The role of protein kinase C in muscarinic agonist-induced insulin release from rat insulinoma cells was investigated. The dose-dependent stimulation of insulin secretion by carbamylcholine (carbachol) was associated with dose-dependent increase in the release of 3H-inositolphosphates from prelabeled rat insulinoma cell line (RINr) cells. After preincubation with 32P-orthophosphates, carbachol also evoked a rapid decrease in 32P-labeling of phosphatidylinositol-4,5-bisphophate with concomitant increase in 32P-labeling of phosphatidic acid. Furthermore, carbachol significantly increased membrane-associated protein kinase C activity with a simultaneous decrease of its activity in cytosol. Although phorbol-12,13-dibutyrate (PDBu), a protein kinase C activator, also stimulated insulin release, insulin secretion induced by concomitant administration of carbachol and PDBu was clearly less than the level expected on the basis of an additive action. Moreover, PDBu significantly inhibited inositolphospholipid turnover stimulated by carbachol. Finally, PDBu inhibited the binding of 3H-scopolamine binding revealed that PDBu decreased the number of muscarinic receptors without altering its affinity. These findings suggest that activation of protein kinase C not only mediates muscarinic stimulation of insulin secretion from RINr cells but also operates a negative feedback mechanism in a signal transduction system, at least in part, via down-regulation of muscarinic receptors.

No abstract

Acute cholangitis due to impacted bile duct stone is sometimes fatal and require prompt bile duct decompression. Particularly, AOSC (acute obstructive suppurative cholangitis) is the most serious form of bacterial cholangitis and its prognosis is ususally very poor when treated conservatively. We have been treated impacted bile duct stones by decompressing the duct endoscopically. Here, we report the characteristics of our elderly patients with impacted bile duct stones who received urgent decompression treatment mainly by endoscopic techniques. In the endoscopical traetment group, the number of patients with AOSC was 5 out of 46 AC (acute cholangitis) patients (11%) under 69 years old, 14 out of 52 (27%) from 70 to 79 years old, and 12 out of 28 (43%) over 80 years old. Obviously, the severity of acute cholangitis (ratio of AOSC to AC) was higher in the elderly. This tendency was similar to the patients who received urgent transhepatic decompression treatment, although they were small in number. In all the patients treated, 7 were classified into the most serious AOSC category with Reynolds'sign, and notably 6 out of 7 were over 70 years old. More strikingly, 5 of 7 patients were over 80, and their mortality rate was indeed high. Thus, in the elderly, bacterial cholangitis by impacted bile stones was a very serious condition. Especially, the outcome of AOSC over 80 years old with Reynolds' sign was very poor, in spite of emergency endoscopic treatment.

No abstract

The sonographic textures of 10 parathyroid tumors in nine patients were examined and compared with their histologic features, particularly with the amount of fibrous trabeculae. The carcinomas containing a large amount of fibrous trabeculae, which is the most frequent finding in parathyroid cancer, were very echogenic. On the other hand, the adenomas without fibrous trabeculae showed a low echogenicity. These data suggest that the possibility of malignancy is high when the parathyroid tumor is found to be very echogenic.