Keiko Kaihara

IgG anti-laminin-1 autoantibody and recurrent miscarriages.

PROBLEM: The present study assesses the clinical significance of anti‐laminin‐1 auto‐antibodies (auto‐Abs) in recurrent miscarriages.
 METHOD OF STUDY: A total of 207 recurrent aborters with a history of two or more consecutive first‐trimester miscarriages were tested for the presence of anti‐laminin‐1 Abs, β2‐glycoprotein I‐dependent anticardiolipin Abs, lupus anticoagulants, anti‐DNA Abs, and anti‐nuclear Abs, before they had conceived again. Recurrent aborters then were followed up during subsequent pregnancies and their outcomes were evaluated relative to their blood test results prior to pregnancy.
 RESULTS: Fifty‐five (31.1%) women out of 177 recurrent aborters were positive for IgG anti‐laminin‐1 auto‐Abs. The levels of IgG anti‐laminin‐1 auto‐Abs in recurrent aborters were significantly higher than those in healthy pregnant women and in healthy non‐pregnant women (P=0.0043 and 0.0073, respectively). The live birth rate of subsequent pregnancies in IgG anti‐laminin‐1 auto‐Abs‐positive recurrent aborters was significantly lower than the IgG anti‐laminin‐1 auto‐Abs‐negative recurrent aborters (P=0.0320). There were no specifically significant relationships observed between IgG anti‐laminin‐1 auto‐Abs and other tested auto‐Abs.
 CONCLUSION: IgG anti‐laminin‐1 auto‐Abs are associated with recurrent miscarriages and the subsequent pregnancy outcome of recurrent aborters.

Effects of axial stretch on sarcolemmal BKCa channels in post‐hatch chick ventricular myocytes

We have previously reported the electrophysiological properties of sarcolemmal stretch‐activated BKCa (SAKCA) channels cloned from cultured chick embryonic ventricular myocytes. However, the role of BKCa channels in the electrophysiology of the more mature heart is not clear. We have investigated the effects on the BKCa current of axial stretch in post‐hatch ventricular myocytes. Whole‐cell currents of ventricular myocytes isolated from 2‐week‐old chicks were recorded using the patch‐clamp technique, while the cells were either held at resting length or stretched to cause a 10% increase in sarcomere length using a pair of carbon fibres attached to opposite ends of the cell. Stretch did not affect whole‐cell currents immediately after the stretch was applied. However, sustained stretch for 3 min significantly increased outward currents. This stretch‐induced change was reversed by applying 10 nm iberiotoxin, a specific BKCa channel blocker, or a Na+–Ca2+‐free environment. These results were reproduced in a computer simulation study. The present study is the first report about the sarcolemmal BKCa current from post‐hatch ventricular myocytes. The present results suggest that axial stretch activates BKCa channels via a stretch‐induced increase in the cytosolic Na+ concentration followed by an increased Ca2+ influx.

Effect of azelnidipine and amlodipine on single cell mechanics in mouse cardiomyocytes

Azelnidipine and amlodipine are dihydropyridine-type Ca(2+) channel blockers for the treatment of hypertension. Although these drugs have high vasoselectivity and small negative inotropic effects in vivo, little is known regarding their direct effects on cellular contractility without humoral regulation or the additive effects of these drugs with other antihypertensive drugs on myocardial contractility. To investigate the effects of Ca(2+) channel blockers on single cell mechanics, mouse cardiomyocytes were enzymatically isolated, and a pair of carbon fibers was attached to opposite cell-ends to stretch the cells. Cells were paced at 4 Hz superfused in normal Tyrode solution at 37°C. Cell length and active/passive force calculated from carbon fiber bending were recorded in 6 different preload conditions. Slopes of end-systolic force-length relation curves (maximum elastance) were measured as an index of contractility before and after drugs were administered. Azelnidipine at 10nM and 100 nM did not change maximum elastance, while amlodipine at 100 nM did decrease maximum elastance. The combination of RNH-6270 (active form of angiotensin II receptor blocker, olmesartan, 10nM) and either amlodipine (10nM) or azelnidipine (10nM) did not affect maximum elastance. Although both amlodipine and azelnidipine can be used safely at therapeutically relevant concentrations even in combination with olmesartan, the present results suggest that azelnidipine has a less negative inotropic action compared to amlodipine.