-term neonates (NB) by quantitative real-time PCR. The amount of BKCa α mRNAs decreased with advancing development. β1 was the dominant β subunit in the DA, and the amount of β1 mRNAs was greatest in the mature DA. Immunofluorescence staining showed that the majority of BKCa α and β1 proteins were colocated with alpha smooth muscle actin (α-SMA) in the tunica media of the DA in all age groups. The protein expression of the α subunit was greatest in the mature DA, while the expression of the β1 subunit did not differ among all three groups. The 19D and 21D ductus tensions were recorded under various conditions by myograph. The 19D ductus rings exhibited poor O2 sensitivity and no response to BKCa inhibitor (paxilline) or activator (NS1619). The 21D ductus rings developed significant constriction induced by O2. Paxilline did not increase the 21D DA tension under either hypoxic or oxygenated conditions. NS1619 dilated the 21D DA only under oxygenated conditions. The recorded BKCa currents were greatest in the 21D DA smooth muscle cells (SMCs) upon using a whole-cell patch clamp. Our study indicated that BKCa channels exist in the DA but are not involved in O2-induced ductal constriction. Activation of BKCa channels led to vasodilatation in the preconstricted DA induced by O2, possibly suggesting a way to maintain the patency of DA after birth.

Carbachol inhibition of Ca2+ currents in ventricular cells obtained from neonatal and adult rats

We investigated the postnatal developmental changes produced by the muscarinic receptor agonist, carbachol, on the L-type Ca2+ current (ICa(L)) in neonatal (aged 5 to 7 days) and adult (aged 2 to 5 months) rat ventricular cells by using the whole-cell voltage clamp technique. Carbachol inhibited the isoproterenol-stimulated ICa(L). The maximal inhibition was 89.3 +/- 4.8% (n = 5) in neonatal cells and 17.7 +/- 7.7% (n = 9) in adult cells. Carbachol inhibited the forskolin-stimulated ICa(L) to almost same extent as the isoproterenol-stimulated ICa(L). In the cells pretreated with pertussis toxin, carbachol failed to inhibit the isoproterenol-stimulated ICa(L), indicating that carbachol produced its effect via a pertussis toxin-sensitive G-protein pathway. The effects of carbachol in adult cells became more pronounced, increasing from 17.7% to 54.8% (n = 11), with the addition of the synthetic inhibitory G-protein alpha subunit (Gi alpha) (1 microM) to the reaction. Conversely, the alpha subunit of another pertussis toxin-sensitive synthetic G-protein (G(o) alpha, 1 microM) failed to mimic the effect of Gi alpha. These results suggest that, in rat ventricular cells, (1) the action of carbachol on ICa(L) showed a marked decrease during development; (2) the decrease in the effect of carbachol in adult cells is in part due to a decrease in the activity of pertussis toxin-sensitive G protein, especially Gi alpha.

Infantile Acute Monocytic Leukemia with Tumor Formation in the Skin Expressing Adhesion Molecules as seen by Electronmicroscopy

We report a case of infantile acute monocytic leukemia associated with solid tumors in the skin. Light microscopy showed that the tumor cells were mainly spindle-shaped and arranged in tandem. Immunohistochemical staining showed that fibronectin was detected in the extracellular matrix (and partially on the surface of tumor cells), integrin alpha 5 beta 1 on the cell surface, and vinculin and actin were detected in the cytoplasm of the tumor cells. Electron microscopy showed that the tumor cells had perpendicular transmembranous fibrils and closely situated collections of cytoplasmic microfilaments beneath the cell membrane suggesting fibronexus-like structures. We conclude that the expression of fibronectin, integrin alpha 5 beta 1, vinculin, cytoplasmic actin and fibronexus-like structure in leukemic cells indicate these cells possess an adhesive function. The mechanism of formation of the extramedullary solid tumors in this patients involved these adhesion molecules of the tumor cells.