Endothelial function and coronary spastic angina

Coronary spasm plays an important role in the pathogenesis of not only variant angina but also coronary heart disease in general including acute coronary syndromes, especially in the Japanese population. The vascular endothelium has been reported to be a multifunctional organ whose integrity is essential for normal vascular physiology. Vascular endothelial dysfunction can be a critical factor in the pathogenesis of ischemic heart disease. Acetylcholine and methacholine cause vasodilation by endothelium-derived relaxing factor when the endothelium is functioning normally, whereas they cause vasoconstriction when the endothelium is removed or damaged. Coronary spasm can be induced by a variety of stimuli with different mechanisms of action, including acetylcholine and methacholine. Patients with coronary spasm may have a disturbance in endothelial function as well as local hyperreactivity of the coronary arteries.     

A case of primary pleural leiomyosarcoma]

A 70-year-old man was admitted to our hospital with complaints of chest pain and exertional dyspnea. Chest radiography and computed tomography (CT) revealed right pleural effusion and pleural thickening on admission. The pleural fluid was bloody. Microbiological and cytologic examinations of the fluid were negative. The chest CT revealed progress of pleural thickening after hospitalization. A thoracoscopic pleural biopsy was performed, and the histological finding of the excised specimen was leiomyosarcoma. Because no organ of origin of the leiomyosarcoma, other than the pleura, was detected, this case was diagnosed as a primary pleural leiomyosarcoma. It is thought that leiomyosarcoma originating from the pleura is rare.     

Cardiac sarcoplasmic reticulum chloride channels regulated by protein kinase A.

In heart cells, several plasma membrane ion channels are targets for phosphorylation. However, it is not known whether sarcoplasmic reticulum (SR) ion channels, which are also essential in the regulation of cardiac function, are regulated by second-messenger systems. Here, we show that a Cl- channel in the cardiac SR membrane is activated by the catalytic subunit of protein kinase A (PKA). Purified cardiac heavy SR vesicles were incorporated into planar lipid bilayers. This channel spontaneously inactivated within a few minutes after the channel was incorporated into the bilayer. Mg-ATP (2-5 mM), but not the nonhydrolyzable ATP analogue 5'-adenylylimidodiphosphate, added to the cis solution prevented this spontaneous channel inactivation. After the inactivation process occurred, the catalytic subunit of PKA (with 0.05 mM Mg-ATP) reactivated this channel. These effects of Mg-ATP and PKA on the Cl- channel were prevented by an inhibitor of PKA. Thus, these results suggest that this SR Cl- channel is a novel target of PKA-dependent phosphorylation in cardiac muscle regulation.     

A new method for measurement of blood flow,pH, and transmucosal potential difference in rat gastroduodenal mucosa by endoscopy

A method was developed to measure the mucosal blood flow (BF), mucosal pH (pH), and transmucosal potential difference (PD) in various sites from the oral cavity to the duodenum without surgical operation or damage to the subject rats. These measurements were carried out by using three indicator electrodes, which were attached to the various sites through the suction channel of an endoscope. The hydrogen gas clearance method was used for the measurement of BF. BF values obtained at the fundic, pyloric, and duodenal regions were 119±17, 69.9±8.8, and 114±18 ml/min/100 g (mean±se), respectively. The pH values were lowest at the cardiac portion and the forestomach and highest at the duodenum. PD showed higher values at the stomach and lower values at the pharynx and duodenum. Using this technique, it was possible to measure the BF, pH, and PD repeatedly and safely at various sites in the same rat. Therefore, it was suggested that this method is useful in studying the physiological functions of the stomach and duodenum and the pathogenesis of gastroduodenal ulceration and that this method is applicable to measure the change of the above parameters in the healing process of gastric ulcer in rats.     

Interleukin-1 accelerates autocrine growth of myeloma cells through interleukin-6 in human myeloma

Recombinant interleukin 1 alpha (rIL-1 alpha) augmented proliferation of freshly isolated myeloma cells as well as B-cell stimulatory factor 2 (BSF-2)/interleukin-6 (IL-6). Recombinant IL-1 alpha-induced proliferation was partially inhibited by anti-IL-6 antibody. In the culture supernatants of rIL-1 alpha-stimulated myeloma cells, IL-6 activities, which were measured by using an IL-6-dependent murine hybridoma clone, MH60.BSF2, were increased, when compared with those in the culture supernatants of nonstimulated myeloma cells. Furthermore, IL-6 messenger RNA (mRNA) expression was also augmented in IL-1 alpha- stimulated myeloma cells. Therefore rIL-1 alpha stimulates myeloma cells to produce IL-6, which consequently augments proliferation of myeloma cells. Thus, IL-1 can accelerate autocrine growth of myeloma cells through IL-6.     

Decrease in BSF-2/IL-6 response in advanced cases of multiple myeloma

Human myeloma cells freshly isolated from 40 patients with IgG multiple myeloma (MM, 10 in stage I and 30 in stage III), were cultured for 48 hours with recombinant B cell stimulatory factor 2 (rBSF-2)/interleukin- 6 (IL-6), which is considered a major growth factor for myeloma cells. Uptake of 3H-thymidine by these purified myeloma cells was measured, and BSF-2 response was evaluated by stimulation index and delta cpm induced by rBSF-2. Myeloma cells from cases in stage I responded to rBSF-2 better than those in stage III. Moreover rBSF-2 responders also showed better response to chemotherapy. Therefore, these results suggest that in vitro response of myeloma cells to BSF-2 correlates with disease progression and clinical response in patients of MM.     

Treatment strategy for Boerhaave''s syndrome

Esophageal rupture is a potentially mortal condition. Rapid and correct diagnosis, and urgent surgical treatment with esophagectomy is indicated, but conservative and other surgical treatments have also been reported recently. The treatment strategies for esophageal rupture are discussed here, based on our experiences with four cases during the last 10 years. They were admitted urgently and each was treated by a different method. Three of them underwent emergency operations, one undergoing primary closure of the ruptured esophagus, another received a T-tube insertion from the ruptured site with omental flap, and the third an esophagogastrectomy. The fourth case was treated conservatively. All patients survived and were discharged 36-144 days post treatment. One of them was readmitted for debridement of necrotic rib. In conclusion, the prompt and accurate diagnosis of esophageal rupture is crucial for a subsequent successful treatment. Conservative treatment or operation including esophagectomy will be determined by the severity of the condition.     

Effect of ethanol on endothelin-1 release from gastric vasculature

The effects of ethanol on gastric vasculature in isolated vascularly perfused rabbit stomach was investigated. The isolated stomach was perfused with Krebs-Henseleit solution containing 3% dextran bubbled with 95% O₂ and 5% CO₂ at a rate of 12 ml/min. After mixture and perfusion of 10 mM to 400 mM of ethanol, perfusion pressure and endothelin-1 concentration in effluent from gastric vasculature were measured. Perfusion pressure and endothelin-1 concentration in effluent increased in a dose-dependent manner with increasing ethanol concentrations. In conclusion, the data suggest that ethanol may stimulate the release of endothelin from gastric vasculature and may cause gastric ischemia due to vasoconstriction resulting in acute gastric mucosal injury.