We have established an in vitro model of airway hyperresponsiveness, using a bovine tracheal smooth muscle cell (BTSMC)‐embedded collagen gel lattice. When the gel was pretreated with lysophosphatidic acid (LPA), which activates the small G protein RhoA, ATP‐ and high K+ solution‐induced gel contraction was significantly augmented. This was not due to the modulation of Ca2+ mobilizing properties, since ATP‐ and high K+‐induced Ca2+ transients were not significantly different between control and LPA‐treated BTSMC. Y‐27632, an inhibitor of Rho‐kinase, suppressed the LPA‐induced augmentation of gel contraction, whereas it did not inhibit the contraction of control gels. Theophylline (> 1 μm) reversed the LPA‐induced augmentation of gel contraction, whereas it inhibited control gel contraction only with a very high concentration (100 μm). We confirmed that theophylline increased the intracellular concentration of cAMP ([cAMP]i) in BTSMC. Elevation of [cAMP]i with dibutyryl cAMP or forskolin also reversed the LPA‐induced augmentation of gel contraction. Furthermore, theophylline, as well as dibutyryl cAMP and forskolin, suppressed the LPA‐induced membrane translocation of RhoA, indicating that they prevented airway hyperresponsiveness by inhibiting RhoA. We conclude from these results that theophylline inhibits LPA‐induced, RhoA/Rho‐kinase‐mediated hyperresponsiveness of tracheal smooth muscle cells due to the accumulation of cAMP.
The RA anastomosed to the aorta appears to have good long-term outcomes, similar to the RITA as the second arterial graft. Furthermore, the choice of RA avoids sternal complications and shortens the operation time compared to the use of BITA.
A 47-year-old man died from fatal pulmonary hemorrhage. Cardiac angiosarcoma with lung metastases was found at postmortem examination. His chest radiograph showedbilateral, diffuse nodular infiltrates without cardiomegaly. Nocardiac signs and symptomswere observed. The clinical outcome was rapidly fatal. Angiosarcoma of the heart should be suspected in patients with hemoptysis and nodular chest radiograph abnormalities, even in the absence of cardiac signs and symptoms. (Internal Medicine 36: 191-193, 1997)
In patients with three-vessel coronary artery disease, CABG is associated with better survival and less revascularization than PCI using 2nd DES at mid-term results.
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