Coupling of the thrombin receptor to G12 may account for selective effects of thrombin on gene expression and DNA synthesis in 1321N1 astrocytoma cells.

In 1321N1 astrocytoma cells, thrombin, but not carbachol, induces AP-1-mediated gene expression and DNA synthesis. To understand the divergent effects of these G protein-coupled receptor agonists on cellular responses, we examined Gq-dependent signaling events induced by thrombin receptor and muscarinic acetylcholine receptor stimulation. Thrombin and carbachol induce comparable changes in phosphoinositide and phosphatidylcholine hydrolysis, mobilization of intracellular Ca2+, diglyceride generation, and redistribution of protein kinase C; thus, activation of these Gq-signaling pathways appears to be insufficient for gene expression and mitogenesis. Thrombin increases Ras and mitogen-activated protein kinase activation to a greater extent than carbachol in 1321N1 cells. The effects of thrombin are not mediated through Gi, since ribosylation of Gi/Go proteins by pertussis toxin does not prevent thrombin-induced gene expression or thrombin-stimulated DNA synthesis. We recently reported that the pertussis toxin-insensitive G12 protein is required for thrombin-induced DNA synthesis. We demonstrate here, using transfection of receptors and G proteins in COS-7 cells, that G alpha 12 selectively couples the thrombin receptor to AP-1-mediated gene expression. This does not appear to result from increased mitogen-activated protein kinase activity but may reflect activation of a tyrosine kinase pathway. We suggest that preferential coupling of the thrombin receptor to G12 accounts for the selective ability of thrombin to stimulate Ras, mitogen-activated protein kinase, gene expression, and mitogenesis in 1321N1 cells.

Influence of age on the clinical presentation of acute biliary tract disease.

The influence of age on the presenting manifestation of acute biliary tract disease was evaluated by retrospective review of all cases in which this diagnosis was confirmed at operation over a 30-month period. Results indicated that acute biliary tract diseases in elderly patients presents in a manner not statistically significantly different from younger patients (p greater than 0.05 for all parameters studied). Although such disorders in the elderly occasionally present in an unusual fashion, the majority of older patients present with abnormalities such as pain, jaundice, fever, and leukocytosis as commonly or even more frequently than younger patients.

Mediastinal Hodgkin's disease.

A group of five patients with Hodgkin's disease, nodular sclerosing in type, localized to the mediastinum (Stage IA) is reported. We believe that this presentation sometimes known as "granulomatous thymoma," warrants management in a manner somewhat different from that of the more common presentations of Hodgkin's disease. Nodular sclerosing Hodgkin's disease involving only the mediastinum affects a younger age group in whom the disease may be asymptomatic. Making the diagnosis may necessitate a thoracotomy, but an attempt should be made to obtain tissue short of thoracotomy, as by mediastinoscopy. An extensive attempt at surgical extirpation is not necessary because the disease is very radiosensitive and radiocurable. The combination of Stage I Hodgkin's disease, nodular sclerosing in form, limited to the mediastinum favors an excellent prognosis.