Retinoic acid receptors (RARs) are ligand-activated nuclear transcription factors that belong to the steroid-thyroid hormone receptor superfamily. We have used the transient transfection of a retinoic acid-responsive reporter plasmid (RARECAT) to investigate the potential interactions between the retinoic acid (RA) and cAMP signaling pathways. Cotransfections of expression plasmids for the catalytic (C) subunits of cAMP-dependent protein kinase with RARECAT showed ligand-independent activation in both CV-1 and HeLa cells and a further 2-fold increase in RARECAT activity in the presence of RA. In CV-1 cells, cotransfections of the expression plasmids for RAR and the C-subunits produced increases in RARECAT activity (12- and 8-fold in the absence of ligand and 21- and 15-fold in the presence of RA for the C alpha- and C beta-isoforms, respectively). Cotransfections of both the C beta-subunit and RAR expression plasmids in HeLa cells produced 22- and 114-fold increases in RARECAT activity in the absence and presence of RA, respectively. These results provide evidence to suggest that the RA and cAMP signaling pathways are coupled, and signaling cross-talk may occur through the direct phosphorylation of RARs by the C-subunit as indicated by in vitro phosphorylation of the receptor.

The first step in retinoid action is binding to their nuclear receptors. Therefore, characterization of binding characteristics of retinoids is of major importance. Human retinoic acid receptors alpha (hRAR alpha), hRAR beta, and mouse RAR gamma (mRAR gamma) were expressed heterologously in Escherichia coli as a recombinant glutathione S-transferase (GST) fusion protein. The expressed fusion proteins were functional and bound specifically to the all-trans-retinoic acid (RA). The dissociation constants (Kd) for RA were 1.4 nM for GST-hRAR alpha, 1.4 nM for GST-hRAR beta, and 3.3 nM for GST-mRAR gamma, respectively. The fusion proteins were further used for competitive displacement assays to determine the displacement constant (DC50) for other selected retinoids. All-trans-RA and 4-oxo-all-trans-RA have high affinity with all three receptors (DC50 = 0.8-55 nM). The 13-cis RA binds to hRAR alpha with low affinity, but not to other RARs evaluated here. All-trans-N-ethylretinamide, all-trans-retinylacetate, and an ethyl ester of tetrahydronaphthalene derivative had no affinity to any RARs. The hRAR alpha and mRAR gamma receptors did not bind a naphthalene carboxylic acid derivative of RA, but hRAR beta binds this chemical with high affinity. Results indicated that the three recombinant proteins were functional in binding various RA congeners. The affinity and binding data of these retinoids were compared to their observed teratogenic activity.

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Background and Objectives: Biliary cast syndrome, which was first reported in 1975, is a rare disease that occurs after liver transplantation. The incidence is even lower in patients who have not undergone liver transplantation. This study reports a rare case of biliary cast syndrome with cholangiocarcinoma-like lesions in a patient who did not undergo liver transplantation. Case Report: Herein, we report a case of a 69-year-old man with right upper quadrant pain and elevated levels of alkaline phosphatase and gamma-glutamyl transferase, who had a history of total gastrectomy for gastric cancer and laparoscopic cholecystectomy for acute cholecystitis. Computed tomography (CT) revealed longitudinal bile stones in the extrahepatic and intrahepatic bile ducts and abrupt narrowing of the left main bile duct accompanied by a narrowing of the upstream bile duct in the left lobe of the liver. Based on the CT findings, the removal of the bile stones in the bile duct and additional examinations of the suspected cholangiocarcinoma were performed. The patient’s symptoms improved, and examinations for suspected cholangiocarcinoma showed no abnormal findings, and he was discharged one month later. Conclusions: The purpose of this case report is to share a rare case of Biliary Cast Syndrome (BCS) occurring without liver transplantation. Additionally, the report aims to share image findings that mimic cancer in BCS, with the goal of reducing unnecessary repetitive biopsies, minimizing patient discomfort, and decreasing unnecessary costs by aiding in the diagnosis of BCS.