No abstract

Immunohistochemical and morphometrical studies were performed to elucidate the specificity of atherosclerosis in the descending branch (the segments 5 and 6) of the left coronary artery associated with acute myocardial infarction (AMI) in the anterior wall of the heart and non-insulin-dependent diabetes mellitus (NIDDM). The NIDDM without AMI group showed diffuse intimal thickening with smooth muscle cells, combined with much more intense immunostaining of tenascin than the non diabetic groups. The AMI without NIDDM group showed atheromatous thickening with decreased smooth muscle cells, a large number of macrophage and TUNEL-positive cells compared with the groups without AMI. However, the AMI with NIDDM group revealed atherosclerotic lesion with decreased smooth muscle cells, increased macrophages and TUNEL positive cells associated with the increased localization of tenascin and TGF-beta1 compared with the control. These findings suggest that the specificity of coronary atherosclerosis in diabetic patients may be the extensive atherosclerotic changes associated with increased tenascin. In AMI with NIDDM, increased TGF beta1 may induce apoptosis in the atheroma and coronary dysfunction, contributing to the development of acute myocardial infarction.

Macroscopic and unitary currents through Ca2 § CI-channels were examined in enzymatically isolated guinea-pig hepatocytes using wholecell, excised outside-out and inside-out configurations of the patch-clamp technique. When K + conductances were blocked and the intracellular Ca 2+ concentration ([Ca2+]i) was set at 1 p,M (pCa--6), membrane currents were observed under whole-ceU voltage-clamp conditions. The reversal potential of the current shifted by ~60 mV per 10-fold change in the external CI-concentration. In addition, the current did not appear when CI-was omitted from the internal and external solutions, indicating that the current was CI-selective. The current was activated by increasing [Ca2+]i and was inactivated in Ca2+-free, 5 mM EGTA internal solution (pCa > 9). The current was inhibited by bath application of 9-anthracenecarboxylic acid (9-AC) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) in a voltage-dependent manner. In single channel recordings from outside-out patches, unitary current activity was observed, whose averaged slope conductance was 7.4 -0.5 pS (n = 18). The single channel activity responded to extracellular CI-changes as expected for a CI-channel current. The open time distribution was best described by a single exponential function with mean open lifetime of 97.6 -+ 10.4 ms (n = 11), while at least two exponentials were required to fit the closed time distributions with a time constant for the fast component of 21.5 -2.8 ms (n = 11) and that for the slow component of 411.9 _ 52.0 ms (n = 1 I). In excised inside-out patch recordings, channel open probability was sensitive to [Ca2+]i . The relationship between [Ca2+]i and channel activity was fitted by the Hill equation with a Hill coefficient of 3.4 and the half-maximal activation was 0.48 p,M. These results suggest that guinea-pig hepatocytes possess Ca 2+-activated CI-channels.Dr. Koumi's present address is the

PTT may be a useful parameter for evaluating arterial oxygenation in patients with chronic liver disease with early HPS.

Chymase, one of the proteases contained in human mast cells, promotes myocardial and renal interstitial fibrosis by converting angiotensin I to II (AII). We previously established a method for measuring chymase in liver tissue and examined the relationship between chymase and fibrosis in chronic hepatitis. In the present study, chymase was determined in liver specimens affected by autoimmune hepatitis (AIH, n=10) or primary biliary cirrhosis (PBC, n=12). To investigate spatial relationships between hepatic fibrosis and human chymase, mast cell distribution in the specimens was determined immunohistochemically using anti-chymase antibody. The mean amounts of chymase in livers with AIH and PBC were 11.56+/-10.64 and 11.67+/-9.96 ng/mg respectively. Hepatic chymase in AIH and PBC was significantly more abundant than in acute hepatitis (AH, 2.72+/-2.23 ng/mg, n=10; p<0.05). When sections from patients with AIH and PBC were immunostained for chymase, immunoreactive mast cells were detected in portal areas and sinusoidal walls, coinciding with zones of fibrosis. Thus chymase appears to be involved in hepatic fibrosis in AIH and PBC.