Fumiko Kishi

Human chymase, an enzyme forming novel bioactive 31-amino acid length endothelins.

We report the novel role of human chymase in the production of bioactive 31-amino acid length endothelins (ETs), which may play a role in allergies and vascular diseases. In the bronchi of asthmatic patients, the vascular tissue in atherosclerosis, and the heart muscle in cardiac hypertrophy, both ET-like immunoreactivity and the accumulation of mast cells significantly increase. Chymase from human mast cells selectively cleaves big ET-1, -2 and -3 at their Tyr31-Gly32 bonds, and produces novel bioactive 31-amino acid length ETs, ETs(1-31), without any further degradation products. However, chymases from other species, human cathepsin G, and porcine alpha-chymotrypsin, degrade big ETs. ETs(1-31) at concentrations between 10(-9) M and 10(-7) M exhibited various contractile potencies in rat tracheae and porcine coronary arteries in a dose-dependent manner. Furthermore, ET-1(1-31) at concentrations between 10(-14) M and 10(-10) M caused a significant increase in the intracellular free Ca2+ concentration. The contractile activity of ETs(1-31) may not be the consequence of conversion to the corresponding ETs(1-21) by phosphoramidon-sensitive ET converting enzyme(s) or other chymotrypsin-type proteases and metallo-endopeptidases, because the contractile activity was not significantly inhibited on treatment with inhibitors of these proteases prior to the addition of ET-1(1-31).

Hemopneumothorax Secondary to Multiple Cavitary Metastasis in Angiosarcoma of the Scalp

We report a case of hemopneumothorax secondary to multiple cavitary metastasis in the angiosarcoma of the scalp in an 86-year-old woman, who died of respiratory failure. At autopsy, multiple cavities were found in both lungs. Histologic specimen of the cavitary metastasis of the lung showed that tumor cells proliferated forming several tubular spaces and these tubular spaces seemed to communicate with the central cyst. These findings suggested that imperfect vessel-like structures of the cavitary metastasis are likely to break down and finally grow up to large thin-walled cavities.

MCI-154 activates the Ca2+-activated K+ channel of vascular smooth muscle cells

The aim of this study was to examine the effects of MCI-154, a new positive inotropic agent with vasodilating properties, on the Ca2+-activated K+ channel (KCa channel) of vascular smooth muscle cells. Cultured smooth muscle cells from a porcine coronary artery were studied using the patch-clamp technique. Extracellular application of 100 microM MCI-154 activated the KCa channel in intact cell-attached patch configurations. In excised inside-out patch configurations, application of 100 microM MCI-154 to the cytosolic side activated the KCa channel directly, suggesting that the Ca2+ sensitivity of the KCa channel itself is modulated. Though extracellular application of 100 microM amrinone, a phosphodiesterase inhibitor, activated the KCa channel in the cell-attached patch configurations, application of 100 microM amrinone to the cytosolic side could not activate the KCa channel in inside-out patch configurations. These results indicate that different from amrinone, MCI-154 can modulate Ca2+ sensitivity of the KCa channel in vascular smooth muscle cells.

Unusual endoscopic findings of gastric neuroendocrine tumor.

Gastric neuroendocrine tumor (NET) is sometimes found as a submucosal tumor on upper gastrointestinal endoscopy. Gastric NET with malignant profile and neuroendocrine carcinoma (NEC) show various forms which are difficult to distinguish from gastric cancer and other disease. We report a case of a cauliflower-shaped NET of the stomach. A 61-year-old man was referred to our hospital with a complaint of abdominal fullness. Upper gastrointestinal endoscopic examination revealed an unusual, whitish cauliflower-shaped tumor that belongs to Borrmann type I on the lesser curvature of the gastric antrum. Histological examination of the biopsy specimen revealed NET G2, because the tumor cells were CD56- and synaptophysin-positive by immunohistochemical analysis. A distal gastrectomy with D2 lymphadenectomy was performed. A recurrence in the liver was revealed by follow up computed tomography after 11 months from operation. Combined chemotherapy with irinotecan (CPT-11) plus cisplatin (CDDP) was treated. The patient achieved a partial response, but he died after 31 months from gastrectomy. There is no independent, large-scaled prospective study and no standard treatment for gastric NETs with distant metastases. Our case is reported with a literature review of the treatment of metastatic gastric NET G2.

Source Localization of Initial QRS Vector in Patients with Idiopathic Cardiomyopathy: Comparison with Normal Subjects and Patients with Anterior Myocardial Infarction

The magnetocardiographic three-dimensional (3-D) source localization using superconducting quantum interference device (SQUID) gradiometer has an excellent spatial and temporal resolution. Abnormal Q wave is frequently seen in the electrocardiogram (ECG) in patients with idiopathic cardiomyopathy, even in those without myocardial infarction. In the present study, to assess the origin of abnormal Q wave in the idiopathic cardiomyopathy, current sources were analyzed by the magnetocardiograms (MCGs), and the results were to that of compared with abnormal Q wave in patients with anterior myocardial infarction.

Analysis of Electromotive Force by Magnetocardiogram - Is the Origin of Initial QRS Force (Septal Vector) of Electrocardiogram Intraventricular Septum?

Since the original investigations of Lewis and Rothscnchild (1915) [1], septal activation has been thought to occur first on the Ieft septal surface and thcreafter to spread form the left side to the right side of the intraventricular septum. Thus, the initial QRS vector in electrocardiogram is considered to bedueto activation of intraventricular septum and calledas septal vector. Atlhis time (within 20 msec from the onset of the QRS wave), posterobasal area is not activated. However, normal septal vector disappears in cases of inferior infarction as well as anteroseptal infarction. Thenarises the question whether the initial QRS vector is really composed of intraventricular septum alone. Therefore, we studied the origin of initial QRS forceby magnetocardiogram. The magnetocardiographic three-dimensional (3-D) source localization using supcrconducting quantum interference device (SQUID) gradiometer has an excellent spatial and temporal resolution. To assess electrocardiographic origin of the infarction vector (abnormal Q vector), the magnetocardi ograms of normal subjects and the patients with inferior myocardial infarction (MI) were recorded in an rf-shidded room using biomagnetic measuring system. We also studied the change ofthe initial QRS vectors in left ventricular hypertrophy. The results ofthe study provide anew interpretation of ECG wave forms.